56 results on '"Khan, Mansoor A."'
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2. Sampling of organic contaminants from seawater
- Author
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Khan, Mansoor, primary and Akhtar, Farhan, additional
- Published
- 2024
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3. Drug and formulation development processes
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Charoo, Naseem A., primary, Mohamed, Eman M., additional, Eltigani, Mustafa, additional, Khan, Mansoor A., additional, Nutan, Mohammad T.H., additional, and Rahman, Ziyaur, additional
- Published
- 2024
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4. Atom probe tomography of nanomaterials
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Khan, Mansoor A., primary and Zheng, Rongkun, additional
- Published
- 2023
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5. Contributors
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Arsiccio, Andrea, primary, Bermejo, Marival, additional, Camara-Martinez, Irene, additional, Charoo, Naseem A., additional, Chountoulesi, Maria, additional, Demetzos, Costas, additional, Domínguez-Robles, Juan, additional, Douroumis, Dennis, additional, Dynes, Sean, additional, Eltigani, Mustafa, additional, Gazouli, Maria, additional, Gonzalez-Alvarez, Isabel, additional, Gonzalez-Alvarez, Marta, additional, Hejduk, Arkadiusz, additional, Ibrić, Svetlana, additional, Karalis, Vangelis D., additional, Kayalar, Canberk, additional, Khan, Mansoor A., additional, Kompocholi, Eleni, additional, Korelidou, Anna, additional, Krstić, Mirjana, additional, Kuttolamadom, Mathew, additional, Lagopati, Nefeli, additional, Larrañeta, Eneko, additional, Li, Linlin, additional, Lulek, Janina, additional, Magill, Elizabeth R., additional, McIlorum, Victoria J., additional, Medarević, Djordje, additional, Mohamed, Eman M., additional, Nutan, Mohammad T.H., additional, Picco, Camila J., additional, Pippa, Natassa, additional, Pisano, Roberto, additional, Pispas, Stergios, additional, Rahman, Ziyaur, additional, Ruiz-Picazo, Alejandro, additional, Sanchez-Dengra, Barbará, additional, Siermicka, Eliza, additional, Tabriz, Atabak Ghanizadeh, additional, Triantafyllopoulou, Efstathia, additional, Utomo, Emilia, additional, and Vlachou, Marilena, additional
- Published
- 2023
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6. Contributors
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Almqvist, Jessica, primary, Asadi, Amir, additional, Aziz, Qasim, additional, Balardin, Joana Bisol, additional, Ballester, Pedro, additional, Barbeiro, Hermes Vieira, additional, Barbeiro, Denise Frediani, additional, Bekri, Soumeya, additional, Belfort, Rubens, additional, Bergero, Miguel A., additional, Bester, Adri, additional, Bhattacharjee, Gargi, additional, Biazoli, Claudinei Eduardo, additional, Billeci, Lucia, additional, Biude da Silva Duarte, Graziela, additional, Blair, Alex B., additional, Braddick, Darren, additional, Brant, Rodrigo, additional, Britton, Robert A., additional, Burkhart, Richard A., additional, Byrne, J.A., additional, Cabral, Joaquim M.S., additional, Cabral, Thiago, additional, Câmara, José S., additional, Campillo-Artero, Carlos, additional, Castro Guzman, Grover Enrique, additional, Catela Ivkovic, Tina, additional, Cayún, Juan P., additional, Charoo, Naseem A., additional, Chen, Y., additional, Codari, Marina, additional, Correa, Graciely G., additional, Coto-Llerena, Mairene, additional, Couzigou, Patrice, additional, Cozetto, Daniel A., additional, Currie, Gemma, additional, Dalla-Pozza, L., additional, de Jesus, Victor N., additional, de Lara, Zabalo Manrique, additional, Delles, Christian, additional, de Miguel Beriain, Iñigo, additional, de Moura, Juliana, additional, de Paiva, Cintia S., additional, de Souza, Rodrigo G., additional, Detti, Paolo, additional, Díaz, Romina, additional, Ehrenfeld, Jesse M., additional, Faintuch, Bluma Linkowski, additional, Faintuch, Joel, additional, Faintuch, Jacob J., additional, Faintuch, Salomao, additional, Faraldo Corrêa, Telma A., additional, Farmer, Adam D., additional, Freire, Paulo J.C., additional, Fujita, Andre, additional, Garrido, Daniel, additional, Gayatri, Athalye-Jape, additional, Gohil, Nisarg, additional, Gómez de Cedrón, Marta, additional, Gonzalez Moron, Dolores, additional, Ishii, Tetsuya, additional, J. Pirtle, Claude, additional, Jain, Abhishek, additional, Jamieson, R.V., additional, Jiramongkolchai, Kim, additional, Kaiser, Thomas, additional, Kamel Boulos, Maged N., additional, Kanuri, Sri Harsha, additional, Kauffman, Marcelo A., additional, Khambhati, Khushal, additional, Khan, Mansoor A., additional, Kreutz, Rolf P., additional, Kuttolamadom, Mathew, additional, Lal, Hitesh, additional, Lima de Carvalho, Jose Ronaldo, additional, Lins, Milca R.C.R., additional, López-Campos, José Luis, additional, Louis Gehlbach, Peter, additional, Lumbreras, Blanca, additional, Mahajan, Vinit B., additional, Maia, Mauricio, additional, Mani, Indra, additional, Martinez, J. Alfredo, additional, Martinez, Pablo F., additional, Mary, Sheon, additional, Mathur, Tanmay, additional, Miranda, Cláudia C., additional, Mirnezami, Reza, additional, Ng, Charlotte K.Y., additional, Palau, Francesc, additional, Panchasara, Happy, additional, Pandian, Navaneeth K.R., additional, Park, Karen Sophia, additional, Passos, Ives Cavalcante, additional, Pastor-Valero, Maria, additional, Patella, Francesca, additional, Patralekh, Mohit Kumar, additional, Patusco, Lucas Mohr, additional, Pedrolli, Danielle B., additional, Pereira, Jorge A.M., additional, Pesapane, Filippo, additional, Pincelli, João Vitor, additional, Piscuoglio, Salvatore, additional, Ponce-Lorenzo, Jose J., additional, Porto-Figueira, Priscilla, additional, Priyadharshini, V.S., additional, Pushparaj, Peter Natesan, additional, Quiñones, Luis A., additional, Quintanilha, Bruna Jardim, additional, Rahman, Ziyaur, additional, Ramírez de Molina, Ana, additional, Ramos-Lopez, Omar, additional, Ramos, Kenneth S., additional, Rapole, Srikanth, additional, Rebello Pinho, João Renato, additional, Reis, Bruna Zavarize, additional, Rey-Lopez, Juan Pablo, additional, Ribeiro, Nathan V., additional, Rogero, Marcelo Macedo, additional, Roizenblatt, Marina, additional, Roizenblatt, Jaime, additional, Roza, Thiago Henrique, additional, Rozich, Noah S., additional, Ruffle, James K., additional, Sanjay, Patole, additional, Saraiva, Fábio P., additional, Sardanelli, Francesco, additional, Sato, João Ricardo, additional, Schutte, Aletta E., additional, Schwerdtfeger, Luke A., additional, Selahi, Amirali, additional, Sharma, Prakash Chand, additional, Shripada, Rao, additional, Silva, Patrick J., additional, Singh, Vijai, additional, Slaby, Ondrej, additional, Soares, Bruno Araujo, additional, Soriano, Francisco Garcia, additional, Souckova, Kamila, additional, Squizato, Patrick N., additional, Stabellini, Nickolas, additional, Staley, Christopher, additional, Stanke Scandelari, João Paulo, additional, Suter, Matteo B., additional, Sylvester, D.E., additional, Taware, Ravindra, additional, Tebani, Abdellah, additional, Teran, Luis M., additional, Terracciano, Luigi M., additional, Tis, Taleb Ba, additional, Tobet, Stuart A., additional, Tonacci, Alessandro, additional, Toribio-Mateas, Miguel, additional, Tsang, Stephen H., additional, Tsivaka, Dimitra, additional, Tsougos, Ioannis, additional, Vamvakas, Alexandros, additional, Varanini, Maurizio, additional, Vassiou, Katerina, additional, Vatti, Giampaolo, additional, Verma, Renu, additional, Verma, Kalyani, additional, Vittorelli, Luiz Otávio, additional, Volonté, Caterina, additional, von Flüe, Markus, additional, Wafi, Arsalan, additional, Wagatuma Bottolo, Bruna Mayumi, additional, Wei, Qingshan, additional, Zhang, Peng, additional, Zhang, Shengwei, additional, Zhu, Zhigang, additional, and Zimerman, Aline, additional
- Published
- 2020
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7. Printing of personalized medication using binder jetting 3D printer
- Author
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Rahman, Ziyaur, primary, Charoo, Naseem A., additional, Kuttolamadom, Mathew, additional, Asadi, Amir, additional, and Khan, Mansoor A., additional
- Published
- 2020
- Full Text
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8. List of Contributors
- Author
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Aceves-Serrano, Lucero G., primary, Arul, K. Thanigai, additional, Bhatti, Gurjit Kaur, additional, Bhatti, Jasvinder Singh, additional, Binkhathlan, Ziyad, additional, Bozkır, Asuman, additional, Charoo, Naseem Ahmad, additional, Chircov, Cristina, additional, Das, Ishwar, additional, Dhananjayan, Venugopal, additional, Durgun, M. Ezgi, additional, Farnia, Poopak, additional, Ficai, Anton, additional, Ghanavi, Jalaledin, additional, Gherasim, Oana, additional, Grumezescu, Alexandru Mihai, additional, Grumezescu, Valentina, additional, Güngör, Sevgi, additional, Hwang, Hyundoo, additional, Jampílek, Josef, additional, Kahraman, Emine, additional, Kailasa, Suresh Kumar, additional, Karaca, Melek, additional, Kaur, Sukhjinder, additional, Khan, Mansoor A., additional, Khoee, Sepideh, additional, Koduru, Janardhan Reddy, additional, Kráľová, Katarína, additional, Küçüktürkmen, Berrin, additional, Ladchumananandasivam, Rasiah, additional, Lavasanifar, Afsaneh, additional, Manikandan, E., additional, Newton, Amaldoss M J, additional, Ordaz-Martinez, Karen A., additional, Özsoy, Yıldız, additional, Pandey, Sharad P., additional, Pandey, V.N., additional, Pandey, V.S., additional, Panjakumar, Karunamoorthy, additional, Park, Tae-Jung, additional, Rahimi, Shahnaz, additional, Rahman, Ziyaur, additional, Rao, Anita, additional, Ravichandran, Beerappa, additional, Sen, Somnath, additional, Shukla, Tripti, additional, Singh, Bhupinder, additional, Socol, Gabriel, additional, Sudheesh, M.S., additional, Tiwari, Neha, additional, Upmanyu, Neeraj, additional, Vazquez-Piñon, Matias, additional, Velayati, Ali Akbar, additional, and Vijayvergiya, Rajesh, additional
- Published
- 2019
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9. Nanoparticles for improvement in oral bioavailability
- Author
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Charoo, Naseem Ahmad, primary, Rahman, Ziyaur, additional, and Khan, Mansoor A., additional
- Published
- 2019
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10. Nanotechnology-based drug products
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Rahman, Ziyaur, primary, Charoo, Naseem A., additional, Akhter, Sohail, additional, Beg, Sarwar, additional, Reddy, Indra K., additional, and Khan, Mansoor A., additional
- Published
- 2018
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11. List of Contributors
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Adesina, Simeon K., primary, Ahmed, Osama A.A., additional, Ahmed, Tarek A., additional, Akala, Emmanuel O., additional, Akhter, Sohail, additional, Aloisio, Carolina, additional, Andaç, Müge, additional, Baydemir, Gözde, additional, Beg, Sarwar, additional, Charoo, Naseem A., additional, Denizli, Adil, additional, Dibi, Manar, additional, Dogan-Topal, Burcu, additional, El-Say, Khalid M., additional, Garnero, Claudia, additional, Georgieva, Nedyalka, additional, Handa, Hiroshi, additional, Hirvonen, Jouni, additional, Ilić, Tanja, additional, Ito, Takumi, additional, Khan, Mansoor A., additional, Klegerman, Melvin E., additional, Leyva-Gómez, Gerardo, additional, Llera-Rojas, Viridiana G., additional, Longhi, Marcela Raquel, additional, Mendoza-Muñoz, Néstor, additional, Mohammed, Alyazya, additional, Nagahara, Noriyuki, additional, Ozkan, Sibel A., additional, Pantelić, Ivana, additional, Peltonen, Leena, additional, Piñón-Segundo, Elizabeth, additional, Quintanar-Guerrero, David, additional, Rahman, Ziyaur, additional, Reddy, Indra K., additional, Saarinen, Jukka, additional, Sakamoto, Satoshi, additional, Saleh, Nadia, additional, Savić, Miroslav, additional, Savić, Sanela, additional, Savić, Snežana, additional, Shrivastava, Ambuj, additional, Suwanai, Yusuke, additional, Todosijević, Marija, additional, Tripathi, Nagesh K., additional, Tuomela, Annika, additional, Urbán-Morlán, Zaida, additional, Uslu, Bengi, additional, Yadav, Hemant K.S., additional, Yaneva, Zvezdelina, additional, Yousaf, Zubaida, additional, Zidan, Ahmed S., additional, and Zoppi, Ariana, additional
- Published
- 2018
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12. In-Situ Implant Formulation of Laurate and Myristate Prodrugs of Dolutegravir for Ultra-Long Delivery.
- Author
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Khuroo T, Mohamed EM, Dharani S, Immadi S, Nutan MTH, Lu D, Ali HI, Khan MA, and Rahman Z
- Subjects
- Heterocyclic Compounds, 3-Ring, Laurates, Myristates, Myristic Acid, Oxazines, Piperazines, Powders, Pyridones, Solubility, Prodrugs chemistry
- Abstract
The focus of present work was to synthesize prodrugs of dolutegravir (DTG) for ultra-long delivery purpose. The prodrug was synthesized by esterification of hydroxyl group with carboxyl group of fatty acid (lauric or myristic acid). The prodrugs were characterized by differential scanning calorimetry, X-ray powder diffraction, nuclear magnetic resonance, Fourier transformed infrared, near infrared-chemical imaging, pH-solubility, partition coefficient, and stability (solid and liquid). Stability studies were performed by exposing the powder drugs to 40°C/75% RH for three months and buffer solutions at room temperature for 72 h. The prodrugs and drug were formulated into in-situ implant using biodegradable polymer. Thermal, spectral, and diffractometric data indicated formation of new chemical and solid forms. Formation of prodrugs resulted in lowering of melting point of DTG from 191.1°C to 163.7 and 140.7°C for DTG-Laurate and DTG-Myristate prodrugs, respectively. A decrease in solubility of 18.2-115.9 and 124.5-1594.9 folds was observed for DTG-Laurate and DTG-Myristate, respectively compared to DTG. Similarly, the prodrugs were highly lipophilic compared to DTG. Solid-state and pH-stability profiles of DTG and prodrugs were comparable. Implant formulation released 60.1% in 77 days compared to 95.6% in 35 days in the case of DTG-Myristate and DTG, respectively. In summary, combining prodrug and drug delivery approaches can be utilized for delivering drug for ultra-long period., Competing Interests: Declaration of Interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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13. Development and Validation Of A Discriminatory Dissolution Method for Portioned Moist Snuff and Snus.
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Rahman Z, Mohamed EM, Dharani S, Khuroo T, Young M, Feng C, Cecil T, and Khan MA
- Subjects
- Nicotine, Solubility, Tobacco, Smokeless
- Abstract
Portioned moist snuff and snus, two subcategories of smokeless tobacco products (STP) were dissolution tested as a quality control test. A USP Apparatus 4 was employed to develop and validate the method. The method was assessed based on time to reach nicotine dissolution plateau, percentage difference between two profiles at each time point, relative standard deviation (RSD), and f1 (similarity) and f2 (dissimilarity) values. Based on these criteria, 200 ml volume and 8 ml/min flow were found be discriminatory. The amount of nicotine dissolved from the nine products varied widely (2.0-3.4, 2.1-4.1, 3.3-4.6, 5.5-6.6, 6.9-9.1, 11.5-14.2, 12.5-14.6, 14.0-15.5, and 15.5-19.6 mg/pouch at 60 min). RSDs of the dissolution ranges were more than 20% at earlier time points and less than 20% at later timepoints. The developed method produced distinct profiles for all the tested products, which was further confirmed by f1>15 and f2<50 values. In conclusion, the developed method was discriminatory and can be employed as a quality control test and to differentiate among moist snuff and snus products., (Copyright © 2021. Published by Elsevier Inc.)
- Published
- 2022
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14. Fractionated charge variants of biosimilars: A review of separation methods, structural and functional analysis.
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Yüce M, Sert F, Torabfam M, Parlar A, Gürel B, Çakır N, Dağlıkoca DE, Khan MA, and Çapan Y
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- Antibodies, Monoclonal, Chromatography, Liquid, Mass Spectrometry, Surface Plasmon Resonance, Biosimilar Pharmaceuticals
- Abstract
The similarity between originator and biosimilar monoclonal antibody candidates are rigorously assessed based on primary, secondary, tertiary, quaternary structures, and biological functions. Minor differences in such parameters may alter target-binding, potency, efficacy, or half-life of the molecule. The charge heterogeneity analysis is a prerequisite for all biotherapeutics. Monoclonal antibodies are prone to enzymatic or non-enzymatic structural modifications during or after the production processes, leading to the formation of fragments or aggregates, various glycoforms, oxidized, deamidated, and other degraded residues, reduced Fab region binding activity or altered FcR binding activity. Therefore, the charge variant profiles of the monoclonal antibodies must be regularly and thoroughly evaluated. Comparative structural and functional analysis of physically separated or fractioned charged variants of monoclonal antibodies has gained significant attention in the last few years. The fraction-based charge variant analysis has proved very useful for the biosimilar candidates comprising of unexpected charge isoforms. In this report, the key methods for the physical separation of monoclonal antibody charge variants, structural and functional analyses by liquid chromatography-mass spectrometry, and surface plasmon resonance techniques were reviewed., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)
- Published
- 2021
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15. Ultrasound-guided versus blind vascular access followed by REBOA on board of a medical helicopter in a hemorrhagic ovine model.
- Author
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Reva VA, Perevedentcev AV, Pochtarnik AA, Khupov MT, Kalinina AA, Samokhvalov IM, and Khan MA
- Subjects
- Animals, Aorta, France, Hemorrhage therapy, Japan, Male, Resuscitation, Sheep, Ultrasonography, Interventional, Air Ambulances, Balloon Occlusion, Endovascular Procedures, Shock, Hemorrhagic diagnostic imaging, Shock, Hemorrhagic therapy
- Abstract
Background: The aim of this study is to evaluate the feasibility of en-route resuscitative endovascular balloon occlusion of the aorta (REBOA) on board of a helicopter., Methods: Six sedated male sheep (weighing 42-54 kg) underwent a controlled hemorrhage until the systolic blood pressure (BP) dropped to <90 mmHg, and were placed into a low capacity Eurocopter AS-350 (France). During the 30-minutes normal flight, every animal underwent blind (left side) and ultrasound-guided (US) (right side) vascular access (VA) to the femoral artery followed by REBOA: the first catheter (Rescue balloon, Japan) - into Zone I, the second one (MIT, Russia) - Zone III. In case of blind VA failure, an alternate US-puncture was attempted. Six experienced flight anesthetists were enrolled into the study. Vascular access and REBOA catheter placement (confirmed by X-Ray later) success rate and timing were recorded., Results: Among six blind punctures one was successful, 2/6 - were into the vein, 3/6 - completely failed and switched to US-punctures (making total number of US-punctures nine). Eight out of nine US-punctures were successful. However, correct wire insertion and sheath placement was performed in 1/6 animal in the 'blind' group and only in 6/9 animals in the 'US' group. It took a median of 65 seconds (range 5-260) for US-puncture and a median of 4 minutes to get the sheath in. Among the 9 VAs, there were 2 REBOA failures (1 ruptured balloon [MIT] and 1 mistaken vena cava placement primarily recognized by a sudden drop of BP and later confirmed by X-Ray). Five out of seven balloons were placed in a desired intra-aortic position: 4/5 in Zone I and 1/2 - in Zone III. A median time for a successful REBOA procedure was 5.0 (range 2.5-10.0) minutes (1 min after sheath placement)., Conclusion: Our study demonstrates the potential feasibility of the en-route REBOA which can be performed within 5 minutes. Ultrasound-guidance is critically important to achieve en-route VA., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest. No specific funding was provided., (Copyright © 2020. Published by Elsevier Ltd.)
- Published
- 2021
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16. Development of Methamphetamine Abuse-Deterrent Formulations Using Sucrose Acetate Isobutyrate.
- Author
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Dharani S, Barakh Ali SF, Afrooz H, Mohamed EM, Cook P, Khan MA, and Rahman Z
- Subjects
- Delayed-Action Preparations, Sucrose analogs & derivatives, Tablets, Abuse-Deterrent Formulations, Methamphetamine
- Abstract
The objective of the present research was to investigate application of sucrose acetate isobutyrate (SAIB) in the development of a meth-deterrent formulation in combination with polyethylene oxide (Polyox
TM ) and hydroxypropyl methylcellulose. The formulations were prepared by granulating pseudoephedrine hydrochloride, hydroxypropyl methylcellulose, and PolyoxTM with an ethanolic solution of SAIB and compressed into tablets followed by heat curing. The tablets were characterized for surface morphology, crystallinity, drug distribution, hardness, particle size, extraction, and dissolution. Hardness increased insignificantly, surface morphology indicated cracking and crevices, and diffractograms showed an increase and a decrease in drug and PolyoxTM crystallinity, respectively, after heat curing. Pseudoephedrine hydrochloride, PolyoxTM , and SAIB distribution was uniform as indicated by near infrared image. The drug extraction varied from 69.5% to 77.8%, 90.3% to 106.5%, 51.3% to 81.2%, and 48.9% to 72.6% in water, ethanol, 0.1 N HCl, and 0.1 N NaOH, respectively. The dissolution was more than 85% in 9 h from all the formulations. Thus, the addition of SAIB to the formulation decreased the drug extraction in various solvents which has the potential to decrease abuse of pseudoephedrine formulation for methamphetamine synthesis., (Copyright © 2020 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)- Published
- 2020
- Full Text
- View/download PDF
17. Univariate and Multivariate Models for Determination of Prasugrel Base in the Formulation of Prasugrel Hydrochloride Using XRPD Method.
- Author
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Dharani S, Barakh Ali SF, Afrooz H, Khan MA, and Rahman Z
- Subjects
- Chemistry, Pharmaceutical methods, Excipients chemistry, Powder Diffraction methods, Powders chemistry, Tablets chemistry, X-Ray Diffraction methods, Prasugrel Hydrochloride chemistry
- Abstract
Prasugrel hydrochloride (PHCl) undergoes salt disproportionation, and the resulting prasugrel free base (PFB) may lead to the poor in vitro and or in vivo performance of the drug product. The aim of the present work was to develop univariate and multivariate models based on X-ray powder diffraction to quantify the salt and base in the powder and tablet formulations. Compositionally identical formulations of PHCl and PFB were prepared and mixed in various proportions to make 0%-30% PFB sample matrices. The formulations consisted of commonly used excipients, which are generally used in commercially available products. X-ray powder diffraction data were collected and subjected to the least square regression and partial least square regression analysis. The model performance parameters such as root mean squared and standard errors were low for univariate models compared to partial least square regression multivariate models. Model predicted values of the independent sample matrices by both methods matched closely with the actual values of PFB and PHCl. However, residual and standard deviation were low in univariate models predicted values. The models developed in this work have been shown to quantitate the PHCl disproportionation to PFB fraction in the drug product and provide a means to control the disproportionation of PHCl., (Copyright © 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
18. Development and Validation of a Discriminatory Dissolution Method for Rifaximin Products.
- Author
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Dharani S, Barakh Ali SF, Afrooz H, Khan MA, and Rahman Z
- Subjects
- Buffers, Drug Stability, Sodium Dodecyl Sulfate chemistry, Solubility, Solvents chemistry, Tablets, Water chemistry, Anti-Bacterial Agents chemistry, Chemistry, Pharmaceutical methods, Drug Compounding standards, Quality Control, Rifaximin chemistry
- Abstract
The commercial product of rifaximin (RFX) contains α form. The α form can change to β form on exposure to high humidity that can occur during manufacturing, stability, and in-use period. It is critical to maintain α form of the drug in a drug product to avoid variability in clinical response. U.S. Food and Drug Administration dissolution method was found to be nondiscriminatory for RFX formulations containing either 100% α or β form. The objective of this study was to develop a discriminatory dissolution method that can detect low levels of α to β transformation in RFX products. Formulations containing a variable fraction of α and β forms were prepared by using direct compression method. Dissolution parameters investigated were type of dissolution medium (water and phosphate buffer), volume (500, 900, and 1000 mL), and paddle speed (50, 75, and 150 rpm). Dissolution in water with 0.2% sodium lauryl sulfate was less than 80% and nondiscriminatory. However, dissolution tested in a phosphate buffer pH 7.4 with 0.2% sodium lauryl sulfate at 50 rpm was discriminatory with more than 17.5% difference in dissolution profile between formulations containing α and β forms. The developed method can detect polymorphic transformation if there is 25% or more β form conversion., (Copyright © 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
19. Quality and In-Use Stability Comparison of Brand and Generics of Extended-Release Phenytoin Sodium Capsules.
- Author
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Dharani S, Barakh Ali SF, Afrooz H, Bhattacharya R, Khan MA, and Rahman Z
- Subjects
- Excipients chemistry, Hydrogen-Ion Concentration, Lactose chemistry, Solubility drug effects, Capsules chemistry, Drugs, Generic chemistry, Phenytoin chemistry
- Abstract
The objective of the present study was to understand quality of brand and generic products of phenytoin sodium by in vitro methods. Three commercial products were selected for the study, 1 brand and 2 generics (product-A, product-B, and product-C). Products were repacked in pharmacy vials and stored for 12 weeks at 30°C/75% RH to simulate in-use conditions. The products were examined visually and microscopically for morphologic changes, spectroscopic and diffractometric methods for chemical changes, and dissolution, assay, and impurities for performance evaluation. Capsules content of the product-A turned yellowish to dark orange color from initial white powder, which indicated a possible chemical interaction between lactose and the drug in addition to disproportionation. This was supported by pH, microscopic, spectroscopic, and X-ray diffraction data. Product-A failed to meet United States Pharmacopoeia dissolution specification of 75% in 120 min after 2-weeks whereas product-B and product-C failed at 6-weeks of in-use stability conditions exposure. Furthermore, product-A also failed to meet United States pharmacopoeia assay and impurities specifications in 12 weeks in-use period. In summary, this study indicated salt disproportionation, chemical interactions, and phase transformations of drug and excipients in the commercial products of phenytoin sodium, which may affect the clinical performance of the product., (Copyright © 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
- Full Text
- View/download PDF
20. Chemometric Models for Quantification of Carbamazepine Anhydrous and Dihydrate Forms in the Formulation.
- Author
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Barakh Ali SF, Rahman Z, Dharani S, Afrooz H, and Khan MA
- Subjects
- Biological Availability, Carbamazepine chemistry, Carbamazepine pharmacokinetics, Crystallization, Drug Liberation, Least-Squares Analysis, Principal Component Analysis, Solubility, Spectroscopy, Fourier Transform Infrared, Tablets, Carbamazepine analysis, Chemistry, Pharmaceutical methods, Excipients chemistry, Models, Chemical
- Abstract
Carbamazepine (CBZ) exists in anhydrous and dihydrate forms. These forms differ in their solubility, dissolution rate, and subsequently in their oral bioavailability. The objective of this study is to develop multivariate chemometric models for estimation of the low level of carbamazepine dihydrate (CBZ-DH) in the CBZ formulations containing excipients of the commercial formulation. The selected excipients were mixed in proportions to make sample matrices ranging from 0% to 50% CBZ-DH. Fourier transform infrared (FTIR), near infrared (NIR), and hyperspectral imaging data were mathematically pretreated before the development of partial least square and principal component analysis regression models. The developed partial least squares regression and principal component analysis models demonstrated predictability of CBZ and CBZ-DH by multiple scattering correction and standard normal variate processing methods. Among the spectroscopic techniques used the model performance parameters such as root-mean-square error, standard error, and bias were found to be low for NIR compared to FTIR. The treated data have shown better model fitting than without treatment, which was demonstrated by correlation coefficient of 0.9778, 0.9824, and 0.9852 for FTIR, NIR, and hyperspectral imaging, respectively. Furthermore, the predicted values were found to be very close to the selected low level of independent samples having 5% CBZ-DH in tablet formulation., (Copyright © 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
- Full Text
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21. A meta-analysis of the efficacy of whole-body computed tomography imaging in the management of trauma and injury.
- Author
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Chidambaram S, Goh EL, and Khan MA
- Subjects
- Humans, Injury Severity Score, Multiple Trauma mortality, Survival Rate, Emergency Service, Hospital, Multiple Trauma diagnostic imaging, Tomography, X-Ray Computed, Whole Body Imaging
- Abstract
Background: Traumatic injury is the third leading cause of death overall. To optimize the outcomes in these patients, hospitals employ whole-body computed tomography (WBCT) imaging due to the high diagnostic yield and potential to identify missed injuries. However, this delays time-critical interventions. Currently, there is an absence of any high-level evidence to support or refute either view. We present a meta-analysis of the available literature to elucidate the efficacy of WBCT in improving the outcomes of trauma, specifically the mortality rate., Methods: A systematic review of studies comparing WBCT and selective CT imaging in secondary survey was conducted, using MEDLINE, EMBASE, the Cochrane Review and Scopus databases. The articles were evaluated for intervention using WBCT to reduce mortality rate, followed by subgroup analysis for other secondary measures, using Review Manager 5.3 software., Results: Eleven studies of 32,207 patients were included. There were lower overall (OR=0.79; 95% CI 0.74,0.83, p<0.05) and 24h mortality rates (OR=0.72, 95% CI 0.66,0.79, p<0.05) in the WBCT cohort. Additionally, patients in the WBCT arm spent less time in the emergency room (MD=-14.81; 95% CI -17.02, -12.60, p<0.00001) and needing ventilation (MD=-2.01; 95% CI -2.41, -1.62, p<0.05) despite a higher baseline injury severity score., Conclusion: The analysis shows that WBCT is associated with better outcomes, including a lower overall and 24h mortality rate, however the included studies are mostly observational and show considerable heterogeneity. Further work is required to make definitive clinical recommendations for a tailored algorithm in managing trauma patients., (Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2017
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22. Evaluation of the In Vitro Efficacy of Sevelamer Hydrochloride and Sevelamer Carbonate.
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Yang Y, Mohammad A, Berendt RT, Carlin A, Khan MA, and Faustino PJ
- Subjects
- Drug Evaluation, Preclinical methods, Drug Evaluation, Preclinical standards, Chelating Agents chemistry, Chelating Agents metabolism, Pharmacopoeias as Topic standards, Sevelamer chemistry, Sevelamer metabolism
- Abstract
The objective of this project is to develop an in vitro approach that can be used to determine the phosphate binding capacity of sevelamer hydrochloride and carbonate for both drug products and active pharmaceutical ingredients (APIs). A simple and efficient inductively coupled plasma spectrometer method for analysis of phosphate at physiologically relevant pH conditions has been developed and validated. The method addresses each of the analytical validation characteristics such as linearity, accuracy, precision, stability, and selectivity, and meets the acceptance criteria defined in the United States Food and Drug Administration guidance (Food and Drug Administration, Center for Drug Evaluation and Research. 2001. Guidance for industry-Bioanalytical method validation, May). The in vitro phosphate binding efficacies were systematically evaluated and compared for two drug products and two APIs. The phosphate binding profiles appeared similar between the drug products. Under all conditions, the sevelamer-phosphate binding reached equilibrium at 6 h. The 90% confidence interval for the k2 ratio (sevelamer carbonate vs. sevelamer hydrochloride) was well within 80%-125% under all pH conditions. However, the k1 ratio varied, indicating that there exists difference in the binding affinity. Our findings will be useful in assisting with "in vivo" biowaiver for the approval of generic sevelamer drug products., (Published by Elsevier Inc.)
- Published
- 2016
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23. Managing a Rare Malignant Sweat Gland Tumor Invading the Brain: Case Report and Literature Review.
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Jagannatha AT, Khan MA, Karanth S, Srikantha U, Varma R, and Mahadevan A
- Subjects
- Acrospiroma diagnostic imaging, Aged, Humans, Male, Neoplasm Invasiveness, Radiography, Sweat Gland Neoplasms diagnostic imaging, Acrospiroma pathology, Acrospiroma surgery, Scalp, Sweat Gland Neoplasms pathology, Sweat Gland Neoplasms surgery
- Abstract
Background: Malignant sweat gland adnexal tumors are rare with an incidence of 0.001%. Of these, clear cell hidradenocarcinoma is an extremely uncommon subtype that accounts for 6% of malignant eccrine sweat gland tumors. They occur commonly in the head, neck, and extremities. Although they have a propensity for local recurrence, intracranial extension with brain invasion is extremely rare., Case Description: We report a 76-year-old man with a large, recurring, ulcerated, fungating scalp swelling of 14 years who presented with focal seizures and drowsiness. Neuroimaging revealed a massive tumor arising from the scalp to invade the left parietal lobe and extending to the right side with occlusion of the superior sagittal sinus. The overlying parietal bone was lytic with a "moth-eaten" appearance. He underwent wide excision of the scalp lesion, near-total cerebral tumor decompression followed by titanium mesh cranioplasty, rotation flap reconstruction of the scalp, and adjuvant radiotherapy to the skull vault. Histopathology revealed clear cell hidradenocarcinoma. Whole-body positron emission tomography scan did not reveal any other lesion. At 24 months' follow-up, he remains recurrence free., Conclusion: We report a rare indolent case of clear cell hidradenocarcinoma invading the brain, which was managed with near-total decompression and adjuvant radiotherapy. Intracranial extension in such aggressive tumors poses challenges in management, and regular neuroimaging surveillance is advised., (Copyright © 2016 Elsevier Inc. All rights reserved.)
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- 2016
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24. Spectroscopic-Based Chemometric Models for Quantifying Low Levels of Solid-State Transitions in Extended Release Theophylline Formulations.
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Korang-Yeboah M, Rahman Z, Shah DA, and Khan MA
- Subjects
- Crystallization, Delayed-Action Preparations, Drug Stability, Phase Transition, Spectroscopy, Near-Infrared, Spectrum Analysis, Raman, Bronchodilator Agents administration & dosage, Bronchodilator Agents chemistry, Models, Chemical, Theophylline administration & dosage, Theophylline chemistry
- Abstract
Variations in the solid state form of a pharmaceutical solid have profound impact on the product quality and clinical performance. Quantitative models that allow rapid and accurate determination of polymorphic changes in pharmaceutical products are essential in ensuring product quality throughout its lifecycle. This study reports the development and validation of chemometric models of Raman and near infrared spectroscopy (NIR) for quantifying the extent of pseudopolymorphic transitions of theophylline in extended release formulations. The chemometric models were developed using sample matrices consisting of the commonly used excipients and at the ratios in commercially available products. A combination of scatter removal (multiplicative signal correction and standard normal variate) and derivatization (Savitzky-Golay second derivative) algorithm were used for data pretreatment. Partial least squares and principal component regression models were developed and their performance assessed. Diagnostic statistics such as the root mean square error, correlation coefficient, bias and Q(2) were used as parameters to test the model fit and performance. The models developed had a good fit and performance as shown by the values of the diagnostic statistics. The model diagnostic statistics were similar for MSC-SG and SNV-SG treated spectra. Similarly, PLSR and PCR models had comparable performance. Raman chemometric models were slightly better than their corresponding NIR model. The Raman and NIR chemometric models developed had good accuracy and precision as demonstrated by closeness of the predicted values for the independent observations to the actual TMO content hence the developed models can serve as useful tools in quantifying and controlling solid state transitions in extended release theophylline products., (Copyright © 2016. Published by Elsevier Inc.)
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- 2016
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25. Evaluation of In-Use Stability of Anticoagulant Drug Products: Warfarin Sodium.
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Nguyenpho A, Ciavarella AB, Siddiqui A, Rahman Z, Akhtar S, Hunt R, Korang-Yeboah M, and Khan MA
- Subjects
- Calorimetry, Differential Scanning methods, Chemistry, Pharmaceutical methods, Crystallization methods, Drug Stability, Hardness, Humidity, Powders chemistry, Solubility, Tablets chemistry, Temperature, X-Ray Diffraction methods, Anticoagulants chemistry, Warfarin chemistry
- Abstract
The objective of the study was to evaluate the stability of warfarin products during use by patients or caregivers. For evaluation, three commercial products manufactured by different processes were selected and placed at 30°C/75%RH to simulate in use condition. Samples were withdrawn up to 12 weeks and analyzed for the physicochemical changes. Scanning electron microscopy demonstrated increasing holes and craters in the tablets over the timeframe. Near-infrared chemical imaging and powder X-ray powder diffraction corroborated the change arising from conversion of crystalline to amorphous forms of the drug. Hardness and disintegration time of the tablets were found to increase progressively. With increasing time, moisture contents of the products were found to increase and consequent decrease in isopropyl alcohol content of the product. Dissolution of the tablets in media at pH 4.5 demonstrated discrimination between crystalline and amorphous drug products. Overall, percent drug dissolved in each product at 30 min was found to decrease with increasing exposure time. Dissolution of drug decreased from 54% to 38% and 82% to 54% for the two products while the third product maintained consistently high level of dissolution. These results suggest that the drug product quality attributes can change during use., (© 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.)
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- 2015
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26. Chemometric Model Development and Comparison of Raman and (13)C Solid-State Nuclear Magnetic Resonance-Chemometric Methods for Quantification of Crystalline/Amorphous Warfarin Sodium Fraction in the Formulations.
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Rahman Z, Mohammad A, Akhtar S, Siddiqui A, Korang-Yeboah M, and Khan MA
- Subjects
- Calibration, Chemical Phenomena, Drug Compounding, Informatics, Least-Squares Analysis, Magnetic Resonance Spectroscopy, Powders, Principal Component Analysis, Quality Control, Reproducibility of Results, Spectroscopy, Near-Infrared, Spectrum Analysis, Raman, Anticoagulants chemistry, Models, Chemical, Warfarin chemistry
- Abstract
Warfarin sodium (WS) exists in multiple solid-state forms. The solid-state forms differ in physicochemical properties, and crystalline changes in the drug formulation may influence on the drug product quality and/or clinical performance. It is, therefore, critically important to have a good and reliable analytical method to monitor and quantitate this transformation during stability studies. The aim of the present research was to investigate Raman spectroscopy and solid-state nuclear magnetic resonance ((13)C ssNMR) methods in conjunction with chemometry to quantitate the amorphous and crystalline WS fractions in the drug products. Compositionally identical formulations of amorphous and crystalline WS were prepared, and mixed in various proportions to make 0%-100% amorphous/crystalline sample matrices. Raman and (13)C ssNMR spectra were collected and subjected to partial-least-squares and principle component regressions after mathematical treatment of the data. The model performance parameters such as root-mean-square error of prediction, standard error of prediction, and bias were low for Raman models in comparison to (13)C ssNMR models. Models predicted values of the independent sample matrices match closely with the actual values at high level of crystalline WS. Thus, the developed methods provide means to control and quantitate the WS forms fraction in the drug product., (Published 2015. This article is a U.S. Government work and is in the public domain in the USA.)
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- 2015
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27. Comparison of X-ray powder diffraction and solid-state nuclear magnetic resonance in estimating crystalline fraction of tacrolimus in sustained-release amorphous solid dispersion and development of discriminating dissolution method.
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Rahman Z, Bykadi S, Siddiqui A, and Khan MA
- Subjects
- Crystallization, Delayed-Action Preparations, Solubility, Magnetic Resonance Spectroscopy methods, Powder Diffraction methods, Tacrolimus analysis, Tacrolimus chemistry, X-Ray Diffraction methods
- Abstract
The focus of present investigation was to explore X-ray powder diffraction (XRPD) and solid-state nuclear magnetic resonance (ssNMR) techniques for amorphous and crystalline tacrolimus quantification in the sustained-release amorphous solid dispersion (ASD), and to propose discriminating dissolution method that can detect crystalline drug. The ASD and crystalline physical mixture was mixed in various proportions to make sample matrices containing 0%-100% crystalline-amorphous tacrolimus. Partial-least-square regression and principle component regression were applied to the spectral data. Dissolution of the ASD in the US FDA recommended dissolution medium with and without surfactant was performed. R(2) > 0.99 and slope was close to one for all the models. Root-mean-square of prediction, standard error of prediction, and bias were higher in ssNMR-based models when compared with XRPD data models. Dissolution of the ASD decreased with an increase in the crystalline tacrolimus in the formulations. Furthermore, detection of crystalline tacrolimus in the ASD was progressively masked with an increase in the surfactant level in the dissolution medium. XRPD and ssNMR can be used equally to quantitate the crystalline and amorphous fraction of tacrolimus in the ASD with good accuracy; however, ssNMR data collection time is excessively long, and minimum surfactant level in the dissolution medium maximizes detection of crystalline reversion in the formulation., (Published 2015. This article is a U.S. Government work and is in the public domain in the USA.)
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- 2015
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28. Chemometric methods for the quantification of crystalline tacrolimus in solid dispersion by powder X-ray diffractrometry.
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Siddiqui A, Rahman Z, Bykadi S, and Khan MA
- Subjects
- Chemistry, Pharmaceutical methods, Crystallization methods, Excipients chemistry, Least-Squares Analysis, Powder Diffraction methods, Principal Component Analysis, Spectroscopy, Near-Infrared methods, X-Ray Diffraction methods, Powders chemistry, Tacrolimus chemistry
- Abstract
The objective of this study was to develop powder X-ray diffraction (XRPD) chemometric model for quantifying crystalline tacrolimus from solid dispersion (SD). Three SDs (amorphous tacrolimus component) with varying drug to excipient ratios (24.4%, 6.7%, and 4.3% drug) were prepared. Placebo SDs were mixed with crystalline tacrolimus to make their composition equivalent to three SD (crystalline tacrolimus component). These two components were mixed to cover 0%-100% of crystalline drug. Uniformity of the sample mixtures was confirmed by near-infrared chemical imaging. XRPD showed three distinct peaks of crystalline drug at 8.5°, 10.3°, and 11.2° (2θ), which were nonoverlapping with the excipients. Principal component regressions (PCR) and partial least square (PLS) regression used in model development showed high R(2) (>0.99) for all the mixtures. Overall, the model showed low root mean square of standard error, standard error, and bias, which was smaller in PLS than PCR-based model. Furthermore, the model performance was evaluated on the formulations with known percentage of crystalline drug. Model-calculated crystalline drug percentage values were close to actual value. Therefore, these studies strongly suggest the application of chemometric-XRPD models as a quality control tool to quantitatively predict the crystalline drug in the formulation., (© 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.)
- Published
- 2014
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29. Near-infrared and fourier transform infrared chemometric methods for the quantification of crystalline tacrolimus from sustained-release amorphous solid dispersion.
- Author
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Rahman Z, Siddiqui A, Bykadi S, and Khan MA
- Subjects
- Crystallization, Immunosuppressive Agents administration & dosage, Least-Squares Analysis, Principal Component Analysis, Spectroscopy, Fourier Transform Infrared methods, Spectroscopy, Near-Infrared methods, Tacrolimus administration & dosage, Delayed-Action Preparations chemistry, Immunosuppressive Agents chemistry, Tacrolimus chemistry
- Abstract
The objective of the present research was to study the feasibility of using near-infrared (NIR) and Fourier transform infrared (FTIR)-based chemometric models in quantifying crystalline and amorphous tacrolimus from its sustained-release amorphous solid dispersion (ASD). ASD contained ethyl cellulose, hydroxypropyl methyl cellulose, and lactose monohydrate as carriers, and amorphous form of tacrolimus in it was confirmed by X-ray powder diffraction. Crystalline physical mixture was mixed with ASD in various proportions to prepare sample matrices containing 0%-100% amorphous/crystalline tacrolimus. NIR and FTIR of the samples were recorded, and data were mathematically pretreated using multiple scattering correction, standard normal variate, or Savitzky-Golay before multivariate analysis, partial-least-square regression (PLSR), and principle component regression (PCR). The PLSR models were more accurate than PCR for NIR and FTIR data as indicated by low value of root-mean-squared error of prediction, standard error of prediction and bias, and high value of R(2). Additionally, NIR data-based models were more accurate and precise than FTIR data models. In conclusion, NIR chemometric models provide simple and fast method to quantitate crystalline tacrolimus in the ASD formulation., (© 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.)
- Published
- 2014
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30. An integrated process analytical technology (PAT) approach to monitoring the effect of supercooling on lyophilization product and process parameters of model monoclonal antibody formulations.
- Author
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Awotwe Otoo D, Agarabi C, and Khan MA
- Subjects
- Calorimetry, Differential Scanning, Chemistry, Pharmaceutical, Crystallization, Drug Compounding, Drug Stability, Surface Properties, Transition Temperature, Antibodies, Monoclonal chemistry, Freeze Drying, Immunoglobulin G chemistry, Models, Chemical, Technology, Pharmaceutical methods
- Abstract
The aim of the present study was to apply an integrated process analytical technology (PAT) approach to control and monitor the effect of the degree of supercooling on critical process and product parameters of a lyophilization cycle. Two concentrations of a mAb formulation were used as models for lyophilization. ControLyo™ technology was applied to control the onset of ice nucleation, whereas tunable diode laser absorption spectroscopy (TDLAS) was utilized as a noninvasive tool for the inline monitoring of the water vapor concentration and vapor flow velocity in the spool during primary drying. The instantaneous measurements were then used to determine the effect of the degree of supercooling on critical process and product parameters. Controlled nucleation resulted in uniform nucleation at lower degrees of supercooling for both formulations, higher sublimation rates, lower mass transfer resistance, lower product temperatures at the sublimation interface, and shorter primary drying times compared with the conventional shelf-ramped freezing. Controlled nucleation also resulted in lyophilized cakes with more elegant and porous structure with no visible collapse or shrinkage, lower specific surface area, and shorter reconstitution times compared with the uncontrolled nucleation. Uncontrolled nucleation however resulted in lyophilized cakes with relatively lower residual moisture contents compared with controlled nucleation. TDLAS proved to be an efficient tool to determine the endpoint of primary drying. There was good agreement between data obtained from TDLAS-based measurements and SMART™ technology. ControLyo™ technology and TDLAS showed great potential as PAT tools to achieve enhanced process monitoring and control during lyophilization cycles., (© 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.)
- Published
- 2014
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31. Stereomicroscopic imaging technique for the quantification of cold flow in drug-in-adhesive type of transdermal drug delivery systems.
- Author
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Krishnaiah YS, Katragadda U, and Khan MA
- Subjects
- Administration, Cutaneous, Cold Temperature, Skin drug effects, Adhesives chemistry, Drug Delivery Systems methods, Microscopy methods
- Abstract
Cold flow is a phenomenon occurring in drug-in-adhesive type of transdermal drug delivery systems (DIA-TDDS) because of the migration of DIA coat beyond the edge. Excessive cold flow can affect their therapeutic effectiveness, make removal of DIA-TDDS difficult from the pouch, and potentially decrease available dose if any drug remains adhered to pouch. There are no compendial or noncompendial methods available for quantification of this critical quality attribute. The objective was to develop a method for quantification of cold flow using stereomicroscopic imaging technique. Cold flow was induced by applying 1 kg force on punched-out samples of marketed estradiol DIA-TDDS (model product) stored at 25°C, 32°C, and 40°C/60% relative humidity (RH) for 1, 2, or 3 days. At the end of testing period, dimensional change in the area of DIA-TDDS samples was measured using image analysis software, and expressed as percent of cold flow. The percent of cold flow significantly decreased (p < 0.001) with increase in size of punched-out DIA-TDDS samples and increased (p < 0.001) with increase in cold flow induction temperature and time. This first ever report suggests that dimensional change in the area of punched-out samples stored at 32°C/60%RH for 2 days applied with 1 kg force could be used for quantification of cold flow in DIA-TDDS., (© 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.)
- Published
- 2014
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32. Analytical methods for the evaluation of melamine contamination.
- Author
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Cantor SL, Gupta A, and Khan MA
- Subjects
- Calorimetry, Differential Scanning, Drug Contamination, Gelatin analysis, Principal Component Analysis, Spectroscopy, Fourier Transform Infrared, Spectroscopy, Near-Infrared, Spectrum Analysis, Raman, Thermogravimetry, X-Ray Diffraction, Triazines analysis
- Abstract
There is an urgent need for the analysis of melamine in the global pharmaceutical supply chain to detect economically motivated adulteration or unintentional contamination using a simple, nondestructive analytical technique that confirms the extent of adulteration in a shorter time period. In this work, different analytical techniques (thermal analysis, X-ray diffraction, Fourier transform infrared (FT-IR), FT-Raman, and near-infrared (NIR) spectroscopy) were evaluated for their ability to detect a range of melamine levels in gelatin. While FT-IR and FT-Raman provided qualitative assessment of melamine contamination or adulteration, powder X-ray diffraction and NIR were able to detect and quantify the presence of melamine at levels as low as 1.0% w/w. Multivariate analysis of the NIR data yielded the most accurate model when three principal components were used. Data were pretreated using standard normal variate transformation to remove multiplicative interferences of scatter and particle size. The model had a root-mean-square error of calibration of 2.4 (R(2) = 0.99) and root-mean square error of prediction of 2.5 (R(2) = 0.96). The value of the paired t test for actual and predicted samples (1%-50% w/w) was 0.448 (p < 0.05), further indicating the robustness of the model., (Published 2013. This article is a U.S. Government work and is in the public domain in the USA.)
- Published
- 2014
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33. Characterization of a nonribosomal peptide antibiotic solid dispersion formulation by process analytical technologies sensors.
- Author
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Rahman Z, Siddiqui A, and Khan MA
- Subjects
- Crystallization, Excipients chemistry, Least-Squares Analysis, Polyethylene Glycols chemistry, Powder Diffraction, Principal Component Analysis, Solubility, Spectroscopy, Fourier Transform Infrared, X-Ray Diffraction, Anti-Bacterial Agents chemistry, Vancomycin chemistry
- Abstract
The focus of present investigation was to characterize and evaluate the variability of solid dispersion (SD) of amorphous vancomycin (VCM), utilizing crystalline polyethylene glycol (PEG-6000) as a carrier and subsequently, determining their percentage composition by nondestructive method of process analytical technology (PAT) sensors. The SD were prepared by heat fusion method and characterized for physicochemical and spectral properties. Enhanced dissolution was shown by the SD formulations. Decreased crystallinity of PEG-6000 was observed indicating that the drug was present as solution and dispersed form within the polymer. The SD formulations were homogenous as shown by near infrared (NIR) chemical imaging data. Principal component analysis (PCA) and partial least square (PLS) method were applied to NIR and PXRD (powder X-ray diffraction) data to develop model for quantification of drug and carrier. PLS of both data showed correlation coefficient >0.9934 with good prediction capability as revealed by smaller value of root mean square and standard error. The model based on NIR and PXRD were two folds more accurate in estimating PEG-6000 than VCM. In conclusion, the drug dissolution from the SD increased by decreasing crystallinity of PEG-6000, and the chemometric models showed usefulness of PAT sensor in estimating percentage of both VCM and PEG-600 simultaneously., (© 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.)
- Published
- 2013
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34. Chemometric evaluation of near infrared, fourier transform infrared, and Raman spectroscopic models for the prediction of nimodipine polymorphs.
- Author
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Siddiqui A, Rahman Z, Sayeed VA, and Khan MA
- Subjects
- Crystallization, Least-Squares Analysis, Models, Chemical, Spectroscopy, Fourier Transform Infrared methods, Spectroscopy, Near-Infrared methods, Spectrum Analysis, Raman methods, Antihypertensive Agents chemistry, Nimodipine chemistry
- Abstract
The objective of this study was to assess the performance of the chemometric model to predict the proportion of the recrystallized polymorphs of nimodipine from the cosolvent formulations. Ranging from 100% to 0% (w/w) of polymorph I, the two polymorphs mixtures were prepared and characterized spectroscopically using Fourier transformed infrared spectroscopy (FTIR), near-infrared spectroscopy (NIR), and Raman spectroscopy. Instrumental responses were treated to construct multivariate calibration model using principal component regression (PCR) and partial least square regression approaches. Treated data showed better model fitting than without treatment, which demonstrated higher correlation coefficient (R(2) ) and lower root mean square of standard error (RMSE) and standard error (SE). Multiple scattering correction and standard normal variate exhibited higher R(2) and lower RMSE and SE values than second derivative. Goodness of fit for FTIR and NIR (R(2) ∼ 0.99) data was better than Raman (R(2) ∼ 0.95). Furthermore, the models were applied on the recrystallized polymorphs obtained by storing nimodipine-cosolvent formulations at selected stability conditions. The relative composition of the polymorphs differed with storage conditions. NIR-chemical imaging on recrystallized sample of nimodipine at 15°C qualitatively corroborated the model-based prediction of the two polymorphs. Therefore, these studies strongly suggest the importance of the potential utility of the chemometric model in predicting nimodipine polymorphs., (© 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.)
- Published
- 2013
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35. Development and evaluation of paclitaxel nanoparticles using a quality-by-design approach.
- Author
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Yerlikaya F, Ozgen A, Vural I, Guven O, Karaagaoglu E, Khan MA, and Capan Y
- Subjects
- Antineoplastic Agents chemistry, Chemistry, Pharmaceutical methods, Drug Delivery Systems methods, Particle Size, Nanoparticles chemistry, Paclitaxel chemistry
- Abstract
The aims of this study were to develop and characterize paclitaxel nanoparticles, to identify and control critical sources of variability in the process, and to understand the impact of formulation and process parameters on the critical quality attributes (CQAs) using a quality-by-design (QbD) approach. For this, a risk assessment study was performed with various formulation and process parameters to determine their impact on CQAs of nanoparticles, which were determined to be average particle size, zeta potential, and encapsulation efficiency. Potential risk factors were identified using an Ishikawa diagram and screened by Plackett-Burman design and finally nanoparticles were optimized using Box-Behnken design. The optimized formulation was further characterized by Fourier transform infrared spectroscopy, X-ray diffractometry, differential scanning calorimetry, scanning electron microscopy, atomic force microscopy, and gas chromatography. It was observed that paclitaxel transformed from crystalline state to amorphous state while totally encapsulating into the nanoparticles. The nanoparticles were spherical, smooth, and homogenous with no dichloromethane residue. In vitro cytotoxicity test showed that the developed nanoparticles are more efficient than free paclitaxel in terms of antitumor activity (more than 25%). In conclusion, this study demonstrated that understanding formulation and process parameters with the philosophy of QbD is useful for the optimization of complex drug delivery systems., (© 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.)
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- 2013
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36. Oseltamivir phosphate-amberlite(TM) IRP 64 ionic complex for taste masking: preparation and chemometric evaluation.
- Author
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Siddiqui A, Shah RB, and Khan MA
- Subjects
- Antiviral Agents chemistry, Child, Humans, Hydrogen-Ion Concentration, Ions chemistry, Oseltamivir chemistry, Spectroscopy, Fourier Transform Infrared, Spectroscopy, Near-Infrared, Tongue physiology, Antiviral Agents administration & dosage, Drug Carriers chemistry, Oseltamivir administration & dosage, Resins, Synthetic chemistry, Taste
- Abstract
The objective of the present work was to evaluate and characterize a pediatric-friendly formulation of a bitter tasting drug, oseltamivir phosphate (drug). Amberlite IRP64 (resin) was used to make ionic complexes for masking its bitterness. Complexes of four drug-to-resin ratios, 1:1, 1:2, 1:4, and 1:6 (w/w), were prepared and characterized. At buccal pH of 6.8, drug-resin complexes of 1:1, 1:2, 1:4, and 1:6 ratios released 42.13%, 23.26%, 4.13%, and 14.94%, respectively, of loaded drug after 20 s. However, at stomach pH of 1.2 (0.1 N HCl), 61.96%, 70.18%, 85.88%, and 91.42% of drug was released from the same complexes in 6 min. Near-infrared (NIR) chemical imaging of the complexes showed homogeneous distribution of drug in the resin. Chemometric partial least squares model using NIR data of the drug showed a high correlation between calibration and predicted data (R(2) > 0.998). Overall, these results indicated the complex formation between drug and resin. The pH dependence of drug release from these complexes could minimize drug release in the mouth, whereas immediately releasing it in the stomach. Electronic tongue used to evaluate taste indicated that conductivity taste signals were different from control, suggesting taste masking of the drug., (Copyright © 2013 Wiley Periodicals, Inc.)
- Published
- 2013
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37. Process analytical technology to understand the disintegration behavior of alendronate sodium tablets.
- Author
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Xu X, Gupta A, Sayeed VA, and Khan MA
- Subjects
- Equipment Design, Hydrogen-Ion Concentration, Particle Size, Solubility, Tablets, Alendronate chemistry, Bone Density Conservation Agents chemistry, Chemistry, Pharmaceutical instrumentation
- Abstract
Various adverse events including esophagus irritations have been reported with the use of alendronate tablets, likely attributed to the rapid tablet disintegration in the mouth or esophagus. Accordingly, the disintegration of six alendronate tablet drug products was studied using a newly developed testing device equipped with in-line sensors, in addition to the official compendial procedure for measuring the disintegration time. The in-line sensors were used to monitor the particle count and solution pH change to assess the onset and duration of disintegration. A relatively large variation was observed in the disintegration time of the tested drug products using the compendial method. The data collected using the in-line sensors suggested that all tested drug products exhibited almost instantaneous onset of disintegration, under 2 s, and a sharp drop in solution pH. The drop in pH was slower for tablets with slower disintegration. The in-house prepared alendronate test tablets also showed similar trends suggesting rapid solubilization of the drug contributed to the fast tablet disintegration. This research highlights the usefulness of the newly developed in-line analytical method in combination with the compendial method in providing a better understanding of the disintegration and the accompanying drug solubilization processes for fast disintegrating tablet drug products., (Copyright © 2013 Wiley Periodicals, Inc.)
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- 2013
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38. Comparative evaluation of the in vitro efficacy of lanthanum carbonate chewable tablets.
- Author
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Yang Y, Bykadi S, Carlin AS, Shah RB, Yu LX, and Khan MA
- Subjects
- Humans, Hydrogen-Ion Concentration, Kidney Failure, Chronic drug therapy, Kinetics, Lanthanum chemistry, Tablets, Lanthanum pharmacology, Phosphates metabolism
- Abstract
The aims of this study were to systematically evaluate the effects of pH levels, phosphate concentrations, and tablet integrity on the phosphate binding profiles of lanthanum carbonate chewable tablets, and to compare the in vitro phosphate binding efficacy of one reference and two test products of lanthanum carbonate chewable tablets. Langmuir equation was utilized to calculate the binding constants k1 and k2 . The phosphate binding to the tablets of lanthanum carbonate product was pH dependent, with a faster binding rate at low pH. The crushed tablets bind phosphate more rapid. Compared with the whole tablets, the kinetic binding profiles from the crushed tablets were less variable under all conditions for both test and reference products. The phosphate level has a significant impact on the phosphate binding for both whole and crushed tablets under all pH conditions, with more binding at higher phosphate concentration. The phosphate binding profiles displayed significant difference among the products. For a crushed tablet, the phosphate binding to lanthanum reached equilibrium within 8 h under all conditions. The 90% confidence interval for the k2 ratio (test/reference) was well within the 80%-125% under all pH conditions. However, the k1 ratio varies from 54% to 144%. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:1370-1381, 2013., (Copyright © 2013 Wiley Periodicals, Inc.)
- Published
- 2013
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39. Spontaneous carbonate formation in an amorphous, amine-rich, polymeric drug substance: sevelamer HCl product quality.
- Author
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Berendt RT, Samy R, Carlin AS, Pendse A, Schwartz P, Khan MA, and Faustino PJ
- Subjects
- Calorimetry, Differential Scanning, Carbon Dioxide chemistry, Crystallization, Drug Stability, Magnetic Resonance Spectroscopy, Sevelamer, Thermogravimetry, Water chemistry, Carbonates chemistry, Chelating Agents chemistry, Polyamines chemistry
- Abstract
Spectral differences among multiple manufacturers/lots of sevelamer HCl were observed by Fourier transform infrared spectroscopy, and further characterization was performed to identify the cause for these differences. The drug substance is a polymer that possesses a large molecular weight, is amorphous, and is practically insoluble in both water and organic solvents. Thus, solid-state characterization methods (spectroscopic and thermal) were required to identify and characterize differences among the samples to assess possible differences in product quality. ¹³C cross-polarization-magic-angle-spinning nuclear magnetic resonance spectroscopy of sevelamer HCl substances demonstrated the presence of a carbonyl-containing species, which was attributed to a carbonate impurity among samples. Stability studies demonstrated that this carbonate impurity formed spontaneously upon exposure of the drug substance to atmospheric water vapor and carbon dioxide, even under ambient conditions. Mechanistically, this behavior likely arises from the large number of primary and secondary amine groups, the hygroscopicity of the HCl salt, and a high degree of molecular mobility due to the amorphous nature of the drug substance., (Copyright © 2012 Wiley Periodicals, Inc.)
- Published
- 2012
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40. Chemometric evaluation of brompheniramine-tannate complexes.
- Author
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Zidan AS, Rahman Z, and Khan MA
- Subjects
- Least-Squares Analysis, Principal Component Analysis, Regression Analysis, Spectroscopy, Near-Infrared, Spectrum Analysis, Raman, Brompheniramine chemistry, Histamine H1 Antagonists chemistry, Tannins chemistry
- Abstract
The objective of the current study was to evaluate the performance of Raman and near-infrared (NIR) techniques combined with chemometrics in characterizing the critical quality attributes of brompheniramine (BP)-tannate complexes. Seven complexes were prepared and evaluated for chemical interactions, solubilities, dissolutions, and spatial distributions by NIR chemical imaging (CI). Principal component analysis (PCA) was applied before either partial least squares regression (PLSR) or principal component regression (PCR) models were developed. Complexation was confirmed by Fourier transform IR analysis to yield complexes of lower drug solubilities and sustained-release characteristics in alkaline media. PCA results showed better discrimination ability by NIR than by Raman spectroscopy. Compared with PCR, the PLSR predictions errors, calculated from the Raman and NIR data with second-derivative pretreatment, showed lesser values of 2.68, 0.37, 1.79, and 5.60 and 0.58, 0.25, 0.93, and 0.58 for complex solubilities in acidic and alkaline media and percentages dissolved after 1 and 20 h, respectively. In addition, good correlation (>0.95) was obtained for predicting the drug concentration using PLSR score images explaining the validity of the NIR-CI model for spatial quantitation of BP within its tannate complexes. In conclusion, the chemometric analysis of NIR and/or Raman spectra represented an innovative approach to determine the tannate complexation variability., (Copyright © 2011 Wiley Periodicals, Inc.)
- Published
- 2012
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- View/download PDF
41. Quality-by-design: an integrated process analytical technology approach to determine the nucleation and growth mechanisms during a dynamic pharmaceutical coprecipitation process.
- Author
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Wu H and Khan MA
- Subjects
- Drug Compounding methods, Spectroscopy, Near-Infrared, Thermodynamics, Anti-Inflammatory Agents, Non-Steroidal chemistry, Chemical Precipitation, Naproxen chemistry, Polymethacrylic Acids chemistry
- Abstract
The objective of this study was to demonstrate the feasibility of using an integrated process analytical technology (PAT) approach to determine nucleation and growth mechanisms of a dynamic naproxen (drug)-Eudragit L100 (polymer) coprecipitation process. The influence of several thermodynamically important formulation and process variables (drug/polymer ratio, alcohol, and water usages) on coprecipitation process characteristics was investigated via real-time in situ focused beam reflectance measurement (FBRM) monitoring and near real-time particle vision microscopy measurement. The final products were characterized by near-infrared (NIR) spectroscopy and NIR chemical imaging microscopy. The coprecipitation nucleation induction time (t(ind) ) was measured by both FBRM trend statistics and process trajectory method, respectively. Furthermore, nucleation kinetics was evaluated based on t(ind) measurement and corresponding supersaturation ratio (S) estimated. It was found that plots of ln(t(ind) ) versus (ln(2) S)(-1) consist of two linear segments and are consistent with classical primary nucleation mechanisms. Apparently, the coprecipitation process is governed by heterogeneous primary nucleation mechanism at low S (14 ≤ S ≤ 503) and by homogeneous primary nucleation mechanism at high S (1216 ≤ S ≤ 3649). Off-line characterizations collectively supported this statement. Therefore, it demonstrated that integration real-time PAT process monitoring with first-principles modeling and off-line product characterization could enhance understanding to coprecipitation process dynamics and nucleation/growth mechanisms, which is impossible via off-line techniques alone., (Copyright © 2010 Wiley-Liss, Inc.)
- Published
- 2011
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42. Quality-by-Design (QbD): an integrated process analytical technology (PAT) approach for real-time monitoring and mapping the state of a pharmaceutical coprecipitation process.
- Author
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Wu H and Khan MA
- Subjects
- Absorption, Crystallization methods, Drug Compounding methods, Models, Chemical, Naproxen chemistry, Nephelometry and Turbidimetry methods, Polymethacrylic Acids chemistry, Principal Component Analysis methods, Quality Control, Chemical Precipitation, Drug Industry methods, Technology, Pharmaceutical methods
- Abstract
In this work, an integrated PAT approach was developed for monitoring a pharmaceutical (naproxen) and a polymer (eudragit) coprecipitation process: real-time in-line near-infrared (NIR) absorbance monitoring, real-time on-line turbidity monitoring, and in situ crystal size monitoring. The data and information obtained through these three monitoring techniques confirmed the observation of the onsets of three distinct stages: incubation, nucleation, and crystal growth. The process trajectory constructed based on results of applying principal component analysis (PCA) to either process NIR spectra data or process turbidity profile, clearly demonstrated that various distinguishable process events, including incubation, nucleation, and crystal growth, could be accurately tracked and differentiated. These findings were further supported by process knowledge and information, such as process design, process sequence, thermodynamic and mass-transfer analysis. Therefore, this work provides a case study that illustrated a rational approach to develop a science-based and knowledge-based process monitoring strategy, which is essential for establishing both a suitable process control strategy and an operational process space for a pharmaceutical unit operation., (2009 Wiley-Liss, Inc. and the American Pharmacists Association)
- Published
- 2010
- Full Text
- View/download PDF
43. Spectral and spatial characterization of protein loaded PLGA nanoparticles.
- Author
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Zidan AS, Rahman Z, Habib MJ, and Khan MA
- Subjects
- Chemistry, Pharmaceutical methods, Cyclosporine chemistry, Drug Carriers chemistry, Drug Compounding methods, Emulsifying Agents chemistry, Models, Statistical, Particle Size, Polylactic Acid-Polyglycolic Acid Copolymer, Proteins chemistry, Solvents chemistry, Lactic Acid chemistry, Nanoparticles chemistry, Polyglycolic Acid chemistry, Spectroscopy, Near-Infrared methods, Technology, Pharmaceutical methods
- Abstract
The objective of this study was to evaluate near infrared (NIR) spectroscopy and imaging as approaches to assess drug contents in poly(dl-lactide-co-glycolide) (PLGA) based nanoparticles of a model protein, cyclosporine A (CyA). A 6-factors 12-runs designed set of experiments with Plackett-Burman (PB) screening was applied in order to examine the effects of drug loading (X(1)), polymer loading (X(2)), emulsifier concentration (X(3)), stirring rate (X(4)), type of organic solvent (X(5)), and ratio of organic to aqueous phases' volumes (X(6)), on drug entrapment efficiency (EFF). After omitting the factors with nonsignificant influences on EFF, a reduced mathematical relationship, EFF = 48.34 + 7.3X(1) - 29.95X(3), was obtained to explain the effect of the significant factors on EFF. Using two different sets for calibration and validation, the developed NIR calibration model was able to assess CyA contents within the 12 PB formulations. NIR spectral imaging was capable of clearly distinguishing the 12 formulations, both qualitatively and quantitatively. A good correlation with a coefficient of 0.9727 was obtained for constructing a quantile-quantile plot for the actual drug loading percentage and the % standard deviation obtained for the drug loading prediction using the hyperspectral images., (2009 Wiley-Liss, Inc. and the American Pharmacists Association)
- Published
- 2010
- Full Text
- View/download PDF
44. Thermodynamic stability assessment of a colloidal iron drug product: sodium ferric gluconate.
- Author
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Yang Y, Shah RB, Faustino PJ, Raw A, Yu LX, and Khan MA
- Subjects
- Calibration, Chemistry, Pharmaceutical, Chromatography, Gel, Colloids, Drug Stability, Ferric Compounds standards, Hydrogen-Ion Concentration, Molecular Structure, Molecular Weight, Quality Control, Reference Standards, Ferric Compounds chemistry, Thermodynamics
- Abstract
A high performance gel permeation chromatography (HP-GPC) method was developed, validated and used to determine the molecular weight (MW) of sodium ferric gluconate following various stress conditions. The intra-day accuracy (90-103%), intra-day precision (1.5-2.7%), inter-day accuracy (91-105%), inter-day precision (1.3-3.2%) were within acceptable range stated in FDA guidance. The MW of sodium ferric gluconate remained unchanged after: (1) autoclaving (121 degrees C), (2) moderate thermal stress (30 days at 50 degrees C or 7 days at 70 and 90 degrees C), (3) excipient dilution, (4) basic buffer dilution (pH of 8 and 9), (5) ultracentrifugation, (6) dialysis, and (7) electrolyte dilution. However sodium ferric gluconate showed signs of instability at higher temperatures (>90 degrees C) after 30 days and at pH of 10-11. Sodium ferric gluconate was found to be a lypophilic colloidal solution with an average particle size of 10 nm and a zeta potential of -13 mV. The colloid osmotic pressure was 3.5 mmHg and remained unchanged after moderate thermal stress. Additionally, in-house drug products with similar MW to sodium ferric gluconate were produced by three different synthetic procedures, suggesting that this colloidal iron drug product might be thermodynamically stable.
- Published
- 2010
- Full Text
- View/download PDF
45. Quality-by-design (QbD): an integrated approach for evaluation of powder blending process kinetics and determination of powder blending end-point.
- Author
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Wu H and Khan MA
- Subjects
- Drug Evaluation, Preclinical methods, Drug Evaluation, Preclinical standards, Quality Control, Spectroscopy, Near-Infrared methods, Spectroscopy, Near-Infrared standards, Chemistry, Pharmaceutical methods, Chemistry, Pharmaceutical standards, Endpoint Determination methods, Endpoint Determination standards, Powders chemical synthesis, Powders pharmacokinetics
- Abstract
The objective of this study was to develop an integrated process monitoring approach for evaluating powder blending process kinetics and determining blending process end-point. A mixture design was created to include 26 powder formulations consisting of ibuprofen as the model drug and three excipients (HPMC, MCC, and Eudragit L100-55). The mixer was stopped at various time points to enable near-infrared spectroscopy scan of the powder mixture for obtaining the time course of the blending process. The evaluation of the blending process kinetics and process end-point was studied through three quantitative approaches: (1) Spectra linear superposition method; (2) Characteristic peak method; (3) Moving block standard deviation method. It was found that the powder blending experienced an initial rapid process to reach a quasi- end point within the first few minutes. Afterwards, a demixing occurred. Then, a real blending end-point was reached as characterized by an inflection point. ANOVA shows that the compositions of ibuprofen and MCC are the most statistically significant variables that impact the time required to reach the blending end-point. This highlighted the critical importance of developing quantitative chemometric approaches to extract critical process information and generate essential process knowledge to enable real-time release of the blending process., (Copyright 2009 Wiley-Liss, Inc.)
- Published
- 2009
- Full Text
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46. Robust calibration design in the pharmaceutical quantitative measurements with near-infrared (NIR) spectroscopy: Avoiding the chemometric pitfalls.
- Author
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Xiang D, Berry J, Buntz S, Gargiulo P, Cheney J, Joshi Y, Wabuyele B, Wu H, Hamed M, Hussain AS, and Khan MA
- Subjects
- Calibration, Hardness Tests, Least-Squares Analysis, Models, Theoretical, Multivariate Analysis, Reproducibility of Results, Spectroscopy, Near-Infrared methods, Tablets chemistry
- Abstract
Quantification analysis with near-infrared (NIR) spectroscopy typically requires utilizing chemometric techniques, such as partial least squares (PLS) method, to achieve the desired selectivity. This article points out a major limitation of these statistical-based calibration methods. The limitation is that the techniques suffer from the potential for chance correlation. In this article, the impact of chance correlation on the robustness of PLS model was illustrated via a pharmaceutical application with NIR to the content uniformity determination of tablets. The procedure involves evaluating the PLS models generated with two sets of calibration tablets incorporated with distinct degree of concentration correlation between the active pharmaceutical ingredient (API) and excipients. The selectivity and robustness of the two models were examined by using a series of data sets associated with placebo tablets and tablets incorporated with variations from excipient content, hardness and particle size. The result clearly revealed that the strong correlation observed in the PLS model created by the correlated design was not solely based on the API information, and there was an intrinsic difference in the variances described by the two calibration models. Diagnostic tools that enable the characterization of the chemical selectivity of the calibration model were also proposed for pharmaceutical quantitative analysis., ((c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association)
- Published
- 2009
- Full Text
- View/download PDF
47. Functionality of magnesium stearate derived from bovine and vegetable sources: dry granulated tablets.
- Author
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Hamad ML, Gupta A, Shah RB, Lyon RC, Sayeed VA, and Khan MA
- Subjects
- Animals, Cattle, Excipients, Stearic Acids chemistry, Stearic Acids administration & dosage, Tablets, Vegetables chemistry
- Abstract
Magnesium stearate is a functional excipient used to ensure efficient ejection of tablets. This study compares the functionality of a vegetable and bovine grade of magnesium stearate. Tablets were prepared by direct compression and dry granulation of a model formulation. Physical and chemical tests were performed on bulk powders, granule intermediates, and finished tablets to provide a comprehensive comparison of the two grades of magnesium stearates. Raw material characterization of the two grades showed no difference in particle size, surface area, true density, and total moisture content. However, significant differences in fatty acid composition, surface tension, and zeta potential were detected. Tablet ejection force for the physical mixture formulations was variable, showing similar ejection force for the two grades of magnesium stearate at some concentrations and different ejection forces at other concentrations. The dry granulated formulation containing vegetable-based magnesium stearate showed a lower ejection force than the formulation containing bovine-based magnesium stearate. There was no difference between the dissolution profiles of the tablets containing the two grades of magnesium stearate prepared by both methods. The results indicated that magnesium stearate interchangeability with respect to lubricant efficiency depends upon the level in which it is used and the manufacturing method.
- Published
- 2008
- Full Text
- View/download PDF
48. Quality-by-design (QbD): effects of testing parameters and formulation variables on the segregation tendency of pharmaceutical powder measured by the ASTM D 6940-04 segregation tester.
- Author
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Xie L, Wu H, Shen M, Augsburger LL, Lyon RC, Khan MA, Hussain AS, and Hoag SW
- Subjects
- Analysis of Variance, Particle Size, Sensitivity and Specificity, Chemistry, Pharmaceutical, Pharmaceutical Preparations, Powders
- Abstract
The objective of this study was to examine the effects of testing parameters and formulation variables on the segregation tendency of pharmaceutical powders measured by the ASTM D 6940-04 segregation tester using design of experiments (DOE) approaches. The test blends consisted of 4% aspirin (ASP) and 96% microcrystalline cellulose (MCC) with and without magnesium stearate (MgS). The segregation tendency of a blend was determined by measuring the last/first (L/F) ratio, the ratio of aspirin concentrations between the first and last samples discharged from the tester. A 2(2) factorial design was used to determine the effects of measurement parameters [amount of material loaded (W), number of segregation cycles] with number of replicates 6. ANOVA showed that W was a critical parameter for segregation testing. The L/F value deviated further from 1 (greater segregation tendency) with increasing W. A 2(3) full factorial design was used to assess the effects of formulation variables: grade of ASP (unmilled, milled), grade of MCC, and amount of lubricant, MgS. MLR and ANOVA showed that the grade of ASP was the main effect contributing to segregation tendency. Principal Component Regression Analysis established a correlation between L/F and the physical properties of the blend related to ASP and MCC, the ASP/MCC particle size ratio (PSR) and powder cohesion. The physical properties of the blend related to density and flow were not influenced by the grade of ASP and were not related to the segregation tendency of the blend. The direct relationship between L/F and PSR was determined by univariate analysis. Segregation tendency increased as the ASP to MCC particle size increased. This study highlighted critical test parameters for segregation testing and identified critical physical properties of the blends that influence segregation tendency., ((c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association)
- Published
- 2008
- Full Text
- View/download PDF
49. Process analytical technology: nondestructive evaluation of cyclosporine A and phospholipid solid dispersions by near infrared spectroscopy and imaging.
- Author
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Zidan AS, Habib MJ, and Khan MA
- Subjects
- Calibration, Calorimetry, Differential Scanning, Drug Evaluation, Preclinical, Models, Theoretical, Spectroscopy, Fourier Transform Infrared, Cyclosporine chemistry, Dimyristoylphosphatidylcholine chemistry, Spectroscopy, Near-Infrared methods
- Abstract
The objective of this study was to evaluate near infrared (NIR) spectroscopy and imaging as approaches to assess phospholipid compartment within its solid dispersion with cyclosporine A (CyA). By varying dimyristoyl phosphatidylcholine (DMPC) to CyA weight ratio, five batches were prepared by the kneading technique and characterized by DSC and FTIR. A drug/DMPC ratio of 50:1 provided an enhanced dissolution of CyA. FTIR spectra and DSC thermograms revealed a significant interaction between the drug and DMPC which suggested incorporation of CyA within the formed DMPC liposomes. The developed NIR calibration model was able to assess DMPC concentrations within the kneaded products. The calibration and prediction linear plots showed slopes of 0.9711 and 0.9915, offsets of 0.1247 and 0.1080, correlation coefficients of 0.9854 and 0.9889 and root mean square standard errors of 0.43% and 0.42%, respectively. In contrast, NIR spectral imaging was capable of clearly distinguishing the kneaded products, both qualitatively and quantitatively. NIR imaging revealed the poor powder blending efficiency of the method used to prepare physical mixture compared to the efficient distribution of the kneaded products. In conclusion, NIR spectral imaging system provides a rapid approach for acquiring high-resolution spatial and spectral information on solid dispersions.
- Published
- 2008
- Full Text
- View/download PDF
50. Process analytical technology (PAT): quantification approaches in terahertz spectroscopy for pharmaceutical application.
- Author
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Wu H, Heilweil EJ, Hussain AS, and Khan MA
- Subjects
- Algorithms, Calibration, Multivariate Analysis, Excipients analysis, Spectrum Analysis methods, Tablets analysis, Technology, Pharmaceutical methods
- Abstract
Terahertz (THz) spectroscopy and chemometric analysis of resultant absorption spectra in the 30-500 cm(-1) range has been applied to perform quantitative determination of both active ingredient and excipient concentrations of tablets. Tests were performed on a series of tablets composed of various concentrations and processes of theophylline formulated with lactose, magnesium stearate, starch or Avicel, and as a function of tablet hardness. Transmission spectra of polyethylene pellets derived from each of the samples were analyzed using three approaches. Spectral superposition method was used as an indirect measure to examine whether and when the interaction among various pharmaceutical components and the tableting history could be considered insignificant for quantification purpose. Spectral characteristic peak method was able to correlate peak maxima with correction for tablets having the same hardness. Multivariate analysis (PCR and PLS 1) was capable of correlating THz spectra with tablet concentrations. The predicted concentrations of independent samples using multivariate models agreed well with nominal concentrations. The best correlations were obtained using multivariate analysis. With these studies, the advantage of using multivariate approach was demonstrated for process analytical technology (PAT) application. Further, the feasibility of integrating THz spectroscopy and chemometrics for the purpose of quantifying pharmaceutical tablet concentrations was demonstrated.
- Published
- 2008
- Full Text
- View/download PDF
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