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Background and purpose: Urate crystal accumulation may lead to the condition of ocular tophaceous gout, causing ocular inflammation and increased intraocular pressure (IOP) due to the triggering of several inflammatory receptors like NLRP3, A2A, and TLR4. The study has been undertaken to manage intraocular pressure and inflammation using febuxostat (FBX) film formulation for sustained and improved activity, particularly for long-term tophaceous gout patients. Experimental approach: Hydroxypropyl methyl-cellulose K100 matrix-based hydrogel film of FBX has been fabricated in the presence of plasticizers like triethanolamine, dimethyl-sulphoxide (DMSO), or polyethylene glycol 600 using casting and evaporation technique. Carrageenan was injected into the upper palpebral region to induce ocular inflammation, and a normotensive rabbit eye model was used for monitoring IOP. Key results: Amorphization of the drug was observed from the differential scanning calorimetry and X-ray diffraction results. In vitro release study revealed an improved and diffusion-controlled sustained drug release for more than 5 h (62.69 to 84.76 %). Compared to its absence, decreased IOP was extended up to 5 h using film (with DMSO). Disappearance of ocular inflammation was also observed in the test animals after 2.5 h of film application, whereas acute inflammation was continued in the group without treatment for more than 4 h. Docking study revealed good binding interaction of drug and NLRP3, A2A, and TLR4 receptor. Conclusion: Febuxostat-loaded hydrogel-forming plasticized film could be utilized to better manage and control ocular inflammation and associated IOP, particularly in ocular tophaceous gout patients.

Hydration behavior of hydrogel-based polymeric film possesses great importance in mucosal drug delivery. Modified Lag phase sigmoid model was used for the investigation of hydration of the film. Kaolin incorporated HPMC K100LVCR (HL) and K100M (HH) films containing dexamethasone as a model drug have been prepared for studying swelling kinetics. Swelling of HL and HH films was decreased with the gradual increase of kaolin content and HH of higher viscosity has shown higher value than HL matrix. Kaolin also inhibited the film erosion process. Mathematically modified lag phase sigmoid model demonstrated similarity of the predicted swelling content with the observed value. High R2 and small RMSE value confirmed the successful fitting of the modified lag phase sigmoid model to the experimental data of swelling content. τ value similar to the observed one was obtained. This modified model could be reliable enough for estimating hydration process in food grains, food packaging films etc.

Titanium dioxide can adhere with human epithelial cells and have good tolerability. Present work has been undertaken to explore the influence of TiO2 on mucosal permeation of aceclofenac. Mucosal permeation of aeclofenac solution containing TiO2 has been carried out. In fourier transform infrared spectrosopy (FTIR), the intensity of the peaks has decreased along with the increase of TiO2 content in the formulation indicating a possible binding between drug and TiO2. Melting enthalpy has been decreased with the increased content of TiO2 in the solid. The status of crystal strain and dislocation density of TiO2 and aceclofenac in the solid state formulation has also been evaluated from Xray Diffraction data using Debye-Scherrer’s equation. Mucosal permeation of aceclofenac has shown sustained effect for more than 20 h in presence of titanium dioxide. Titanium dioxide could be used in designing formulation for sustaining mucosal aceclofenac delivery after performing risk assessment study.

Despite of the clinical, scientific, and commercial development, many patients complain about pain on the intravenous injection of propofol. Present work was undertaken to develop a stable multi-dose propofol nano-emulsion using 32 full factorial design which is supposed to be associated with less anticipated pain during intravenous administration. Propofol was incorporated in the mixture of disodium edetate, sodium oleate, thioglycerol, glycerol, egg lecithin, soyabean oil and medium chain triglyceride oil, and homogenization was continued at controlled temperature of 20 °C. The product did not show any significant change in visible extraneous particulate matter, pH, osmolality, bacterial endo-toxin, sterility, high performance liquid chromatography (HPLC) their stability and impurities after exposing at 40 °C for 3 and 6 months. Homogenization at 850 bar pressure of 30 min duration produced 174 nm particles with –53.6 mV zeta potential indicating its stability.

Analysis of the binding interactions of ibuprofen and silicified-microcrystalline cellulose (SMCC) has been undertaken. Co-processing of ibuprofen with SMCC was carried out by solid state ball milling, and aqueous state equilibration followed by freeze drying to investigate the effect of silicified-microcrystalline cellulose on ligand. Molecular docking study revealed that ibuprofen formed complex through hydrogen bond with microcrystalline cellulose (MCC) and silicon dioxide (SiO2); the binding energy between MCC and SiO2, and ibuprofen and SMCC were found as -1.11 and -1.73 kcal/mol respectively. The hydrogen bond lengths were varying from 2.028 to 2.056 Å. Interaction of Si atom of SMCC molecule with Pi-Orbital of ibuprofen has shown the bond length of 4.263 Å. Significant improvement in dissolution of ibuprofen has been observed as a result of interaction. Binary and ternary interactions revealed more stabilizing interactions with ibuprofen and SMCC compared to SMCC formation.

Assessment of interactions of ibuprofen and magnesium trisilicate after co-processing has been carried out by infrared spectroscopy. Dry-state ball-milling and, aqueous state kneading and freeze-drying were performed. FTIR spectroscopy of co-processed materials described acid–base reaction between the carboxylic acid containing ibuprofen to a significant extent. Increased absorbance of carboxylate peak accompanied by a consistently reduced absorbance of the carbonyl acid peak was evident. Absorbance of carboxylate peak was more in freeze-dried sample compared to milled product. Intermolecular hydrogen bonding between ibuprofen and magnesium trisilicate in the co-processed material has been suggested. Inhibition of crystal morphology has been noticed in the photomicrographs of both the products. DSC report has shown absence or significantly decreased melting endotherm representing almost complete amorphization of ibuprofen. Release of drug increased greatly after co-processing in comparison to crystalline ibuprofen. Freeze-dried samples have improved drug release more significantly compared to ball-milled samples.

Background and objective: There has been relatively little investigation of the effect of temperature on skin permeation compared to other methods of penetration enhancement. A principal physicochemical factor which controls the passive diffusion of a solute from a vehicle into the skin arises from the skin temperature. The aim of this ex vivo study was to probe into the effect of heat on transdermal absorption of alfuzosin hydrochloride from ethyl cellulose-polyvinyl pyrrolidone (EC-PVP) based transdermal systems. Materials and methods: Principles of design of experiment (DoE) were used to systematically study the influence of temperature on transdermal permeation of alfuzosin. Ex vivo transdermal permeation studies were carried out at varied donor compartment temperatures. Permeation data analysis was carried out and activation energy for transdermal permeation was estimated. Results: Temperature found to enhance ex vivo permeation parameters of alfuzosin hydrochloride from its transdermal systems. It was also noted that chemical permeation enhancers potentiate permeation enhancing effect of temperature. The permeation flux values approximately doubled after exposure to 45 °C. The activation energy for transdermal permeation was found lower for the runs with chemical permeation enhancers indicating existence of a lower energy barrier in the presence of chemical permeation enhancers. Conclusion: The method reported here is a simple and useful tool for studying the effect of heat on percutaneous absorption. Such temperature dependent enhancement of flux can be more pronounced at skin surface temperatures >45 °C.

Interaction and physicochemical characterization of dispersions of naproxen in calcium carbonate after freeze-drying the wet-state equilibrated mixture have been investigated by analytical methods. The FT-IR study revealed the acid-base reaction between naproxen and calcium carbonate. The DSC study indicated physical interaction and significantly diminished crystallinity of naproxen in the formulation containing higher quantities of calcium carbonate. Furthermore, the SEM study showed the reduced particle size and loss of crystalline morphology in the same sample. Drug release increased with the increase of calcium carbonate in the formulations. Formulation of naproxen with calcium carbonate in 1:2 ratio allowed its dissolution to the greatest extent (94.96%) while other compositions, 1:0.5 and 1:1, showed 80.86% and 78.30% release, respectively.

Purpose: The main objective of the investigation was to develop a transdermal therapeutic system for alfuzosin hydrochloride and to study the effects of polymeric system and loading dose on the in vitro skin permeation pattern. Materials and methods: Principles of experimental design have been exploited to develop the dosage form. Ratio of ethyl cellulose (EC) and polyvinyl pyrrolidone (PVP) and loading dose were selected as independent variables and their influence on the cumulative amount of alfuzosin hydrochloride permeated per cm2 of human cadaver skin at 24 h (Q24), permeation flux (J) and steady state permeability coefficient (P SS) were studied using experimental design. Various physicochemical parameters of the transdermal films were also evaluated. Activation energy for in vitro transdermal permeation has been estimated. Results: Ratio of EC and PVP was found to be the main influential factor for all the dependent variables studied. Drug loading dose was also found to influence the dependent variables but to a lesser extent. Physicochemical parameters of the prepared films were evaluated and found satisfactory. Activation energy for alfuzosin permeation has also been estimated and reported. Conclusion: The therapeutic system was found to be dermatologically non-irritant and hence, a therapeutically effective amount of alfuzosin hydrochloride can be delivered via a transdermal route.

Purpose: The present investigation is aimed at comparing the pharmacokinetic profile (Bioavailability) of aspirin in tablet formulations, which were prepared by using different effervescent excipients such as citric acid and malonic acid. Materials and Methods: The relative bioavailability and pharmacokinetics of citric acid based aspirin effervescent tablet (Product A) and malonic acid based aspirin effervescent tablet (Product B) formulations were evaluated for an in-vitro dissolution study and in-vivo bioavailability study, in 10 normal healthy rabbits. The study utilized a randomized, crossover design with a one-week washout period between doses. Blood samples were collected at 0, 1, 2, 4, 6, 8, 12 and 24 hours following a 100 mg/kg dose. Plasma samples were assayed by High Performance Liquid Chromatography. T max , C max , AUC 0-24 , AUC 0- ∞, MRT, K a, and relative bioavailability were estimated using the traditional pharmacokinetic methods and were compared by using the paired t-test. Result: In the present study, Products A and B showed their T max , C max , AUC 0-24 , AUC 0- ∞, MRT, and K a values as 2.5 h, 2589 ± 54.79 ng/ml, 9623 ± 112.87 ng.h/ml, 9586 ± 126.22 ng.h/ml, 3.6 ± 0.10 h, and 0.3698 ± 0.003 h -1 for Product A and 3.0 h, 2054 ± 55.79 ng/ml, 9637 ± 132.87 ng.h/ml, 9870 ± 129.22 ng.h/ml, 4.76 ± 0.10 h, and 0.3812 ± 0.002 h -1 for Product B, respectively. Conclusion: The results of the paired t-test of pharmacokinetics data showed that there was no significant difference between Products A and B. From both the in vitro dissolution studies and in vivo bioavailability studies it was concluded that products A and B had similar bioavailability.

We have taken kinetic measurements of the hydrolytic degradation of cefixime, and have studied the effect of Captisol complexation and water-soluble polymers on that degradation. The phase solubility of cefixime in Captisol was determined. Kinetic measurements were carried out as a function of pH and temperature. High-performance liquid chromatography (HPLC) was performed to assay all the samples of phase-solubility analysis and kinetic measurements. Chromatographic separation of the degradation products was also performed by HPLC. FT-IR spectroscopy was used to investigate the presence of any interaction between cefixime and Captisol and soluble polymer. The phase-solubility study showed AL-type behaviour. The pH–rate profile of cefixime exhibited a U-shaped profile whilst the degradation of cefixime alone was markedly accelerated with elevated temperature. A strong stabilizing influence of the cefixime–Captisol complexation and hypromellose was observed against aqueous mediated degradation, as compared with povidone and macrogol. The unfavourable effect of povidone and macrogol may have been due to the steric hindrance, which prevented the guest molecule from entering the cyclodextrin cavity, whereas hypromellose did not produce any steric hindrance. [ABSTRACT FROM AUTHOR]

The objective of the present research was to develop fluconazole-loaded transferosomal bigels for transdermal delivery by employing statistical optimization (23 factorial design–based). Thin-film hydration was employed to prepare fluconazole-loaded transferomal suspensions, which were then incorporated into bigel system. A 23 factorial design was employed where ratios of lipids to edge activators, lipids (soya lecithin to cholesterol), and edge activators (sodium deoxycholate to Tween 80) were factors. Ex vivo permeation flux (Jss) of transferosomal bigels across porcine skin was analyzed as response. The optimal setting for optimized formulation (FO) was A= 4.96, B= 3.82, and C= 2.16. The optimized transferosomes showed 52.38 ± 1.76% DEE, 76.37 nm vesicle size, 0.233 PDI, − 20.3 mV zeta potential, and desirable deformability. TEM of optimized transferosomes exhibited a multilamelar structure. FO bigel's FE-SEM revealed a globule-shaped vesicular structure. Further, the optimized transferosomal suspension was incorporated into thyme oil (0.1% w/w)–containing bigel (TO-FO). Ex vivo transdermal fluconazole permeation from different transferosomal bigels was sustained over 24 h. The highest permeation flux (4.101 μg/cm2/h) was estimated for TO-FO bigel. TO-FO bigel presented 1.67-fold more increments of antifungal activity against Candida albicans than FO bigel. The prepared thyme oil (0.1% w/w)–containing transfersomal bigel formulations can be used as topical delivery system to treat candida related fungal infections. [ABSTRACT FROM AUTHOR]

Background: Macitentan blocks endothelin receptors in order to control the pulmonary arterial hypertension (PAH). Oral administration of macitentan is associated with painful urination and troubled breathing. Objectives: Formulated macitentan hydrogel film was used for examining the control of intraocular pressure, and the effect of surfactant and cosurfactant was studied. Methods: Macitentan ocular film formulation has been prepared in hydroxypropyl methylcellulose (HPMC) matrix system using different surfactant/co-surfactant system, and intraocular pressure was monitored on normotensive rabbit eyes after application in the cul-de-sac. Results: The solid state characterization of the film indicated amorphisation of macitentan and no issues regarding major incompatibility was observed. Combination of surfactant, co-surfactant and hydrophilic co-solvent systems in the said films markedly improved the drug release and mucosal tissue permeation. Presence of PEG and Transcutol significantly improved ex vivo corneal permeation of MP and MT respectively compared to other films. Transcutol (MT) exhibited greatest difference among the formulations by improving the vesicular bilayer fluidity and reducing the mucosal tissue barrier facilitating the transcorneal diffusion. A combination of diffusion and erosion control behavior was observed in drug release and corneal permeation of the films due to the balanced liquid penetration and polymeric chain relaxation rate. MP and MT films were used for further in vivo studies to achieve possible effective and prolonged control of intraocular pressure. In vivo study has revealed the reduction in intraocular pressure upto about 23 % when tested on normotensive rabbit model. The films has managed to lower the IOP upto 3 h. Conclusion: Developed macitentan hydrogel film containing Transcutol (MT) could have a high potential for the control and management of ocular hypertension after topical application. [ABSTRACT FROM AUTHOR]

The sensitivity of ornidazole towards UV light is one of the most crucial causes in the significant reduction of the therapeutic efficacy. The effect of eutectic–excipient on photodegradation of ornidazole in aqueous state under the exposure of UV light has been studied. Ornidazole–eutectics were prepared using benzoic acid, citric acid, and malic acid as the former molecule (all at 1:1 molar ratio). Kinetics of ornidazole degradation has been studied in the aqueous state in the presence of the eutectic former under the influence of UV light. The patterned photodegradation has also been compared in the presence of HPMC (1:1 weight ratio). A significant decrease in the first-order kinetics rate constant (K) was observed for the ornidazole–eutectic mixture as compared to the ornidazole alone in the aqueous state. FTIR, DSC, XRD, and SEM study of the formulated sample suggested in support of eutectic formation. The negative energy in the in silico docking score of the eutectic complex indicated additional suggestion towards the stable binding (− 1.5 to − 2.1 kcal/mol). [ABSTRACT FROM AUTHOR]

Investigation on the larvicidal potential of Elettaria cardamomum (L.) Maton rhizome extracts against filarial vector, Culex quinquefasciatus Say, was undertaken with crude concentrations 0.1-0.5 per cent and 40, 50, and 60 ppm of each of petroleum ether, hexane and ethyl acetate rhizome extracts revealed that first instar larvae were most susceptible to crude rhizome extract with 100 per cent mortality at 0.5% after 24 hrs of exposure. Among three solvent extracts, ethyl acetate extract showed maximum mortality (96.66±3.33%) at 60 ppm after 72 hrs of exposure. LC50 values of larvicidal bioassays by crude rhizome extract were 0.1002, 0.0794, 0.1275 and 0.6334 ppm for 1st, 2nd, 3rd and 4th instars larvae after 72 hrs of exposure, respectively and LC50 values for larvicidal bioassays by petroleum ether, hexane, and ethyl acetate rhizome extracts were 48.3629, 40.9613 and 37.0282 ppm against 3rd instar larvae after 72 hrs of exposure, respectively. Preliminary phytochemical analyses of the rhizome extracts showed presence of secondary metabolites. Non target organisms, tadpoles of frog and 4th instar larvae of Chironomus circumdatus, were not affected by the crude as well as ethyl acetate rhizome extracts. Larvicidal efficacy of the rhizome extracts of E. Cardamomum against Cx. quinquefasciatus mosquito species has been reported first time. [ABSTRACT FROM AUTHOR]

Vildagliptin (VID) is a dipeptidyl peptidase-4 (DPP-4) inhibitor used in controlling blood glucose level in type 2 diabetes. Vildagliptin improves beta cells function and is also suggested to effectively control the inflammation. The possible ocular anti-inflammatory property of vildagliptin has been explored using topically applied plasticized ocular film formulation. Film formulation was prepared by solvent cast and evaporation method using triethanolamine (TEA), dimethyl sulphoxide (DMSO), and polyethylene glycol 400 (PEG 400) as the plasticizer in HPMC hydrogel matrix base. Anti-inflammatory study was carried out in the carrageenan induced ocular rabbit model. Analytical methods confirmed that the drug was present almost in completely amorphized form in the film formulation. Level of hydration, swelling and erosion rate of the film played the controlling factor in the process of drug release, ocular residence and permeation. Maximum swelling rate of 363 h−1 has been shown by VHT compared to other formulation of VHD and VHP (174 and 242 h−1 respectively). Film containing DMSO exhibited highest in vitro release as well as ex vivo ocular permeation. Film formulation has shown a fast recovery of ocular inflammation in contrast to the untreated eye after inducing inflammation. Plasticized vildagliptin hydrogel film formulation could be utilized in the management and control of ocular inflammation particularly with diabetic retinopathy after proper clinical studies in higher animal and human individuals. [ABSTRACT FROM AUTHOR]

The global pandemic of COVID-19 is progressing rapidly across the world and declared as health emergency. The novel Coronavirus can cause severe lower respiratory tract infections primarily in geriatric, immunocompromised persons, infants and patients with comorbidities, or genetic disorders. Few Emergency Use Authorizations (EAUs) have been granted by FDA and other regulatory bodies with an aim to repurpose the existing approved medicines to fight the disease, and till date no specific treatment methodologies or preventive measures are available. At present, numerous medications which are already approved for other therapeutic indications, as well as the new medications, are undergoing clinical trials for the evaluation of safety and efficacy against COVID-19 infection. These therapeutic ranges include antimalarial, antiviral, steroids, convalescent plasma containing antibodies, and immune modulators, etc. Nevertheless, the primary focus is on preventive care and currently more than hundred potential vaccine candidates are under development by leading biotech companies across the globe which are at different phases of clinical development. Lipid based mRNA delivery, DNA delivery and mAbs are the most advanced technologies being embraced besides whole-virion inactivated vaccine, attenuated live vaccine, non-replicating viral vector-based vaccine, protein single unit vaccine and multiunit vaccine. This review focuses on the current progress in drug delivery systems of COVID-19 vaccine across industries, academics, and government funded research institutes with a special focus on the synthetic mRNA-based lipid nanoparticle (LNP). [ABSTRACT FROM AUTHOR]

Purpose: Oral drug delivery system has always been a preferred choice for the treatment of peptic ulcer and gastroesophageal reflux diseases. Being a proton pump inhibitor omeprazole restricts gastric acid secretion but the foremost downside is its degradation in acidic environments. The systemic absorption of gastro-unstable drugs can be improved by the enteric coating. Materials and Methods: This study was aimed at developing an effective enteric coating for omeprazole tablets using HPMC E5-LV and Hydroxypropyl Methylcellulose Acetate Succinate (HPMC-AS) polymers. The core tablets were subcoated with HPMC E5-LV which acted as a barrier between core tablet and enteric coated tablet. The enteric coating was applied using HPMC-AS. Results: Dissolution information unveiled that the enteric coat remained in place for 2 hr in acidic medium (0.1N HCl) and later dissolved when came in contact with basic media (acetate buffer pH 6.8), it dissolved within a jiffy. Conclusion: The release profile showed 91 to 98% drug release within 1hr in pH 6.8 Acetate buffer. Further instrumental analysis was performed to ascertain drug-polymer interaction. [ABSTRACT FROM AUTHOR]

Lamotrigine, a FDA approved antiepileptic drug is widely used in the treatment of epilepsy and bipolar disorder. However, poor aqueous solubility and low dissolution rate limit its oral absorption leading to a delayed onset of action with reduced therapeutic effect. The present study aims for the development of formulation and characterization of lamotrigine-salicylic acid crystalline product for the improvement of oral release and absorption for better management of epilepsy. The crystalline product of LT are developed with SA at 1:1, 2:1, 3:1 molar ratios by solvent evaporation method. The experimental crystals have been characterized by different analytical techniques such as fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) etc. Presence of characteristic peaks for peptide in the experimental crystalline products in FTIR spectra indicates formation of strong covalent bond between LA and SA. In the DSC thermograms, melting endotherm of the formulations showed different melting points than pure LT. PXRD data depicted sharp peaks for the formulations, which further justified the successful formation of a new crystalline phase. Dissolution profile of the experimental crystal (L1S1 at 1:1 molar ratio) in simulated gastric fluid was higher than that of the pure drug and other formulations. The optimized crystalline product of LT may be used for the better oral treatment of epilepsy with early onset of action after successful in vivo studies. [ABSTRACT FROM AUTHOR]

The crystallization technique has been established as a cost-effective and simple approach to improve the dissolution rate and oral bioavailability of poorly soluble drugs. This study was carried out to study the effect of some selected hydrophilic polymers such as methyl cellulose, hydroxypropyl methylcellulose (HPMC), polyvinyl alcohol, and carboxymethyl cellulose on the crystal behavior and dissolution properties of celecoxib (CLX), a common nonsteroidal anti-inflammatory drug. Structural and spectral characteristics of crystallized CLX have been studied by Fourier transform infrared (FTIR) spectroscopy, diffraction scanning calorimetry (DSC), and X-ray diffraction (XRD) analysis. From FTIR and DSC analysis, no significant shifting of peaks or appearance of any new peaks (for polymers) were observed, which indicated the absence of any major interaction between drug and polymers as well as the absence of polymers in the final crystallized product of CLX. The XRD analysis showed a change in crystalline morphology to some extent. The dissolution rate of crystallized CLX in the presence of polymers (particularly with HPMC) was significantly improved compared with plain CLX. The improved dissolution profile of the experimental CLX crystal products could be an indication of improved bioavailability of CLX for better clinical outcome. [ABSTRACT FROM AUTHOR]

Recent developments and collaborations of pharmaceutical manufacturers, hospitals, and government funded research bodies using 3D printing technology have been highlighted for the management of the healthcare crisis. 3D printing is a process of converting virtual 3D models developed by computer aided design into physical forms upon addition of material layer-by-layer (also known as additive manufacturing). This 3D printing is supposed to revolutionize significantly the healthcare system in the coming years. This process involves a tailored deposition of biomaterials layer by layer such as polylactic acid (PLA), polyvinyl alcohol (PVA), or other suitable pharma-grade polymers, copolymers, and their combinations to formulate three-dimensional custom designs with controlled architecture and composition. Food and Drug Administration (FDA) is currently thinking on regulation to ease the import restrictions for products intended for the detection and diagnosis of COVID-19 to ensure the timely availability of test kits. [ABSTRACT FROM AUTHOR]

Objectives: Polylactic acid (PLA) and copolymer polylactic-co-glycolic acid (PLGA) are the most versatile drug carriers for long acting release injectable (LAI) formulations for small molecules, peptides and macromolecules such as proteins and nucleic acids. The present research work consists of a PLGA based one-month release microsphere formulation of GnRH agonist leuprolide acetate, using double emulsion (W1/O/W2) technique. Materials and Methods: Microparticles were prepared by double emulsion solvent evaporation technique and critical quality attributes of finished products such as drug loading, entrapment efficiency, particle size distribution (PSD), surface porosity, drug distribution within microparticles were analysed. Results and Conclusion: The microspheres have shown the mean particle size of 15.2 μm and suitable particle size distribution pattern ideal for syringe ability. The microparticles were spherical in shape with uniform pore distribution and uniform distribution of API in the polymer matrix. The drug release has been sustained over a month for the microsphere formulation and could be correlated with the testosterone suppression. [ABSTRACT FROM AUTHOR]

Purpose: The present investigation was undertaken to study the effect of different plasticizers on the drug delivery pattern of valsartan from tamarind gum based hydroxypropyl methylcellulose (HPMC K100) transdermal film formulation. Methods: The matrix films of valsartan were prepared by casting solvent evaporation method using triethanolamine, propylene glycol, dimethyl sulphoxide, polyethylene glycol 400 or polyethylene glycol 600 as plasticizers. Physicochemical characteristics have also been evaluated using FTIR, DSC and SEM studies. Results: Instrumental studies revealed no major drug-excipience interaction. Amorphization of drug have been noticed in all the film formulations. A significant difference of drug diffusion as well as permeation between the formulations has been observed due to the presence of different plasticizers. This study confirmed that plasticizer cotributed a major role in developing a drug delivery system in tamarind based HPMC transdermal film. Conclusion: Highest area under the curve of the drug diffusion and ex vivo permeation profiles has been assured with the PEG 600 containing film up to 24 h of study. Hence, transdermal film formulation could be designed using different plasticizer in tamarind based HPMC matrix system as per requirements. [ABSTRACT FROM AUTHOR]

Background: Tablet manufacturing with direct compression is one of the leading industrial technique that consumes less time, labour and economic also. But the choice of excipients are critical in this case which will allow the drug to get compressed without granulation techniques. Purpose: Aceclofenac is a BCS class II non-steroidal anti-inflammatory drug, which exerts a low oral bioavailability because of low solubility in aqueous medium. The drug also suffers from compressibility and also shows poor tabletibility. Methods: We have attempted to improve tabletability by incorporating titanium dioxide (TiO2) through kneading and solvent evaporation technique. Results: In the FTIR study revealed that NH and Cl aromatic stretching of aceclofenac has been affected significantly due to binding with TiO2. DSC thermogram ascertained the partial amorphization of the drug in the formulations. Evaluated tabletability from the area under the applied pressure vs tensile strength curve (AUTC) of A1T1 has shown a poor value in contrast to other formulations. [ABSTRACT FROM AUTHOR]

Background and Objectives: Ornidazole is widely used as an antiprotozoal and antiamoebic drug and its onset of action is within 2 h. The major extent of the drug is metabolized in the liver and excreted in the urine and faeces. Hence, the present study of suppository formulation for sustained systemic delivery of ornidazole is significant which could minimize abdominal disturbances and nausea and delayed onset of action particularly after oral administration. Methods: Bioadhesive suppository formulations were prepared for systemic delivery of ornidazole via rectal and vaginal route. Results: The physical drug-excipient-interaction was confirmed by in-silico docking study. The affinity between drug-HPMC and drug-PEG was found to be -2 and -0.9 k cal/mol respectively. In vitro drug release of the suppositories varied depending on the viscosity grade of HPMC used and all have followed mostly diffusion controlled mechanism. The formulation containing HPMC K100 showed the most sustained release of ornidazole in both the dissolution fluid of pH 7.4 and 4.5 (54.53 and 41.89% respectively after 360 min). Conclusion: In conclusion, present bio adhesive suppositories could be utilized for sustained systemic delivery of ornidazole via rectal and vaginal route. The findings of this work will contribute to the current knowledge and encourage future pre-clinical research. [ABSTRACT FROM AUTHOR]

Background: Poor oral bioavailability of mesalamine (Mes) is due to extensive metabolism in the intestinal epithelial cells in addition to the liver. Purpose: Improved mesalamine release by Hot-Melt Extrusion (HME) technique could be utilized for better management of Inflammatory Bowel Disease (IBD). Methods: Mes and hydrophilic polymers like Eudragit- EPO, KollidonVA-64 and PEG 6000 were hot-melt extruded using a co-rotating twin-screw laboratory extruder. Results: The minor shifting with significantly reduced intensity and disappearance of peak in the Differential Scanning Calorimetry (DSC) thermogram could be attributed to some solid-solid interaction and not necessarily any incompatibility. Fourier-Transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM) confirmed the transformation of individual drug crystal into accumulations of small crystallites due to partial or almost complete amorphization. Continuous manufacturing of stable amorphous solid dispersion by solvent-free drug loading Hot-melt extrusion technique has been found feasible in improving drug release compared to mesalamine alone in simulated gastric fluid (f1= 0.3 to 11.1 and f2 = 26 to 49). Conclusion: Melt dispersion samples have exhibited significantly improved mesalamine release and could be utilized for better management of Inflammatory Bowel Disease (IBD). [ABSTRACT FROM AUTHOR]

Purpose: Kaolin can adhere to the mucosa and protect it by absorbing toxins, bacteria, and viruses. Ocular delivery and anti-inflammatory activity of dexamethasone hydrogel system could be advantageous after kaolin incorporation. Methods: Hydroxypropyl methylcellulose (HPMC) films of dexamethasone have been prepared without and with kaolin by solvent casting method. Differential scanning calorimetry (DSC), X-ray diffractometry (XRD), and scanning electron microscopy (SEM) were utilized for evaluating thermal property, crystallinity, and morphology of the film preparations respectively. In vitro drug release and corneal permeation ex vivo were carried out in phosphate buffer saline of pH 7.4 (PBS) at 34 ± 0.5°C for 6 h. Anti inflammatory effect of the prepared film was evaluated using carrageenan induced rabbit eye. Results: Disappearance of melting endotherm in the DSC thermogram is the indication of almost complete amorphization of drug in all the films. High-intensity reflections with characteristic peaks of pure drug crystal have resulted extensively reduced ordering of the crystal lattice in the X-ray pattern of all the films. Photomicrographs revealed that the plate-shaped geometry of the drug crystal has almost been lost in absence and presence of the nano-kaolin particles in the films. Kaolin incorporation controlled the drug release up to 6 h. Ocular permeation was diffusion controlled and extended for 6 h or more without exhibiting significant “Burst effect”. Adsorption of drug onto the surface of nano-kaolin prolonged the permeation due to cation exchange and hydrogen bonding. Signs of inflammation of the carrageenan induced rabbit eye have been disappeared almost completely after 2 h of film application. Conclusions: Local controlled delivery sustained anti-inflammatory activity of dexamethasone has been achieved using kaolin incorporated HPMC film. [ABSTRACT FROM AUTHOR]

The solvent evaporation of ibuprofen, Avicel, and Aerosil in selected ratios were evaluated for particle packing and rearrangement and drug release. Physicochemical characterization was carried out by using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). Transitional tapping between primary rearrangement and secondary rearrangement was found to be 20–30 taps with native ibuprofen powder and up to 45 taps with all formulated powders. Particle packing in the rearrangement stage was increased for all the formulations with respect to ibuprofen alone. Combination of Avicel and Aerosil brought about partial amorphization of the drug and improved wettability after solvent evaporation. Significantly improvement of packing of ibuprofen in rearrangement stage has been achieved by solvent evaporation of ibuprofen, Avicel, and Aerosil, which brought about improved release of drug from all formulated tablets. [ABSTRACT FROM PUBLISHER]

Context: A nonoral alternative such as transdermal system is desired to improve bioavailability and to maintain a constant and prolonged drug level with reduced frequency of dosing. Objective: The objective of the investigation is to develop a transdermal therapeutic system for alfuzosin hydrochloride and to study the influence of chemical permeation enhancers (CPEs) on the percutaneous permeation pattern. Material and methods: A D-optimal mixture design was used to study the influence of CPE with oleic acid (OA), lauric acid, and propylene glycol (PG) as mixture components. The influence of chemical enhancers on skin permeation was compared using one-way analysis of variance followed by multiple comparison analysis. Criterion of desirability was used to optimize the therapeutic system. Preclinical studies in rabbits were also carried out to establish an ex vivo--in vivo correlation (EVIVC). Results: The drug permeation pattern suggested Higuchian diffusion as predominant mode followed by case II to super case II transport as drug transport mechanism. The optimized formulation was obtained using 5%% (w//w) CPE consisting of a blend of 62.41%% OA and 37.59%% PG. About twofold increase in alfuzosin permeation was achieved with the optimized transdermal patch. An approximate linear EVIVC was established ( R2 == 0.971). Discussion: The optimized blend of enhancers could improve skin permeation parameters. A higher extent of in vivo skin permeation compared with cadaver skin permeation may be due to more permeable nature of rabbit skin. Conclusion: The investigations suggest an effective alternative delivery strategy such as transdermal systems for alfuzosin hydrochloride. [ABSTRACT FROM AUTHOR]

The present investigation aims at development of pressure sensitive adhesive (PSA) based drug in adhesive type transdermal systems of ondansetron hydrochloride with higher permeation flux. The effect of mixture of two chemical permeation enhancers (oleic acid and lauric acid diethanolamide); and drug loading dose on the ex vivo human cadaver skin permeation from the transdermal patches has been investigated using a -optimal combined mixture design. Incorporation of chemical permeation enhancers significantly improved the permeability parameters and it was also found that blend of permeation enhancers is more effective than either permeation enhancer. Criterion of desirability was employed to numerically optimize the transdermal system. Optimized formulation was achieved with 67.5% lauric acid diethanolamide, 32.5% oleic acid and 10% drug loading in an acrylate based PSA matrix. Optimized formulation was found to be nonirritating and safe for dermatological application. [ABSTRACT FROM AUTHOR]

In the present investigation, controlled release gastroretentive floating drug delivery system of theophylline was developed employing response surface methodology. A 32 randomized full factorial design was developed to study the effect of formulation variables like various viscosity grades and contents of hydroxypropyl methylcellulose (HPMC) and their interactions on response variables. The floating lag time for all nine experimental trial batches were less than 2 min and floatation time of more than 12 h. Theophylline release from the polymeric matrix system followed non-Fickian anomalous transport. Multiple regression analysis revealed that both viscosity and content of HPMC had statistically significant influence on all dependent variables but the effect of these variables found to be nonlinear above certain threshold values. [ABSTRACT FROM AUTHOR]

This present study is a preliminary exploration of the affinity between a carboxylic model drug ibuprofen and aluminum hydroxide. Ibuprofen was comilled with aluminum hydroxide in different weight ratios in the solid state and was characterized by scanning electron microscopy (SEM), X-ray powder diffractometry (XRD), Fourier transform infrared spectroscopy (FTIR), and in vitro dissolution studies. XRD and SEM studies indicated complete interaction of ibuprofen with aluminum hydroxide and complete amorphization of aluminum hydroxide-ibuprofen complexed salt as well, on comilling with aluminum hydroxide at 1:2 ratio. FTIR data showed the disappearance of acid carbonyl peak with the appearance and the corresponding increase in absorbance of new signal at 1,682 cm-1 in the 1:1 and 1:2 ibuprofen-aluminum hydroxide-comilled powder. The accompanied increase in the absorbance of carboxylate peak in the ibuprofen-aluminum hydroxide physical mixture, and 1:0.1, 1:0.5, 1:1, and 1:2 (IBApm, and IB1A0.1, IB1A0.5, IB1A1, and IB1A2, respectively) comilled powder indicated an acid-base reaction between ibuprofen and aluminum hydroxide. On storage at 40°C and 75% relative humidity (RH) for 10 weeks, XRD study showed the absence of reversion to the crystalline state and FTIR data revealed continued increase of new signal at 1,682 cm-1 relative to carboxylic acid peak and no reappearance of carboxylic acid peak. In vitro dissolution studies revealed that the percent release of ibuprofen from the aluminum hydroxide-comilled powder is in the following order: IB1A2 < IB1A1 < ibuprofen crystal < ibuprofen milled alone < IB1A0.1 < IB1A0.5. Aluminum metal cation might have interacted to form a complex through the carboxyl and carbonyl groups of ibuprofen. Improved dissolution of drug associated with IB1A0.1 and IB1A0.5 is because of the absence of a new signal at 1,682 cm-1 and improved amorphization of the drug to some extent. Dissolution of drug affected in IB1A2 and IB1A1 may be because of the insoluble stable complex formation. [ABSTRACT FROM AUTHOR]

This review focuses on the recent techniques of solubilization for the attainment of effective absorption and improved bioavailability. Solubilization may be affected due to cosolvent water interaction or altered crystal structure by cosolvent addition. Micellar solubilization could be affected by both ionic strength and pH. Addition of cosolvents to the surfactant solutions offers only a small advantage because of the decrease in the solublization capacity of the micelles. Polymorphism is known to influence dissolution and bioavailability of the drugs. Molecular modeling study of cyclodextrin inclusion complexations can predict the inclusion modes, stoichiometry of the complex, and the relative complexing efficiency of cyclodextrins with various drug molecules. [ABSTRACT FROM AUTHOR]

The interaction pattern of gatifloxacin was temperature-dependent Langmuir isotherm, and the Langmuir coefficients increased as the temperature was raised. The perturbation experiment conducted on this system showed that the nature of interaction was irreversible. The enthalpy change is a positive value, indicating the existence of increased activation energy as the temperature is raised. The entropy value, 24.21 e.u. obtained in this system, indicated that the hydration shells of the ions were rather tightly bound. Intestinal permeation study also revealed the decreased bioavailability of gatifloxacin relatively to the presence of aluminium hydroxide. The strong adsorption of gatifloxacin by aluminium hydroxide is due to formation of complexes with cations of aluminium hydroxide through carboxyl and carbonyl groups of gatifloxacin. [ABSTRACT FROM AUTHOR]

This chapter is a modified and extended version of the paper I presented at an international conference on ‘Sport, Culture and Society in Modern India’ held in Calcutta University in 2003. I am delighted to offer it as a part of the effort to celebrate the achievements of Professor. J.A. Mangan, who has shaped the course of the development of sports studies in South Asia. His keynote address at the department of history, University of Calcutta, in September 2003 inspired many social science students, with the result that sports studies is today formally a part of the postgraduate teaching curriculum in India. [ABSTRACT FROM AUTHOR]