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The on-site-treated effluent from an automobile manufacturing company is discharged into the public sewage system for further treatment. However, the upgrade of the treatment plant to reduce the effluent pollutant load led to the discharge limit for phenols being occasionally exceeded. The concern of the water authority prompted a study to investigate whether the toxicity of phenols could affect the performance of the receiving municipal wastewater treatment plant. To this end, mixtures of the industrial effluent and synthetic municipal wastewater were tested in a laboratory-scale activated sludge system. The bioreactor was fed with increasing ratios of the industrial wastewater in the combined influent (from 10 to 50%) over 7 months. No significant differences were observed in the system performance fed only with the synthetic wastewater (during the acclimation stage) or with the industrial wastewater. The bioreactor achieved average removal efficiencies of 70% for phenols even when half of the combined influent was the industrial wastewater. Bearing in mind the question of phenols, an important drawback was the high uncertainty in their determination by the conventional phenol index method due to the matrix effect. To overcome this a spectrophotometric procedure based on the serial dilutions of each pair of influent and effluent samples has been developed. Although strong microbial selection was observed by the changing bioreactor environment, the industrial effluent was found to be fully compatible with further treatment by conventional activated sludge process. [ABSTRACT FROM AUTHOR]

Given that interactions between the active principle and formulation excipients can modify the chemical composition, stability and bioavailability of a drug, thus compromising its effectiveness, the present study aims to evaluate the compatibility of Bromopride with commonly used pharmaceutical excipients, which has been characterized by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and powder X-ray diffraction. For such a purpose, samples of pure drug, 10 excipients and binary drug/excipient mixtures were analyzed in a ratio of 1:1 (m/m) by DSC, FTIR and high performance liquid chromatography (HPLC). DSC results reveal a probable interaction of Bromopride with the majority of excipients under study, except for mannitol and talc. The FTIR results indicate some interaction of BROM with all studied excipients. However, HPLC results reveal that only colloidal silicon dioxide, dicalcium phosphate dihydrated, magnesium stearate and microcrystalline cellulose were incompatible with Bromopride, as content reduction ranging between 16 and 42% was reached, and chemical interactions of excipients croscarmellose sodium, hydroxypropyl-methyl-cellulose, lactose monohydrate and polyvinylpyrrolidone with the API were not confirmed by the HPLC, despite the fact that they have been pointed out by the DSC and FTIR. The present study indicates that BROM undergoes interaction/incompatibility when mixed with colloidal silicon dioxide, dicalcium phosphate dihydrate, magnesium stearate, and microcrystalline cellulose. [ABSTRACT FROM AUTHOR]

The interactions between active pharmaceutical ingredients (APIs) and excipients may lead to API degradation, thereby affecting the safety and efficacy of drug products. Cbf-14 is a synthetic peptide derived from Cathelicidin-BF, showing potential for bacterial and fungal infections. In order to assess impurities in Cbf-14 gel, we developed a two-dimensional liquid chromatography coupled with quadrupole/time-of-flight mass spectrometric method. A total of eleven peptide degradation impurities were identified and characterized. Furthermore, the compatibility tests were conducted to evaluate the interactions of Cbf-14 with glycerol and methylcellulose, respectively. The results revealed that the impurities originated from condensation reactions between Cbf-14 and aldehydes caused by glycerol degradation. Several aldehydes were employed to validate this hypothesis. The formation mechanisms were elucidated as Maillard reactions between primary amino groups of Cbf-14 and aldehydes derived from glycerol degradation. Additionally, the compatibility of Cbf-14 with glycerol from different sources and with varying storage times was investigated. Notably, the interaction products in the gel increased with extended storage time, even when fresh glycerol for injection was added. This study offers unique insights into the compatibility study of peptides and glycerol, contributing to the ongoing quality study of Cbf-14 gel. It also serves as a reference for the design of other peptide preparations and excipients selections. [ABSTRACT FROM AUTHOR]

A good understanding of the physico-chemical characteristics of a drug substance and excipients is necessary to obtain a safe and effective drug dosage form. Based on the current recommendations of the regulatory agencies (EMA, FDA) regarding the implementation of the Quality by Design concept at the drug product development stage, this article is focused on the application of the experimental design approach at the preformulation studies. The purpose of this work was the implementation of experimental design methodology in a compatibility study between ketoprofen (non-steroidal anti-inflammatory drug) and selected solid dosage forms excipients. The fractional factorial design was used to generate a matrix of multi-component mixtures of ketoprofen and selected excipients. In order to accelerate any chemical incompatibilities, the received mixtures were exposed to elevated temperature and humidity (60°C/75% RH) in a climate chamber for 3 weeks. The ketoprofen-excipients compatibility was studied by means of the RP-HPLC method. It was confirmed that the type of disintegrant had a strong impact on ketoprofen degradation. The incompatibility in mixtures of ketoprofen with sodium starch glycolate was indicated. According to literature data, it may be the result of a decrease in crystallinity and thus a decrease in the stability of ketoprofen in the presence of sodium starch glycolate. The effects of the other types of excipients were statistically insignificant (p > 0.05). The applied experimental design methodology allowed for a rational selection of optimal excipients and thus, this approach may support significantly decision-making in the pharmaceutical industry.

A good understanding of the physicochemical characteristics of a drug substance and excipients is necessary to obtain a safe and effective drug dosage form. Based on the current recommendations of the regulatory agencies (European Medicines Agency, US Food and Drug Administration) regarding the implementation of the Quality by Design concept at the drug product development stage, this research work is focused on the application of an experimental design approach in preformulation studies. The purpose of this research work was the implementation of experimental design methodology in a compatibility study between ketoprofen (non-steroidal anti-inflammatory drug) and selected excipients in solid dosage forms. The fractional factorial design was used to generate a matrix of eight multi-component mixtures of ketoprofen and selected excipients. Four different excipients (binders, disintegrants, fillers, and glidants) were used as independent variables. To accelerate any chemical incompatibilities, the received mixtures were exposed to elevated temperature and humidity (60°C/75% RH) in a climate chamber for three weeks. The compatibility of ketoprofen with different excipients was studied by means of the RP-HPLC method. This chromatographic technique allowed for a determination of the loss in ketoprofen content after the exposition of multi-component mixtures to elevated temperature and humidity. It was confirmed that the type of disintegrant had a strong statistical impact on ketoprofen degradation (p < 0.05). The results revealed an incompatibility in mixtures of ketoprofen with sodium starch glycolate. According to the literature data, this may be the result of a decrease in crystallinity and thus a decrease in the stability of ketoprofen in the presence of sodium starch glycolate. The effects of the other types of excipients were statistically insignificant (p > 0.05). The applied experimental design methodology allowed for the rational selection of optimal excipients and thus, this approach may significantly support decision-making in the pharmaceutical industry. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to develop evaluation methods for multicomponent system interactions between drug excipients of three active pharmaceutical ingredients, namely, monoammonium glycyrrhizinate (MAG), glycine (Gly) and DL-methionine (Met), by using thermal and non-thermal techniques. Methods: Simultaneous thermal (TGA/DTG-DSC) analytical techniques, isothermal stress testing-high-performance liquid chromatography (IST-HPLC), scanning electron microscopy (SEM), and X-ray powder diffraction (XRPD) were used to investigate the characterization and potential physical and chemical interactions. Results: Based on the TGA/DTG-DSC results, the three drugs could maintain thermal stability at temperatures below 150 °C and were compatible with microcrystalline cellulose (MCC), calcium carboxymethylcellulose (CC), hydroxypropyl methyl cellulose (HPMC), low-substituted hydroxypropyl cellulose (L-HPC), magnesium stearate (MS), and poly(vinylpyrrolidone) (PVP). MAG, Gly and Met had physicochemical incompatibilities with lactose monohydrate (LM) based on thermal investigations, which was confirmed using IST-HPLC experiments. XRPD analysis indicated that crystalline transformation did not occur among all drug-excipient mixtures. Conclusion: TGA/DTG-DSC is a suitable and simple method for the detection of potential incompatibilities between drugs and excipients, especially for multicomponent formulations. These results can be used as a reference for the development of multicomponent glycyrrhizin (GL) solid dosage forms. [ABSTRACT FROM AUTHOR]

The body of work described in this research paper evaluates the compatibility between Fenbendazole (Fen), which is a broad-spectrum anthelmintic with promising antitumor activity, and three polymeric excipients commonly applied in pharmaceutical dosage forms. The assessment of binary mixtures was performed by differential scanning calorimetry and thermogravimetric analysis/derivative thermogravimetry to predict physical and/or chemical interactions, followed by X-ray diffraction spectroscopy (XRD), Fourier transform infrared spectroscopy (FTIR), and high-performance liquid chromatography (HPLC) to confirm or exclude any interactions. Thermal studies suggested the presence of interactions between Fen and P 407, PCL, and PLA. To validate these data, XRD showed that Fen is compatible with PCL and PLA, suggesting some interaction with P 407. FTIR demonstrated that PCL and PLA can establish physical interactions with Fen; moreover, it suggested that P 407 interacts not only physically but also chemically, which was later proved by HPLC to be only new intermolecular interactions. This work supports the further application of P 407, PCL, and PLA for the development of new medicinal and veterinary formulations containing Fen, since they do not affect the physical and chemical characteristics of the active ingredient and consequently its bioavailability and therapeutic efficacy.

In this paper, ten samples containing promestriene (PRMS) were investigated, namely the pure active pharmaceutical ingredient (API) and nine binary mixtures prepared with commonly used excipients in solid pharmaceutical formulations. The necessity of such study is represented by the fact that the physicochemical screening of PRMS is not reported in the literature. Also, as convergent arguments for the necessity of this study, it can be mentioned that on Romanian pharmaceutical market, promestriene containing formulations are no longer commercialized since 2015, creating health problems to a large category of patients. As such, this study can serve as a starting point for the adequate selection of ingredients used in magistral preparations, with increased stability and bioavailability. The study revealed that PRMS is compatible with all of the selected excipients, namely methyl 2-hydroxyethyl cellulose (tylose), methyl cellulose (MethocelTM), starch, mannitol, magnesium stearate, magnesium citrate, Talc, colloidal SiO2 (aerosil) and polyvinylpyrrolidone K-30 (PVPK30), as confirmed by universal attenuated total reflectance Fourier transform infrared (UATR-FTIR) spectroscopy, powder X-ray diffraction patterns and thermal analysis. [ABSTRACT FROM AUTHOR]

Fenbendazole (fen) or methyl N-(6-phenylsulfanyl-1H-benzimidazol-2-yl)carbamate is a broad-spectrum anthelmintic from the class of organic compounds known as benzimidazoles. Despite its pharmacological potential, fen has a limited application in oral pharmaceutical dosage forms due to its low aqueous solubility leading to an unsatisfactory bioavailability. This work aims to evaluate the compatibility between fen and poly(ethylene oxide) (PEO) applying differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR), followed by the processing of solid dispersions using hot-melt extrusion (HME) with thermal evaluation by DSC, drug dispersion assessment by scanning electron microscopy (SEM) with electron-dispersive X-ray spectroscopy (EDX), and drug release profile by ultraviolet–visible spectroscopy (UV–Vis). The results obtained from the compatibility study using thermal and non-thermal techniques proved that fen and PEO are compatible. The thermal analysis of solid dispersions showed that the extrusion process increases the polymer's crystalline content when compared to powder mixtures. It also demonstrated that PEO dissolves fen crystalline structure, thus converting it to an amorphous state. SEM with EDX showed that solid dispersions had a homogeneous distribution of fen in the polymeric matrix with the presence of voids, pores, and ducts. Dissolution testing proved that solid dispersions of fen 5% and PEO 95% processed at 50 rpm was able to improve significantly the drug solubility in water-based media. Thus, this work brings a new solution to improving the poor-water solubility of fen using PEO to develop solid dispersion formulations processed by HME. [ABSTRACT FROM AUTHOR]

The interactions between active pharmaceutical ingredients (APIs) and excipients may lead to API degradation, thereby affecting the safety and efficacy of drug products. Cbf-14 is a synthetic peptide derived from Cathelicidin-BF, showing potential for bacterial and fungal infections. In order to assess impurities in Cbf-14 gel, we developed a two-dimensional liquid chromatography coupled with quadrupole/time-of-flight mass spectrometric method. A total of eleven peptide degradation impurities were identified and characterized. Furthermore, the compatibility tests were conducted to evaluate the interactions of Cbf-14 with glycerol and methylcellulose, respectively. The results revealed that the impurities originated from condensation reactions between Cbf-14 and aldehydes caused by glycerol degradation. Several aldehydes were employed to validate this hypothesis. The formation mechanisms were elucidated as Maillard reactions between primary amino groups of Cbf-14 and aldehydes derived from glycerol degradation. Additionally, the compatibility of Cbf-14 with glycerol from different sources and with varying storage times was investigated. Notably, the interaction products in the gel increased with extended storage time, even when fresh glycerol for injection was added. This study offers unique insights into the compatibility study of peptides and glycerol, contributing to the ongoing quality study of Cbf-14 gel. It also serves as a reference for the design of other peptide preparations and excipients selections.

The body of work described in this research paper evaluates the compatibility between Fenbendazole (Fen), which is a broad-spectrum anthelmintic with promising antitumor activity, and three polymeric excipients commonly applied in pharmaceutical dosage forms. The assessment of binary mixtures was performed by differential scanning calorimetry and thermogravimetric analysis/derivative thermogravimetry to predict physical and/or chemical interactions, followed by X-ray diffraction spectroscopy (XRD), Fourier transform infrared spectroscopy (FTIR), and high-performance liquid chromatography (HPLC) to confirm or exclude any interactions. Thermal studies suggested the presence of interactions between Fen and P 407, PCL, and PLA. To validate these data, XRD showed that Fen is compatible with PCL and PLA, suggesting some interaction with P 407. FTIR demonstrated that PCL and PLA can establish physical interactions with Fen; moreover, it suggested that P 407 interacts not only physically but also chemically, which was later proved by HPLC to be only new intermolecular interactions. This work supports the further application of P 407, PCL, and PLA for the development of new medicinal and veterinary formulations containing Fen, since they do not affect the physical and chemical characteristics of the active ingredient and consequently its bioavailability and therapeutic efficacy. [ABSTRACT FROM AUTHOR]

The assessment of reactive hazards and chemical incompatibilities is necessary for safe operations in the chemical and pharmaceutical industries. In this investigation, custom differential scanning calorimetry (DSC) high-pressure crucibles made of commonly used metals and alloys have been constructed in-house using a microwelding system containing a jewelry spot-welder and a microscope. They provide an inexpensive and efficient method to perform thermal hazard analysis and compatibility tests at elevated temperatures compared to a DSC with commercial high-pressure crucibles or an accelerating rate calorimeter (ARC). The application of these crucibles is demonstrated with case studies of the thermal hazard analysis of ammonium nitrate (AN) and an ionic liquid: 1-ethyl-3-methylimidazolium bis-(trifluoromethylsulfonyl)-imide ([emim]-[Tf2N]). [ABSTRACT FROM AUTHOR]

The aim of this work was to evaluate the compatibility between dipyrone, caffeine and orphenadrine citrate, active pharmaceutical ingredients (APIs) commonly used in fixed-dose combination (FDC) in analgesic medicines. The APIs were analyzed by Differential Scanning Calorimetry (DSC), Differential Thermal Analysis (DTA), Fourier Transform Infrared Spectroscopy (FTIR) and X-Ray Powder Diffraction (XRPD). DSC evaluated the heat and temperature of thermal events of APIs. Physical binary and ternary mixtures in the mass ratio of 1:1 and 1:1:1 were analyzed by DTA and showed only overlap of the peaks. DSC photovisual showed various phase transition processes with complete decomposition. FTIR and XRPD of binary and ternary mixtures showed no change in the profiles of APIs and the study showed that the APIs can be inserted in the same formulation.

Abstract The study is aimed to assess the compatibility of bilberry leaf powder extract (BLPE) with six excipients selected for sustained-release (SR) tablet formulation. The BLPE was obtained with the addition of L-arginine and Myo-inositol as the carriers. Thermogravimetric (TG-DTG) analysis and Fourier-transform infrared spectroscopy (FTIR), supported by Pearson correlation analysis, were applied to detect possible interactions in the binary mixtures (1:1) of the BLPE with each excipient. The TG-DTG showed some deviations in the thermal behavior of the BLPE / excipient mixtures. However, only the thermal behavior of magnesium stearate in the mixture significantly differed from individual samples, which suggested chemical interaction for this excipient. The FTIR analysis confirmed that the BLPE is compatible with Eudragit L100, Methocel K4M, Methocel K100LV, Avicel PH-101, and Plasdone S-630. Whereas it undergoes solid-state chemical interaction in the binary mixture with magnesium stearate. According to the FTIR-spectra, it is suggested that this interaction results in the formation of stearic acid and alkalization of the medium. These findings evidence for the possibility of using TG-DTG analysis as an independent thermal technique for compatibility studies and also confirm the earlier reported interaction of basic lubricants, e.g., stearic salts, with active ingredients containing amino groups.

Background: The SARS-CoV-2 pandemic has resulted in a dramatic rise of the demand for medical devices and drugs. In this context, an important shortage of programmable syringe pumps, used to administrate different drugs in intensive care units, was seen. The opportunity of administrating combinations of five intensive care units selected drugs (Sufentanil, Clonidine, Loxapine, Midazolam, and Ketamine) was considered. Methods: The drug mixtures were studied in a pure form or diluted in NaCl 0.9% or G5%. Twenty-six possible combinations of the five drugs were produced in glass vials or polypropylene syringes and stored at 25 °C for 14 days. The LC method was implemented to study drugs combinations in the presence of the degradation products. The clearness and pH were also monitored. Results: All the 26 possible combinations displayed adequate physicochemical stability at 25 °C: at least 3 days and 7 days, respectively, for the dilution in 0.9% NaCl or glucose 5%, and the pure drug products mixtures. Conclusions: The study provided sufficient stability results, covering the medication administration period of at least three days. The combination of more than two drugs offers the advantage of minimizing the individual doses and reduces unwanted side-effects. Hence, this study opens up the possibility of combining the five drugs in one single syringe, which is useful especially under the current circumstances associated with an important shortage of programmable syringe pumps and pharmaceuticals. [ABSTRACT FROM AUTHOR]

Spironolactone is a potassium-sparing diuretic used as treatment for several diseases such as bronchopulmonary dysplasia, precocious puberty, hypertension or primary aldosteronism in child population. Because of the lack of paediatric formulations in the market, two types of solid oral formulation containing 2.5 and 10 mg of spironolactone were developed. During stability studies, excessive degradation was observed. As presented in this work, the degradation of spironolactone was linked to a drug excipient interaction between spironolactone and magnesium stearate via alkaline hydrolysis degradation pathway. In order to help the re-formulation with another lubricant, a complete drug excipient compatibility study was performed using thermal analysis techniques associated with chromatographic quantification of the drug after an isothermal stress testing. Spironolactone presents physicochemical incompatibilities with sodium benzoate, sodium stearyl fumarate, PEG 8000, PEG 20,000 and stearic acid. But no degradation was observed with PEG 20,000 and stearic acid indicating chemical compatibility. In total, talc, stearic acid and PEG 20,000 could be used for re-formulation of spironolactone paediatric drug. [ABSTRACT FROM AUTHOR]

Aripiprazole (ARP) is one of the newest antipsychotic drugs, exhibiting very low aqueous solubility and high lipophilicity. Considering the necessity of improvement of ARP physicochemical properties and its biopharmaceutical profile, cyclodextrin complexation of the drug substance was performed. As selected cyclodextrin, a functionalized β-cyclodextrin was used, namely heptakis(2,6-di-O-methyl)-β-cyclodextrin (DIMEB), and the supramolecular adduct ARP/DIMEB was prepared by kneading technique and characterized using thermoanalytical tools (TG—thermogravimetry/DTG—derivative thermogravimetry/HF—heat flow), powder X-ray diffractometry patterns (PXRD), universal-attenuated total reflectance Fourier transform infrared (UATR-FTIR) and UV (ultraviolet) spectroscopy and, as well, saturation solubility studies. Job's method was used for the stoichiometry of APR/DIMEB inclusion complex determination, which was found to be 1:2. Molecular modeling studies were complementary realized as to get a view over the way that ARP is hosted inside the cyclodextrin. The compatibility between the inclusion complex and some common pharmaceutical excipients, namely starch, magnesium stearate, lactose monohydrate, microcrystalline cellulose and methylcellulose, has been evaluated by means of thermal methods of analysis (TG/DTG/HF), UATR-FTIR spectroscopy and PXRD pattern. The preformulation data regarding the compatibility of ARP/DIMEB complex with selected excipients suggested that under ambient conditions, chemical interactions are observed solely between ARP/DIMEB inclusion complex and magnesium stearate, as indicated by the UATR-FTIR spectroscopy. The incompatibility in the system ARP/DIMEB + MgS is also confirmed by the PXRD study, this second investigational technique revealing also the advanced amorphization of components during mixing of complex with starch, microcrystalline cellulose and methylcellulose, but without indicating interactions. Later on, under thermal stress, thermally induced interactions occur between the components in the systems containing magnesium stearate and methylcellulose, while starch, microcrystalline cellulose and lactose can be safely used as excipients in developing solid formulations containing ARP/DIMEB inclusion complex as active pharmaceutical ingredient. [ABSTRACT FROM AUTHOR]

A drug–drug and drug–excipient interactions and compatibilities study was conducted for two fixed-dose combination (FDC) products containing olmesartan medoxomil (OLM)/hydrochlorothiazide (HCT) 20/12.5 mg and OLM/HCT 40/12.5 mg during their development including storage. The study consisted of the evaluation of samples retrieved during all stages of a real manufacturing process. Powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), thermogravimetry (TGA), Fourier transform infrared spectroscopy (FT-IR), and contact angle techniques were applied to the samples to determine interactions and incompatibilities. Dissolution tests and long-term stability studies were conducted to evaluate dosage form performance. Results showed weak solid–state interactions able to obtain a eutectic mixture of OLM and HCT while microcrystalline cellulose (MC) impacted the thermal stability of both drugs. Reliable dissolution and long-term stability tests confirmed that the interactions observed were not considered incompatibilities because they were not influenced by the performance of the final products.

Background: The SARS-CoV-2 pandemic has resulted in a dramatic rise of the demand for medical devices and drugs. In this context, an important shortage of programmable syringe pumps, used to administrate different drugs in intensive care units, was seen. The opportunity of administrating combinations of five intensive care units selected drugs (Sufentanil, Clonidine, Loxapine, Midazolam, and Ketamine) was considered. Methods: The drug mixtures were studied in a pure form or diluted in NaCl 0.9% or G5%. Twenty-six possible combinations of the five drugs were produced in glass vials or polypropylene syringes and stored at 25 °C for 14 days. The LC method was implemented to study drugs combinations in the presence of the degradation products. The clearness and pH were also monitored. Results: All the 26 possible combinations displayed adequate physicochemical stability at 25 °C: at least 3 days and 7 days, respectively, for the dilution in 0.9% NaCl or glucose 5%, and the pure drug products mixtures. Conclusions: The study provided sufficient stability results, covering the medication administration period of at least three days. The combination of more than two drugs offers the advantage of minimizing the individual doses and reduces unwanted side-effects. Hence, this study opens up the possibility of combining the five drugs in one single syringe, which is useful especially under the current circumstances associated with an important shortage of programmable syringe pumps and pharmaceuticals.

Hydroxychloroquine is effectively used in the treatment for malaria, lupus erythematosus and rheumatoid arthritis. The study of drug–excipient compatibility is an important tool for the development of safe and effective pharmaceutical forms. The present study describes the use of thermal and nonthermal techniques for evaluating the physicochemical compatibility of hydroxychloroquine with excipients for the development of solid dosage forms, including microcrystalline cellulose, corn starch, mannitol, magnesium stearate and colloidal silicon dioxide. The analytical techniques employed to evaluate the drug and the drug–excipient interactions in solid binary mixtures (1:1 w:w) were differential scanning calorimetry (DSC), thermogravimetry, Fourier transform infrared spectroscopy (FTIR) and isothermal stress test. Four different formulations were prepared and drug dissolution test was determined by rotating-basket system method in water. Evidence of solid-state interactions of hydroxychloroquine and mannitol, magnesium stearate and colloidal silicon dioxide was observed in the DSC analysis and subsequently confirmed by FTIR; however, no degradation profile was observed by HPLC and no interference was seen in the drug dissolution rate and no change in physicochemical properties of hydroxychloroquine was observed. The combination of techniques is very important to correctly identify drug–excipients incompatibilities in the earliest stage of a formulation design in order to ensure the choice of suitable excipients for the development of stable and effective dosage forms of hydroxychloroquine. [ABSTRACT FROM AUTHOR]

The present research work is based on the formulation and evaluation of topical gel of Ibuprofen where Carbopol 940 is used as the polymer. Gels were prepared by dispersing the polymers in a mixture of water and glycerol with methyl paraben as the preservative and the varying amount of ibuprofen, being kept under magnetic stirring until the homogeneous dispersion was formed. The dispersion was then neutralized and made viscous by the addition of triethanolamine. The Carbopol gels of Ibuprofen were found to be homogenous with good drug loading. The pH of all the gel formulations was found within the neutral pH range which is compatible with skin. And the viscosity of the formulations was found to be feasible for topical drug delivery. The drug content of the three formulations was found in the range of 87.56% to 90.45% which shows efficient drug loading. Results of In vitro drug release study showed that F5 formulation has better diffusion of drug through egg membrane and hence further permeation studies were carried out through rat epidermis. The compatibility study showed that the major peaks in FTIR spectra of the pure drug were found to be intact in their physical mixture. Hence there is no interaction between drug and Carbopol in their physical mixture. Carbopol can be effectively used as the polymer for topical gel preparation. And F5 formulation containing 0.5 % w/w Carbopol 940 may be effectively used as topical transdermal delivery for Ibuprofen. [ABSTRACT FROM AUTHOR]

Thermal decomposition study of diammonium 5,5′-bistetrazole-1,1′-diolate (ABTOX) was investigated by using DSC. The result showed that ABTOX is less thermal sensitive than TKX-50. The kinetic parameters (E = 139.82 kJ mol−1 and lgA = 12.75 s−1) for thermal decomposition reaction of ABTOX were obtained. The compatibility of ABTOX with 1,3,5-trinitro-1,3,5-triazacyclohexane (RDX), 1,3,5,7-tetranitro-1,3,5,7-tetraazacyclooctane (HMX), 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaza-isowurtzitane (CL-20), 3-nitro-1,2,4-triazol-5-one (NTO), 1,1-diamino-2,2-dinitroethene (FOX-7), 2,6-diamino-3,5-dinitropyrazine-1-oxide (LLM-105), aluminum powder (Al), Estane-TPU-5702 and two kinds of fluoropolymers (F-2311 and F-2603) were evaluated by using DSC. The results showed that CL-20/ABTOX, FOX-7/ABTOX and F-2603/ABTOX were exhibiting good compatibility and RDX/ABTOX and Al/ABTOX had moderate compatibility. In addition, the compatibility of ABTOX with Estane-TPU-5702 and F-2311 was not good. HMX/ABTOX, NTO/ABTOX and LLM-105/ABTOX had poor compatibility. Furthermore, the self-accelerating decomposition temperature was calculated to be 152 °C and 150 °C in commercial wooden and PE cylinder, respectively. [ABSTRACT FROM AUTHOR]

The aim of this study was to characterize the interaction between the binary systems of albendazole (ABZ)—cyclodextrins (CDs) with pharmaceutical excipients. Hydroxyl-propyl-beta-cyclodextrin (HPBCD) and random methyl-beta-cyclodextrin (RAMEB) were used as cyclodextrins and magnesium stearate, mannitol, polyvinylpyrrolidone K30 (PVP K30), colloidal silica, starch, and talc were used as excipients. The utilized investigation techniques were attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), powder X-ray diffractometry (PXRD) and thermoanalytical techniques: thermogravimetry (TG)/derivative thermogravimetry (DTG)/heat flow (HF) and differential scanning calorimetry (DSC). The ATR-FTIR analysis clearly suggested interactions under ambient conditions between ABZ-HPBCD with PVP K30 and SiO2 and between ABZ-RAMEB with SiO2 and talc. The PXRD patterns indicated the formation of less crystalline mixtures but with no clear indication of interactions, since no peaks appeared nor disappeared. The modifications on the DSC curves suggested an interaction between ABZ-HPBCD and PVP K30 and SiO2 respectively, and in case of ABZ-RAMEB was observed an interaction with talc. Thermal analysis (TG/DTG/HF) carried out in open crucibles in dynamic air atmosphere suggested that at temperatures over 40 °C dehydration of samples occurred, later followed by thermolysis and appearance of interactions in all studied cases. Our study concludes by recommending precautionary measures in elaborating new solid formulations containing ABZ, HPBCD and PVP K30/SiO2 and for the ones containing ABZ, RAMEB and Talc/SiO2, due to the present interactions under ambient conditions. [ABSTRACT FROM AUTHOR]

This paper deals with the study of compatibility between antihyperlipidemic agent atorvastatin calcium trihydrate (ATV) and eight pharmaceutical excipients used in the development of solid dosage forms, namely citric acid, anhydrous lactose, magnesium citrate, magnesium carbonate, sodium carboxymethyl cellulose, polyvinylpyrrolidone K30, colloidal silica and sorbitol. As investigational tools, universal attenuated total reflectance Fourier transform infrared spectroscopy and powder X-ray diffractogram patterns were used for binary mixtures of ATV with each excipient at ambient condition and then completed by subjecting the samples to thermal stress using thermal analysis (TG/DTG/HF), in non-isothermal conditions and in oxidative medium. It was shown the binary mixtures do not present interactions between ATV and excipients when stored under ambient conditions for 2 months, while under thermal stress, ATV presents interactions with sorbitol. [ABSTRACT FROM AUTHOR]

Monoglycerides (MGs) such as glycerol monolaurate (GML) and glycerol monostearate (GMS) have been used as excipients in oral formulations because of their emulsifying effect as well as their ability to inhibit the precipitation and intestinal efflux of drugs. Excipient-drug compatibility studies, however, have been underexplored. In this study, benznidazole (BNZ) was selected as a drug model due to the difficulty in improving its solubility and because of the potential impact on public health (it is the only drug currently used to treat Chagas disease). The effect of different processing conditions (maceration, ball milling, and melting) on the physical-chemistry properties of BNZ/MGs mixtures was investigated to guide the rational development of new solid formulations. GML was more effective in improving the solubility of BNZ, which could be due to its more malleable structure, less hydrophobic nature, and greater interaction with BNZ. The formation of hydrogen bonds between the imidazole group of BNZ and the polar region of GML was confirmed by spectroscopy analyses (IR, 1H NMR). The higher the monoglyceride content in the mixture, the higher the BNZ solubility. Regardless of the method of processing the mixture, the drug was found to be crystalline. Polarized light microscopy analysis showed the presence of spherulites. Overall, these findings suggest that preparation methods of BNZ:MGs formulations that involve thermal or/and mechanical treatment have a low impact on the solid properties of the material, and this allows for the production of formulations with reproducible performance. [Display omitted] • Monoglycerides represent an alternative for improving lipophilic drug solubility. • The imidazole group of BNZ and the polar region of MG interact via a hydrogen bond. • Melting, maceration, and ball milling did not affect the crystallinity of BNZ after being mixed with monoglycerides. • No improvement in the powder characteristics was found by using high-energy methods. [ABSTRACT FROM AUTHOR]

Entacapone, a selective and reversible inhibitor of catechol-O-methyltransferase, is used in the treatment of Parkinson’s disease in combination with levodopa/carbidopa to treat the symptoms of end-of-dose “wearing-off” effect. Considering that new formulations are researched constantly, proper knowledge of the active pharmaceutical ingredients is crucial in the preformulation stages. Kinetic analysis was performed using three methods: one integral—Flynn-Wall-Ozawa method, one differential—Friedman method, and modified nonparametric kinetics method (NPK). The thermoanalytical curves were registered at five different heating rates: β = 5, 7, 10, 12, and 15 °C min−1. Analysis was conducted in the dynamic air atmosphere to highlight potential thermooxidative processes. This paper deals with the investigation of solid-state stability and compatibility of binary mixture of entacapone with various pharmaceutical excipients by two instrumental techniques, such as universal attenuated total reflection Fourier transform infrared and thermal analysis (TG/DTG/HF). The excipients used in the mixture were: mannitol, silicon dioxide, talc, sorbitol, magnesium stearate, and povidone. [ABSTRACT FROM AUTHOR]

It is essential to guarantee physico-chemical compatibility between the active pharmaceutical ingredient (API) and the components that are planned to be used in the development of a pharmaceutical formulation. A successful compatibility study allows distinguishing between the excipients that can be used and those that may represent a risk in the quality, safety and efficacy of the medication. The present study focuses on the identification of possible incompatibilities between Rupatadine fumarate and the excipients of three formulation prototypes for the development of API´s 10 mg tablets. Samples of each raw material, placebos and preformulation mixtures were analyzed by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), X-ray diffraction (XDR) and infrared spectroscopy (IRS). The results obtained were analyzed and contrasted with the literature. Based on these, it is demonstrated that the excipients used along with the API do not generate problems in terms of compatibility, as there are no chemical changes in the drug. [ABSTRACT FROM AUTHOR]

Most of the pharmaceutical products are formulated as solid dosage form, which may present drug–excipient interactions that lead to changes in the chemical nature of the drug, such as solubility and bioavailability and may compromise its safety and effectiveness. Differential scanning calorimetry (DSC) is a widely used method for the rapid evaluation of the drug-excipient compatibility and the stability of the mixture formed; however, there is no consensus on the preparation methods of the drug–excipient mixtures. The aim of this study was to investigate the influence of the mixing method on the drug–excipient compatibility studies by means of DSC analysis, using tenofovir disoproxil fumarate as a drug model. Statistical analysis revealed significant differences in the heat of fusion of the drug in the mixtures prepared by several mixing methods. Vortex Mixer with a Pop-Off Cup used for 3 min proved to be very satisfactory for these studies. A polymorphic transition was observed in the mixture prepared with the mortar and pestle. Therefore, this method should be avoided since it may induce errors in the interpretation of DSC results. In this way, the mixing method used to prepare a mixture for studies of interactions between the API and the excipients in a pharmaceutical formulation has a great influence on the results and it must be chosen carefully. [ABSTRACT FROM AUTHOR]

Mycophenolate mofetil is used as an immunosuppressive agent to prevent acute rejection of transplanted organs. Mycophenolate mofetil is rapidly absorbed following oral administration and hydrolysed by esterases in the liver and kidney to its active metabolite, mycophenolic acid, a selective and reversible inhibitor of inosine monophosphate dehydrogenase. Due to the clinical advantages of mycophenolate mofetil, there has been an increase in the number of mycophenolate mofetil formulations in the market in recent years. This study aims to investigate the compatibility of mycophenolate mofetil with several excipients frequently used in drug formulations, hence a robust analysis of thermal-induced events on the pharmaceutical active agent and its binary mixtures. To evaluate the thermal behaviour of mycophenolate mofetil-excipient mixtures, TG-DSC curves were recorded from 40 to 500 °C in dynamic air flow. The study was also conducted in nitrogen atmosphere by DSC analysis, using a temperature programme from 40 to 350 °C. Compatibility studies performed by TG-DSC analysis showed some peak shifts in the TG curve and DSC curve, hence a supposition that interactions could occur. The DSC curve recorded for the same mixture does not behave as a sum of the DSC curves of the pure compounds. This behaviour is put into the account of a thermally induced interaction between the pharmaceutical active agent and some of the excipients used in this study. [ABSTRACT FROM AUTHOR]

Nortriptyline (NRT), usually conditioned as hydrochloride, is a second-generation tricyclic antidepressant that is primarily used as a treatment option for major depression and chronic pain. In this study, a compatibility evaluation between an active pharmaceutical ingredient (API) and various excipients that form binary mixtures is presented. As investigational methods, ATR-FTIR analysis and PXRD data were recorded for the binary mixtures under ambient conditions, and were later investigated by thermal analysis (TG-thermogravimetry/DTG-derivative thermogravimetry/HF-heat flow) in dynamic air atmosphere. Nortriptyline hydrochloride (NRT) was used as an active pharmaceutical ingredient, and binary mixtures with 13 excipients from different categories were formed (mass ratio 1:1), namely: microcrystalline cellulose (MC), calcium lactate (CaLact), stearic acid (StA), lactose monohydrate (Lact), polyvinylpyrrolidone K30 (PVP), magnesium stearate (MgSt), sodium carboxymethylcellulose (CMCNa), sorbitol (Sorb), mannitol (Man), gelatine (Gel), silica (SiO), starch (Starch), and talc (T). The PXDR patterns determined for the binary mixtures showed no incompatibility between the components since the diffraction profile consists in the superposing of the components' patterns, while the ATR-FTIR study indicated interactions in the discussed binary mixtures, suggesting that NRT is incompatible with PVP, Sorb, Man, StA, and Lact even under ambient conditions. Under thermal stress, interactions between NRT and excipients were observed at temperatures below the melting point of the API in the binary mixtures with PVP, Sorb, Man, StA, and Lact, while at high temperatures, all binary mixtures are thermally degraded due to thermolysis. [ABSTRACT FROM AUTHOR]

Extracts of medicinal plants are the starting point for the development of drugs and/or cosmetics obtained as plant active pharmaceutical ingredient. In the development of a pharmaceutical product is necessary the physical-chemical study of the formulation candidate, which will aim to provide possible incompatibilities between the active ingredients and excipients, which can affect the final product. This study was an important step in the development of sunscreen, because it identified, among other characteristics, problems related to the excipient, and the stability of the formulation. Thus, the aim of this work was to evaluate the compatibility study to develop a sunscreen using Schinopsis brasiliensis Engler extract as a preservative. The extract was obtained by spray dryer, and binary mixtures were produced with the excipients used in the production of a sunscreen, which were analyzed by differential scanning calorimetry with temperature range from 25 to 400 °C and heating rate of 10 °C min. In thermogravimetry the experiments were programmed at the temperature range from 25 to 900 using a heating rate of 10 °C min. Infrared and Fourier transform spectroscopy was recorded using KBr stressed disks in the range of 4000-500 cm. The results showed evidence of incompatibility between the extract and carboxymethylcellulose, hydroxyethyl cellulose, glycerin, sorbitol, sodium bicarbonate and calcium carbonate. With the results obtained were selected the excipients that weren't incompatible with the extract. Thus, the formulation was produced with Carbopol 940, propylene glycol, triethanolamine, octyl methoxycinnamate and S. brasiliensis Engler extract as preservative. [ABSTRACT FROM AUTHOR]

Purpose: Curcumin is a hydrophobic polyphenol isolated from dried rhizome of turmeric. Clinical usefulness of curcumin in the treatment of cancer is limited due to poor aqueous solubility, hydrolytic degradation, metabolism, and poor oral bioavailability. To overcome these limitations, we proposed to fabricate curcumin-piperine, curcumin-quercetin and curcumin-silibinin loaded polymeric nanoformulation. However, unfavourable combinations of drug-drug and drug-excipient may result in interaction and rises the safety concern. Hence, the present study was aimed to assess the interaction of curcumin with excipients used in nanoformulations. Methods: Isothermal stress testing method was used to assess the compatibility of drug-drug/drug-excipient. Results: The combination of curcumin-piperine, curcumin-quercetin, curcumin-silibinin and the combination of other excipients with curcumin, piperine, quercetin and silibinin have not shown any significant physical and chemical instability. Conclusion: The study concludes that the curcumin, piperine, quercetin and silibinin is compatible with each other and with other excipients.

Minimally invasive aesthetic and cosmetic procedures have increased in popularity. Injectable dermal fillers provide soft tissue augmentation, improve facial rejuvenation and wrinkles, and correct tissue defects. To investigate the use of adipose‑derived stem cells integrated with a hyaluronic acid based gel as a dermal filler, the present study used cytotoxicity studies, proliferation studies, adipogenic and osteogenic differentiation, apoptosis assays and scanning electron microscopy. Although hyaluronic acid induced low levels of apoptosis in adipose‑derived stem cells, its significantly promoted proliferation of adipose‑derived stem cells. Hyaluronic acid demonstrates little toxicity against adipose‑derived stem cells. Adipose‑derived stem cells were able to differentiate into adipocytes and osteoblasts. Furthermore, scanning electron microscopy revealed that adipose‑derived stem cells maintained intact structures on the surface of hyaluronic acid as well as in it, and demonstrated abundant cell attachments. The present study demonstrated the compatibility of adipose‑derived stem cells and hyaluronic acid based gels in vitro. [ABSTRACT FROM AUTHOR]

Donepezil (Don) is one of the main compounds used in the therapy of Alzheimer's disease. In this study, donepezil hydrochloride was investigated for solid-state compatibility with several pharmaceutical excipients like calcium lactate (CaL), mannitol (Man), magnesium stearate (MgSt), anhydrous lactose (LAnh), talc (T), magnesium citrate (MgC), sorbitol (Sb), silica (SiO), polyvinylpyrrolidone K30 (PVP), sodium carboxymethylcellulose (NaCMC) and starch (St) under ambient conditions, by ATR-FTIR spectroscopy and PXRD data, and later by thermoanalytical techniques (TG/DTG/HF), in order to evaluate the thermal-induced interactions. The instrumental investigations carried at ambiental temperature revealed no interaction between Don and selected excipients, while thermal treatment induced interactions between components in eight binary mixtures, except the ones containing magnesium citrate, talc and polyvinylpyrrolidone. [ABSTRACT FROM AUTHOR]

The aim of the present paper was the study of excipient-excipient interactions. It presents the compatibility study between two polymeric compounds used in pharmaceutical technology, namely carboxymethylcellulose and hydroxyethylcellulose, with other commonly used pharmaceutical excipients, such as polyvinylpyrrolidone, sorbitol, magnesium stearate, and talc. The compatibility investigations were carried out under ambient temperature and after decomposition by FTIR spectroscopy studies and later completed by the use of thermal analysis (TG/DTG/HF) data to study the influence of temperature over stability of binary mixtures. Carboxymethylcellulose and hydroxyethylcellulose present thermal-induced interactions with sorbitol and magnesium stearate. [ABSTRACT FROM AUTHOR]

Levodopa (L-Dopa or LD) is nowadays considered one of the essential medicines in the World Health Organization list, being a main treatment component for Parkinson's disease. This paper deals with the investigation of solid-state stability and compatibility of binary mixtures of Levodopa with various pharmaceutical excipients, by employment of several instrumental techniques, such as attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, powder X-ray diffraction (PXRD) data and thermal analysis (TG/DTG/HF). Along L-Dopa, eleven pharmaceutical excipients were investigated, namely calcium lactate (CaL), mannitol (Man), magnesium stearate (MgSt), anhydrous lactose (LAnh), talc (T), magnesium citrate (MgC), sorbitol (Sb), silica (SiO), polyvinylpyrrolidone K30 (PVP), sodium carboxymethylcellulose (NaCMC) and starch (St). FTIR analysis suggested possible interactions with calcium lactate, mannitol, magnesium stearate, anhydrous lactose, talc and SiO, which were confirmed by PXRD patterns, except for talc. When the samples were subjected to thermal stress, solely magnesium citrate did not present interactions in binary mixture, while all other excipients were incompatible with L-Dopa. [ABSTRACT FROM AUTHOR]

Compatibility between diazepam (DZP), a benzodiazepine drug used for the treatment of anxiety, and tablet excipients has been investigated by thermal analysis (differential scanning calorimetry-DSC and thermogravimetry-TG) and infrared (IR) spectroscopy. In order to investigate possible interactions, the components were prepared in 1:1 (w/w) mixtures. Moreover, individual samples as well as physical mixtures were stored in accelerated conditions at 40 °C/75 % RH for 3 months. Mixtures, which showed possible interactions, were also investigated in other ratios based on typical pharmaceutical solid formulation. DSC curves of DZP have shown an endothermic peak at 132 °C, which corresponds to the melting process in agreement with the literature. DSC curves of the mixtures containing DZP and colloidal silicon dioxide (CSD) indicated a possible interaction due to enthalpy values lower than expected. However, as this interaction was not confirmed by IR and TG, this suggests that these techniques are not sensitive enough to identify such interaction. These results suggest that there is a possible interaction, but not an incompatibility between DZP and CSD. For all other mixtures, it was not possible to identify significant interactions, suggesting that there are no compatibility issues. [ABSTRACT FROM AUTHOR]

Ferulic acid (4-hydroxy-3-methoxycinnamic acid) is a phytochemical constituent from the polyphenols group commonly found in whole grains, spinach, parsley, grapes and rhubarb. It has been widely applied in skin care formulations as photoprotective agent and delayer of cutaneous photoaging processes. This work aims to establish a protocol to the development of cosmetic formulations using thermoanalytical techniques (TG/DTG and DSC) and Pearson's correlation by FTIR data, in order to evaluate the compatibility between ferulic acid and excipients used in skin care formulations. The results obtained from the thermoanalytical techniques indicated compatibility between ferulic acid and the following excipients: passion fruit seed oil, Carbopol Ultrez 30, EDTA, Crodabase CR2, Crodamol™ GTCC and Dow Corning RM 2051. Nevertheless, the analysis also demonstrated the possibility of some interaction between ferulic acid and the following excipients: glyceryl stearate, Rapithix A-60 and Optiphen. To validate these results, it was demonstrated by Pearson's correlation that passion fruit seed oil, Carbopol Ultrez 30, EDTA, Crodabase CR2, Crodamol™ GTCC, Dow Corning RM 2051, glyceryl stearate and Rapithix A-60 do not have any incompatibility that may compromise ferulic acid properties. Finally, it was also proved a meaningful incompatibility between ferulic acid and Optiphen using Pearson's correlation. Thus, it is not recommended to use Optiphen in the development of cosmetic formulations to carry ferulic acid. [ABSTRACT FROM AUTHOR]

In this study, biodegradable poly(ε-caprolactone) (PCL) nanofibers (PCL-NF), collagen-coated PCL nanofibers (Col-c-PCL), and titanium dioxide-incorporated PCL (TiO-i-PCL) nanofibers were prepared by electrospinning technique to study the surface and structural compatibility of these scaffolds for skin tisuue engineering. Collagen coating over the PCL nanofibers was done by electrospinning process. Morphology of PCL nanofibers in electrospinning was investigated at different voltages and at different concentrations of PCL. The morphology, interaction between different materials, surface property, and presence of TiO were studied by scanning electron microscopy (SEM), Fourier transform IR spectroscopy (FTIR), contact angle measurement, energy dispersion X-ray spectroscopy (EDX), and X-ray photoelectron spectroscopy (XPS). MTT assay and cell adhesion study were done to check biocompatibilty of these scaffolds. SEM study confirmed the formation of nanofibers without beads. FTIR proved presence of collagen on PCL scaffold, and contact angle study showed increment of hydrophilicity of Col-c-PCL and TiO-i-PCL due to collagen coating and incorporation of TiO, respectively. EDX and XPS studies revealed distribution of entrapped TiO at molecular level. MTT assay and cell adhesion study using L929 fibroblast cell line proved viability of cells with attachment of fibroblasts over the scaffold. Thus, in a nutshell, we can conclude from the outcomes of our investigational works that such composite can be considered as a tissue engineered construct for skin wound healing. [ABSTRACT FROM AUTHOR]

The aims of this study were to develop a dry powder formulation from standardized extract of fruits of Physalis peruviana L., for oral administration, and to choose the best drying process for retaining the hypoglycemic activity, applying a factorial type experimental design. The development of a pharmaceutical formulation from an herbal extract has technological complications arising from inappropriate pharmaceutical characteristics related to its extract nature as a multicomponent system. P . peruviana extract showed the following technology difficulties: high hygroscopicity (which affects its flow, blend uniformity and stability), reduced flow properties (poor, non-uniform flow), high cohesivity, and low compressibility. To solve these problems, physical state changes of the extract (e.g. by absorption processes in a substrate) could contribute to improving its physical properties. The selection of excipients for use in the formulation was based on a compatibility study with binary solid mixtures (extract and each excipient) analyzed trough HPLC, and additionally, applying a factorial statistical experimental design to choose the best absorbent for the extract and the best drying method, evaluating like response variables: particle size, bulk and tap densities, angle of repose and hygroscopicity. Finally, a hypoglycemic assay was conducted in mice, using the best formulation. According to the compatibility study, the following excipients may be considered promising for use in a possible solid formulation from the ethanolic extract of fruits of P . peruviana: Disintegrants, absorbents and diluents: microcrystalline cellulose and corn starch; binder: polyvinylpyrrolidone. From the extract and the excipients selected as absorbents and binder (microcrystalline cellulose PH 101, 102, 200, corn starch and polyvinylpyrrolidone), different granules were produced, which were dried by two methods. The factorial experimental design showed that microcrystalline cellulose PH 102 and corn starch were the best absorbents, and that drying in a fluidized bed was the best method, offering advantages in terms of physicochemical properties such as particle size, density, voluminosity, flowability and hygroscopicity, compared to the initial extract and to the other formulations. The hypoglycemic assay showed that the activity of the extract remained after its transformation to a solid state. The results suggest that the dry powder formulation obtained from the ethanolic extract of fruits of P . peruviana may be of use as a future phytotherapeutic product, or a more stable intermediate herbal product than the extract, as an adjuvant in the treatment of diabetes. [ABSTRACT FROM AUTHOR]

This paper deals with the study of excipient-excipient interactions, rather than more commonly studied drug-excipient interactions. It presents the compatibility study between two polymeric compounds used in pharmaceutical technology, namely polyvinyl alcohol and polyvinylpyrrolidone, with other commonly used pharmaceutical excipients, like starch, mannitol, sorbitol, magnesium stearate and hydroxyethyl cellulose. The compatibility investigations were carried out under ambient temperature by FTIR spectroscopy studies and later completed by the use of thermal analysis (TG/DTG/HF) data to study the influence of temperature over stability of binary mixtures. [ABSTRACT FROM AUTHOR]

The aim of this study was to characterize atorvastatin and evaluate interactions between atorvastatin and various excipients by DSC and FTIR, using Pearson's correlation as a tool to corroborate possible interactions that it was not possible to evidence in visual analyses. The DSC curves were obtained using a Shimadzu calorimeter, Model DSC-60, in the aluminum crucible under heating rate of 20 °C min at a temperature of 25-400 °C. The spectra of the samples were obtained on a FTIR-ATR model IR prestige-21 Shimadzu spectrophotometer at a wavelength of 700-4000 cm on average of 20 scans. The theoretical spectrum was obtained using an ad hoc algorithm. From the analysis of DSC and evaluation of Pearson's correlation, it observed physical interactions with excipients: starch glycolate, pre-gelatinized starch, croscarmellose, sodium lauryl sulfate, magnesium stearate and mannitol. There is no interaction with lactose. Then, the Pearson's correlation was so important tool to evaluate possible interactions between IPAs and excipients, using FTIR data to corroborate DSC results. [ABSTRACT FROM AUTHOR]

Ziprasidone hydrochloride was fully characterized by Differential Scanning Calorimetry (DSC), Thermogravimetry (TG), Fourier Transform Infrared Spectroscopy (FT-IR), Powder X-ray Diffraction (PXRD) and Scanning Electron Microscopy (SEM). The stability study was carried out with 5 different pharmaceutical excipients (pregelatinized starch, magnesium stearate, microcrystalline cellulose, mannitol, polyvinylpyrrolidone - PVP). Binary mixtures of the drug-excipient were prepared in a 1:1(w/w) ratio and stored for 3 months in stability chamber (75% ± 5% of relative humidity and temperature of 40 °C ± 1 °C), then these samples were analyzed by High Performance Liquid Chromatography (HPLC) to evaluate the effect of each excipient on chemical stability and, consequently, on amount of drug in each sample. Data obtained by FT-IR and PXRD shown the polymorphic form F, corresponding to monohydrate ziprasidone hydrochloride. The thermal analysis demonstrated a mass loss of 4% until 100°C, corresponding to a water molecule. The following mass loss occurred from melting temperature (297°C) to 600°C, with total sample degradation. The HPLC results shown that, between 5 tested excipients, only magnesium stearate caused significant amount reduction of drug in the sample (amount found = 77% ± 3%). Then, the drug was compatible with pregelatinized starch, microcrystalline cellulose, mannitol and PVP; and incompatible with magnesium stearate, in these work conditions. [ABSTRACT FROM AUTHOR]

The importance of developing new pharmaceutical final formulations is nowadays well known. In this paper, we present the study of compatibility between bioactive antihyperlipidemic agent simvastatin and eight currently used pharmaceutical excipients for developing solid dosage forms, namely starch, microcrystalline cellulose, lactose monohydrate, polyvinylpyrrolidone, colloidal silica, talc, magnesium citrate and sorbitol. The compatibility investigations were carried out under ambient temperature by FTIR spectroscopy studies and PXRD patterns and then completed by the use of thermal analysis (TG/DTG/HF) data to study the influence of temperature over stability of binary mixtures. [ABSTRACT FROM AUTHOR]