Characterization of venlafaxine hydrochloride and compatibility studies with pharmaceutical excipients

The thermal analytical study of venlafaxine hydrochloride, a third generation antidepressant, was investigated using thermogravimetry (TG) and differential scanning calorimetry (DSC). The DSC curves have shown a sharp endothermic event at 211 °C and TG demonstrated a single stage of mass loss between 254 and 283 °C. Solid-state characterization was carried out by DRIFT, SEM, and XRPD demonstrating the drug physicochemical properties including crystallinity. Drug-excipient compatibility studies investigated by DSC have shown a possible physical interaction of the drug with magnesium stearate, microcrystalline cellulose and starch. Nevertheless, these results where not confirmed by DRIFT and SEM analyses.     

Thermal compatibility studies of nitroimidazoles and excipients

Nitroimidazoles are heterocycle imidazoles with a nitrogen group incorporated in its structure. The objective of this study was to develop a model to characterize possible interactions between active substances and excipients using: Thermogravimetry, Differential Thermal Analysis, Differential Scanning Calorimetry, and DSC coupled to photovisual system. It was used three nitroimidazoles (metronidazole, secnidazole, and tinidazole) and two types of microcrystalline cellulose with different particle size (Microcel and Avicel). The binary mixtures were prepared in proportion (w/w) 1:1 (nitroimidazole:excipient). Thermogravimetric data demonstrated that the tinidazole was the nitroimidazole with better uniformity. The nitroimidazoles obeyed the zero order kinetic reaction, evidencing its vaporization processes. Differential thermal analysis data showed nitroimidazoles compatibility with the different microcrystalline celluloses studied, showing that microcrystalline celluloses stabilized the active substances. Calorimetric data of secnidazole showed two melting points, characteristic of the polymorphs presented in raw material. The vaporization constants values of nitroimidazoles studied were secnidazole > metronidazole > tinidazole and for the binary mixtures these values followed the order tinidazole > metronidazole ≥ secnidazole.     

Thermal characterization and compatibility studies of itraconazole and excipients for development of solid lipid nanoparticles

The current study was performed to investigate possible interactions between triazole antifungal drug itraconazole (ITR) with selected excipients commonly used for development of solid lipid nanoparticles. The excipients included common lipids (glyceryl behenate (Compritol 888 ATO?), glyceryl monostearate, stearic acid, and cetyl palmitate), charge inducers (dicetyl phosphate and stearlyamine), and surfactants (sodium cholate and sodium deoxycholate). Differential scanning calorimetry, isothermal stress testing, Fourier transform infrared spectral analysis, optical microcopy, and X-ray powder diffraction analysis were performed for assessing the compatibility between the drug and the excipients. Results of the study suggest that the stearic acid exhibited drug–excipient interactions, whereas all other excipients used in the study were found to be compatible with ITR.     

Pharmaceutical compatibility of dexamethasone with excipients commonly used in solid oral dosage forms

Dexamethasone is a glucocorticoid drug used for the treatment of acute and chronic inflammatory conditions, autoimmune diseases, some cancers, and several other pathologies. It is widely marketed worldwide especially under solid dosage forms. This study aimed to assess its compatibility with solid pharmaceutical excipients. Compatibility study was conducted through the preparation of binary mixtures (1:1, w/w) of dexamethasone with 12 selected excipients. Binary mixtures were analyzed by thermoanalytical techniques (thermogravimetric and differential thermal analysis), Fourier transform infrared spectroscopy, and X-ray diffraction. TG curves pointed only slight anticipations of dexamethasone decomposition. DTA curves showed interactions signs with microcrystalline cellulose 101 and 102, magnesium stearate, mannitol, and polyvinylpyrrolidone. Drug infrared absorption profile was not affected by the mixture with most excipients. X-ray diffractograms of all binary mixtures did not exhibit signs of interactions with changes of dexamethasone crystalline state. These results pointed that the interactions found by DTA technique were probably heat-induced. Therefore, the above-mentioned excipients should be carefully used in solid dosage forms with heat-based manufacturing processes.

     

Carvedilol: decomposition kinetics and compatibility with pharmaceutical excipients

Carvedilol (CARVE) is an important cardiovascular drug with limited bioavailability. To improve its therapeutic performance, the investigation of new dosage forms is of great interest due its relevance in clinical applications. Therefore, the aim of this work was to evaluate the stability of CARVE and its drug–excipient compatibility to support its pharmaceutical development. Kinetic analysis under isothermal conditions using thermogravimetry was performed to determine the activation energy of CARVE through an Arrhenius plot. Differential scanning calorimetry, Fourier transform infrared spectroscopy, and optical microscopy were used to test binary mixtures of CARVE and selected excipients. The activation energy of CARVE was 81.2 kJ mol^?1, and from the compatibility studies, all the excipients showed strong thermal interactions, presenting changes in the melting profile of the drug. In addition, analytical assays revealed no physical or chemical changes; because of this, all eight excipients studied are considered compatible and are recommended in formulations containing CARVE. All the evidence together attests to the low chemical reactivity of CARVE and provides useful information for the development of new pharmaceutical formulations containing CARVE.     

Compatibility study between chitosan and pharmaceutical excipients used in solid dosage forms

Microcrystalline cellulose is an excipient widely used in solid dosage forms as adsorbent, suspending agent, diluent, and disintegrant, depending on the percentage employed in the formulation. The structural similarity between cellulose and chitosan and the ecological advantage in the manufacturing process of chitosan have justified and reinforced the study of this polysaccharide as a novel pharmaceutical excipient. Nevertheless, it still does not appear to be present as constituent in any marketed medicine due to the absence of regulatory hurdles to standardize its physicochemical and functional specifications as well as its compatibility with other formulation ingredients. The physical compatibilities between chitosan and the most excipients used in solid dosage forms, such as diluents (microcrystalline cellulose, starch, lactose monohydrate, dicalcium phosphate dihydrate, and calcium carbonate), disintegrants (sodium starch glycolate, and croscarmellose sodium), and glidants (magnesium stearate, talc, sodium lauryl sulfate, and colloidal silicon dioxide), were studied by thermal analysis and FT-IR. In order to facilitate the IR spectra interpretations, an ad hoc algorithm was used to generate theoretical spectra to be compared with the respective experimental ones. Chitosan proved to be physically compatible with microcrystalline cellulose, starch, lactose, sodium starch glycolate, croscarmellose sodium, talc, colloidal silicon dioxide, and sodium lauryl sulfate. Moreover, chitosan raises the thermal stability of cellulose from 310 to 330 °C. Once the amino groups of chitosan were able to form coordination complexes with divalent cations of dicalcium phosphate dihydrate, calcium carbonate, and magnesium stearate, they were considered incompatible with chitosan.     

Compatibility study between sitagliptin and pharmaceutical excipients used in solid dosage forms

Differential scanning calorimetry (DSC) is a primary technique for measuring the thermal properties of materials, which reflects the physico-chemical properties of drug substances. In the present study, it is used as a screening technique for assessing the compatibility of sitagliptin with some currently employed pharmaceutical excipients. The influence of processing conditions and their effects (simple blending, co-grinding or kneading) on drug stability was evaluated. Sitagliptin showed a sharp endothermic peak at 212.1 °C with an enthalpy change of 131.5 J g^?1 indicating melting of drug. Facile transformation of dehydrated sitagliptin to monohydrate form was observed in some mixtures, disappearance of sharp melting endothermic peak of sitagliptin was observed in some mixtures. On the basis of DSC results, sitagliptin was found to be compatible with micro crystalline cellulose, croscarmellose, and pregelatinized starch. Some excipient interaction was observed with magnesium stearate, ascorbic acid, and citric acid. X-ray diffractometry and FT-IR were used as supportive tools in interpreting the DSC results. Overall, the excipients selected were compatible with the API and the mixtures are stable within the tested conditions. These results would be useful for formulation development of the film coated tablets of sitaglitptin.     

tudy on compatibility of imatinib mesylate with pharmaceutical excipients

Differential scanning calorimetry and thermogravimetric analysis with the support of X-ray powder diffraction and infrared spectroscopy were used as screening techniques for the compatibility testing of imatinib mesylate, with following excipients: magnesium stearate, polyvinylpyrrolidone, microcrystalline cellulose. In order to maximize the probability of interactions 1:1 (by mass) drug: excipient binary mixtures were analysed and compared to individual components. Additionally an influence of storage at temperatures of 25 and 40°C on physico-chemical stability on drug – excipient binary mixtures was investigated. The largest visible changes were observed in the DSC curves of imatinib mesylate – magnesium stearate mixtures.     

Compatibility studies between captopril and pharmaceutical excipients used in tablets formulations

Captopril (CAP) was the first commercially available angiotensine-converting enzyme (ACE) inhibitor. In the anti-hypertensive therapy is considered the selected drug has to be therapeutically effective together with reduced toxicity. CAP is an antihypertensive drug currently being administered in tablet form. In order to investigate the possible interactions between CAP and excipients in tablets formulations, differential scanning calorimetry (DSC) and thermogravimetric (TG) analysis completed by X-ray powder diffraction (XRPD) and Fourier transform infrared spectroscopy (FTIR) were used for compatibility studies. A possible drug-excipient interaction was observed with magnesium stearate by DSC technique.     

Physicochemical characterization and compatibility study of roflumilast with various pharmaceutical excipients

Journal of Thermal Analysis and Calorimetry - To rich flavor additive species of pyrazines, two new compounds of 3,6-dimethyl-2,5-pyrazinedicarboxylic acid 1-octen-3-yl ester (DMPOE) and...     

Thermal characterization of antimicrobial drug ornidazole and its compatibility in a solid pharmaceutical product

The ornidazole drug substance presents melt at approximately 90 °C (∆T = 85–98 °C), which is critical for its use on pharmaceutical manufacturing process. This work aimed the thermal characterization of ornidazole raw-material synthesized by three different manufacturers from India, China, and Italy, using the thermoanalytical techniques of DTA, DSC, and TG, besides the verification of its stability and compatibility as a solid pharmaceutical product by the analysis of its binary mixtures (BM) with excipients and a tablet formulation. The characterization includes the thermal decomposition kinetic investigation by Ozawa model using Arrhenius equation and drug purity determination by Van’t Hoff equation. The DSC purity determination and precision were compared with results from UV–Vis spectrophotometric and liquid chromatography, showing an adequate correlation before being recommended as a general method for purity assay. The drug raw-materials presented similar quality and zero-order kinetic behavior, besides showing differences on thermal stability. The drug presented compatibility with the tested excipients since the BM studied presented melting at the same temperature range as the drug and a decomposition temperature similar to the drug for two of the BM, and at a higher temperature for the others three of the BM evaluated, which presented excipients with higher molecular structure, capable of spatial coating on the small drug molecule promoting a physical interaction pharmaceutical acceptable. The tablet was processed by wet granulation and compressed under normal conditions of pressure and temperature, maintaining the physical properties of solid drug approving the manufacturing process used. In this study, the thermal analysis was used with success as an alternative method to characterize, quantify, and perform a preformulation study.     

Application of DSC and NIRS to study the compatibility of metronidazole with different pharmaceutical excipients

The purpose of the present work was to study the compatibility of metronidazole with different pharmaceutical excipients (hydroxypropyl methylcellulose, poly(ethylene oxide), microcrystalline cellulose, dicalcium phosphate dihydrate, and anhydrous dicalcium phosphate) using differential scanning calorimetry and diffuse reflectance spectroscopy. Dicalcium phosphate dihydrate was the only excipient that showed interaction with metronidazole even before storage. Changes referring to a possible transition to dihydrate form were observed in the thermal curves of anhydrous dicalcium phosphate after four weeks of storage. Although dicalcium phosphate dihydrate can be replaced by the anhydrous form in pharmaceutical formulations, the observed transition might negatively influence the stability of dosage forms.     

Evaluation of compatibility of itraconazole with excipients used to develop vesicular colloidal carriers

Liposomes and niosomes are known to be efficient vehicles for localized and systemic delivery of particularly lipophilic drugs resulting in their improved bioavailability, targeted delivery, and fewer side effects. These systems consist of bilayered membrane structures comprising amphiphilic molecules like phosphatidylcholine (liposomes) and nonionic surfactants (niosomes). Itraconazole (ITZ) is a widely used insoluble antifungal agent, which is known to be poorly absorbed from available marketed dosage forms. For countering the bioavailability related problem of oral ITZ products, vesicular systems like liposomes and niosomes could provide a rational approach. Drug–excipient interaction is being considered as an essential first step in development of any drug delivery system nowadays. Therefore, the present work describes the evaluation of drug–excipient interactions of ITZ with selected excipients used for development of liposomes and niosomes. Analytical techniques like differential scanning calorimetry, Fourier transform infrared spectroscopy, optical microcopy, and X-ray powder diffraction analysis were utilized for assessing the drug–excipient interactions. Isothermal stress testing was also performed to quantitatively measure the percent change in initial drug content from ITZ–excipient blends kept under stress conditions. The excipients included phospholipids (Phospholipon 90G^®, Phospholipon 90H^®), surfactants (Span 40 and Span 60), vesicular membrane stabilizer (cholesterol), and a solubilizer (3-hydroxypropyl-betacyclodextrin).     

Thermal analysis of prednicarbate and characterization of thermal decomposition product

In the present work, the thermal behavior of prednicarbate was studied using DSC and TG/DTG. The solid product remaining at the first decomposition step of the drug was isolated by TG, in air and N₂ atmospheres and was characterized using LC-MS/MS, NMR, and IR spectroscopy. It was found that the product at the first thermal decomposition step of prednicarbate corresponds to the elimination of the carbonate group bonding to C₁₇, and a consequent formation of double bond between C₁₇ and C₁₆. Structure elucidation of this degradation product by spectral data has been discussed in detail.     

Characterization and compatibility of dry extract from Annona muricata L. and pharmaceutical excipients

Journal of Thermal Analysis and Calorimetry - The aim of this study was to characterize and evaluate the compatibility of the dry extract (DE) of leaves of Annona muricata L. with pharmaceutical...     

Quantitative characterization and pharmaceutical compatibility between teneligliptin and widely used excipients by using thermal and liquid chromatography tandem mass spectrometry techniques

Journal of Thermal Analysis and Calorimetry - The aim of this work was to evaluate the quantitative characterization and pharmaceutical compatibility study of teneligliptin (TNG) with the commonly...     

Pharmaceutical approaches involving carvedilol characterization,compatibility with different excipients and kinetic studies

This study was performed to investigate the physical–chemical characteristics of carvedilol (CRV), complemented by compatibility studies with a great variety of pharmaceutical excipients. Thermogravimetry and differential scanning calorimetry, supported by diffuse reflectance infrared fourier transform spectroscopy (DRIFT), X-ray powder diffraction, and scanning electron microscopy (SEM) were selected as the solid-state techniques for the intended analyses. In addition, non-isothermal methods were employed to investigate kinetic data of CRV decomposition process under nitrogen and air atmospheres. CRV is characterized by an endothermic sharp event (T _peak = 389.81 K and ΔH _fusion of ?176.28 J g^?1) and a thermal decomposition behavior in two stages, totalizing 98 % of mass loss. The CRV pattern diffraction presents prominent peaks at 2θ: 5.92°, 14.90°, 18.62°, 24.47°, and 26.30°, and the DRIFT spectrum showed the main characteristics bands for CRV chemical functional groups. The SEM photomicrographs demonstrate that CRV is characterized by irregular blocky shaped crystals. Zero order kinetics was determined by Ozawa method in both nitrogen and air atmospheres. The compatibility results showed no evidence of any incompatibility among CRV and all the excipients analyzed.     

Thermal compatibility between hydroquinone and retinoic acid in pharmaceutical formulations

Thermogravimetry (TG) and differential scanning calorimetry (DSC) are used in pharmaceutical studies for characterization of drugs, purity, compatibility of formulations, identification of polymorphism, evaluation of stability, and thermal decomposition of drugs and pharmaceutical formulations. Hydroquinone (HQ) and products containing HQ have been widely used as depigmentation agents for lightening the skin. Retinoids are compounds that have the basic core structure of vitamin A and its oxidized metabolites, or synthetic compounds that share similar mechanisms of action as naturally occurring retinoids. Depigmentants and excipients were analyzed by TG and DSC. The dynamic thermogravimetric curves were obtained on a SHIMADZU thermobalance, model DTG-60, using an alumina crucible, at the heating rate of 10 °C min^?1, in the temperature range of 25–900 °C, under an atmosphere of nitrogen at 50 mL min^?1. The sample's mass was 10 ± 0.05 mg. The DSC curves were obtained using Shimadzu calorimeter, model DSC-60, using aluminum crucible, at the heating rate of 10 °C min^?1, in the temperature range of 25–400 °C. The thermogravimetric and calorimetric curves were analyzed using TASYS software SHIMADZU. In this study were found the interaction between retinoic acid (RA) and the following excipients: cetyl alcohol(CA), cetostearyl alcohol (CTA), glycerin(GLY), and dipropylene glycol (DPG), and that between HQ and the excipient, DPG. Therefore, additional studies are necessary to evaluate final formulations. Thermal analysis is an effective and reliable technique that can be used in the control of raw materials and pharmaceutical products, and for evaluating their employment potential in the development and characterization of products.