Drug-Excipient Interactions of Seproxetine Maleate Hemi-Hydrate: Isothermal Stress Methods

Schildcrout, Sigmund A.; Risley, Donald S.; Kleemann, Rita L.

doi:10.3109/03639049309063006

Cited by 20 publications

(4 citation statements)

References 7 publications

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“…3f) showed the endothermic peak for the fluconazole melting point at 137.8°C. It was incompatible with the antidepressant seproxetine maleate [38] and with the bronchodilator clenbuterol [39]. Starch was compatible with the antihistaminic desloratadine [40] and with the atypical antipsychotic risperidone [41].…”

Section: Dsc Compatibility Studiesmentioning

confidence: 97%

Fluconazole–excipient compatibility studies as the first step in the development of a formulation candidate for biowaiver

Teleginski

Maciel

Mendes

et al. 2014

J Therm Anal Calorim

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The biowaiver of bioequivalence studies on class I drugs of the biopharmaceutics classification system (BCS) is aimed mainly at reducing the costs and the exposure of health volunteers to a new pharmaceutical formulation. Fluconazole is an important antifungal agent but in the literature it is not clear whether it belongs to BCS class I or III. Compatibility studies are considered to be the first step in product development and on considering a biowaiver candidate these gain even greater importance since the final product will not be submitted to in vivo tests. The aim of this study was to qualitatively determine the composition of a commercially available fluconazole formulation in the form of capsules with regard to the presence of critical excipients and to carry out compatibility studies by differential scanning calorimetry (DSC). One formulation did not contain sodium lauryl sulfate and contained mannitol, in contrast to the reference formulation, which could hinder the acceptance of the biowaiver. The interaction of fluconazole with microcrystalline cellulose and calcium hydrogen phosphate dihydrate was observed; however, no indication of incompatibility was found in the DSC analysis of the commercial pharmaceutical formulations. These interactions were also studied by Fourier transform infrared spectroscopy, where small changes in the bands were observed, and by X-ray Powder diffraction and scanning electron microscopy that did not evidence any modification in the solid state characteristics.

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Section: Dsc Compatibility Studiesmentioning

confidence: 97%

Fluconazole–excipient compatibility studies as the first step in the development of a formulation candidate for biowaiver

Teleginski

Maciel

Mendes

et al. 2014

J Therm Anal Calorim

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“…The tromethamine salt of ketorolac was found to partially convert to the 1-keto analogue and an amide on exposure to high humidity and temperature. 27 Schildcrout et al 28 reported 1,4-Michael adduct formation between seproxetine and maleic acid in a maleate salt, and Stahl 29 reported the covalent addition of a secondary amine to fumaric acid in a fumarate salt. Different counterions used in salt formation may also provide different microenvironmental pH values to a compound.…”

Section: Figure 8samountsmentioning

confidence: 98%

Selection of solid dosage form composition through drug–excipient compatibility testing

Serajuddin

Thakur

Ghoshal

et al. 1999

Journal of Pharmaceutical Sciences

172

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A drug-excipient compatibility screening model was developed by which potential stability problems due to interactions of drug substances with excipients in solid dosage forms can be predicted. The model involved storing drug-excipient blends with 20% added water in closed glass vials at 50 degrees C and analyzing them after 1 and 3 weeks for chemical and physical stability. The total weight of drug-excipient blend in a vial was usually kept at about 200 mg. The amount of drug substance in a blend was determined on the basis of the expected drug-to-excipient ratio in the final formulation. Potential roles of several key factors, such as the chemical nature of the excipient, drug-to-excipient ratio, moisture, microenvironmental pH of the drug-excipient mixture, temperature, and light, on dosage form stability could be identified by using the model. Certain physical changes, such as polymorphic conversion or change from crystalline to amorphous form, that could occur in drug-excipient mixtures were also studied. Selection of dosage form composition by using this model at the outset of a drug development program would lead to reduction of "surprise" problems during long-term stability testing of drug products.

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“…Talc, according to the European Pharmacopeia monograph, is defined only by its chemical composition as: Ba selected and pulverized native hydrous magnesium silicate with a chemical structure [Mg 3 Si 4 O 10 (OH) 2 ]^ [33]. It shows incompatibility with seproxetine maleate, as the interaction of seproxetine maleate with maleic acid in the presence of talc leads to the formation of an amide derivative [38]. Talc can exhibit color variation owing to the presence of iron and aluminum impurities.…”

Section: Lubricants Anti-adherents and Glidantsmentioning

confidence: 99%

Excipient Stability in Oral Solid Dosage Forms: A Review

et al. 2017

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The choice of excipients constitutes a major part of preformulation and formulation studies during the preparation of pharmaceutical dosage forms. The physical, mechanical, and chemical properties of excipients affect various formulation parameters, such as disintegration, dissolution, and shelf life, and significantly influence the final product. Therefore, several studies have been performed to evaluate the effect of drug-excipient interactions on the overall formulation. This article reviews the information available on the physical and chemical instabilities of excipients and their incompatibilities with the active pharmaceutical ingredient in solid oral dosage forms, during various drug-manufacturing processes. The impact of these interactions on the drug formulation process has been discussed in detail. Examples of various excipients used in solid oral dosage forms have been included to elaborate on different drug-excipient interactions.

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Drug-Excipient Interactions of Seproxetine Maleate Hemi-Hydrate: Isothermal Stress Methods

Cited by 20 publications

References 7 publications

Fluconazole–excipient compatibility studies as the first step in the development of a formulation candidate for biowaiver

Fluconazole–excipient compatibility studies as the first step in the development of a formulation candidate for biowaiver

Selection of solid dosage form composition through drug–excipient compatibility testing

Excipient Stability in Oral Solid Dosage Forms: A Review

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