Effect of Moisture on Solid Dosage forms. can the Arrhenius Equation be used as a Predictor?

Carstensen, J.T.; Gerhardt, A.; Morris, Tommy C; Nikfar, F.

doi:10.3109/03639049009043799

Cited by 5 publications

(3 citation statements)

References 8 publications

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“…All salt forms except F-S-CAR decreased the hygroscopicity of the free base. The salts of mineral acids tend to be polar, leading to increased hygroscopicity . However, all three S-CAR salts of mineral acids in the current study presented low hygroscopicity.…”

Section: Resultscontrasting

confidence: 48%

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Preparation, Characterization, and Selection of Optimal Forms of (S)-Carvedilol Salts for the Development of Extended-Release Formulation

et al. 2021

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Metrics & MoreArticle RecommendationsABSTRACT: (S)-carvedilol (S-CAR) is the dominant pharmacodynamic conformation of carvedilol, but its further development for extended-release formulation is restricted by its poor solubility. This study aimed to prepare and screen S-CAR salts that could be used to improve solubility and allow extended release. Five salts of S-CAR with well-known acid counterions (i.e., phosphate, hydrochloride, sulfate, fumarate, and tartrate) were produced using similar processes. However, these salts were obtained with water contents of 1.60−12.28%, and their physicochemical properties differed. The melting points of phosphate, hydrochloride, and tartrate were 1.1−1.5 times higher than that of the free base. The solubility of S-CAR salts was promoted to approximately 3−32 times higher than that of the free base at pH 5.0−8.0. Typical pH-dependent solubilities were evidently observed in S-CAR salts, but considerable differences in solubility properties among these salts were observed. S-CAR phosphate and hydrochloride possessed high melting points, considerable solubility, and excellent chemical and crystallographic stabilities. Accordingly, S-CAR phosphate and hydrochloride were chosen for further pharmacokinetic experiments and pharmaceutical study. S-CAR phosphate and hydrochloride extended-release capsules were prepared using HPMC K15 as the matrix and presented extended release in in vitro and in vivo evaluations. Results implied that water molecules in the hydrated salt were a potential threat to the achievement of crystal stability and thermostability. S-CAR phosphate and hydrochloride are suitable for further development of the extended-release formulation.

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Section: Resultscontrasting

confidence: 48%

“…The salts of mineral acids tend to be polar, leading to increased hygroscopicity. 32 However, all three S-CAR salts of mineral acids in the current study presented low hygroscopicity. Besides, this finding did not agree with the hypothesis that the increase in the molecular size of the counter acid reduced the amount of lattice water.…”

Section: Resultscontrasting

confidence: 48%

Preparation, Characterization, and Selection of Optimal Forms of (S)-Carvedilol Salts for the Development of Extended-Release Formulation

et al. 2021

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“…Although purely solid-state degradation of drug substances is feasible, such instances are rare, and most drug degradation reactions in solid dosage forms involve moisture. 4,5 The presence of moisture is, therefore, essential in establishing the compatibility of drugs with excipients. Although the moisture may be incorporated in the system by exposing samples to high humidity, it has been our experience that the drugexcipient interaction at high humidity conditions always depends on the amount of free moisture present and on relative hygroscopicities of drug substances and/or excipients.…”

Section: Resultsmentioning

confidence: 99%

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

Serajuddin

Thakur

Ghoshal

et al. 1999

Journal of Pharmaceutical Sciences

173

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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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Effect of Small Levels of Impurities on the Water Vapor Sorption Behavior of Ranitidine HCl

2006

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It was concluded that small levels of degradants and/or impurities can drastically affect the moisture sorption profile of a deliquescent material, both through affecting the deliquescence relative humidity and by altering the overall interaction of the substance with moisture. Such changes in behavior may have significant effects on both active pharmaceutical ingredient and drug product stability during both processing and storage.

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Effect of Moisture on Solid Dosage forms. can the Arrhenius Equation be used as a Predictor?

Cited by 5 publications

References 8 publications

Preparation, Characterization, and Selection of Optimal Forms of (S)-Carvedilol Salts for the Development of Extended-Release Formulation

Preparation, Characterization, and Selection of Optimal Forms of (S)-Carvedilol Salts for the Development of Extended-Release Formulation

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

Effect of Small Levels of Impurities on the Water Vapor Sorption Behavior of Ranitidine HCl

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