Selection of solid dosage form composition through drugexcipient compatibility testing
Autor: | Serajuddin, Abu T. M., Thakur, Ajit B., Ghoshal, Rabin N., Fakes, Michael G., Ranadive, Sunanda A., Morris, Kenneth R., Varia, Sailesh A. |
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Zdroj: | Journal of Pharmaceutical Sciences; July 1999, Vol. 88 Issue: 7 p696-704, 9p |
Abstrakt: | A drugexcipient 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 drugexcipient blends with 20% added water in closed glass vials at 50 °C and analyzing them after 1 and 3 weeks for chemical and physical stability. The total weight of drugexcipient 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 drugexcipient 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 drugexcipient 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. |
Databáze: | Supplemental Index |
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