Degradation Rate Observations as a Function of Drug Load in Solid-State Drug Products
| Autor: | Miroslav Suruzhon, Steven W. Baertschi, Allison L. Dill, Garry Scrivens, Timothy T. Kramer |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Drug
media_common.quotation_subject Kinetics Solid-state Pharmaceutical Science Thermodynamics Excipient 02 engineering and technology Activation energy 030226 pharmacology & pharmacy Excipients 03 medical and health sciences symbols.namesake 0302 clinical medicine Drug Stability medicine Degradation process media_common Arrhenius equation Chemistry Temperature Humidity 021001 nanoscience & nanotechnology Pharmaceutical Preparations symbols Degradation (geology) 0210 nano-technology medicine.drug |
| Zdroj: | Journal of pharmaceutical sciences. 108(5) |
| ISSN: | 1520-6017 |
| Popis: | Degradation rates of solid-state drug products generally increase as the drug load decreases. A model for quantifying this effect based on surface area ratios is proposed here. This model relates the degradation rate to an estimate of the proportion of drug substance in contact with the excipient, and that the drug substance in contact with excipients degrades more quickly. Degradation data from previously published case studies and from 5 new case studies were found to be consistent with our proposed model; our model performed better than similar previously published models. It was also found that the relationship between degradation rate and drug load is largely independent of the temperature and humidity conditions, suggesting that drug load solely affects the pre-exponential factor of the Arrhenius equation and does not significantly affect the activation energy of the degradation process. A second method for calculating the proportion of the drug substance surface in contact with the excipient surface is presented in the Supplementary Material. Fundamentally, the 2 methods are very similar and provide almost identical fits to the experimental data. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|