Degradation Rate Observations as a Function of Drug Load in Solid-State Drug Products.
| Autor: | Baertschi SW; Baertschi Consulting, LLC, Carmel, Indiana 46033., Dill AL; Eli Lilly and Company, Lilly Research Laboratories, Small Molecule Design and Development Indianapolis, Indiana 46285., Kramer TT; Eli Lilly and Company, Lilly Research Laboratories, Global Statistical Sciences Indianapolis, Indiana 46285., Scrivens G; Analytical Research and Development, Pfizer Inc., Sandwich, UK. Electronic address: garry.scrivens@pfizer.com., Suruzhon M; Analytical Research and Development, Pfizer Inc., Sandwich, UK. |
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| Jazyk: | angličtina |
| Zdroj: | Journal of pharmaceutical sciences [J Pharm Sci] 2019 May; Vol. 108 (5), pp. 1746-1755. Date of Electronic Publication: 2018 Dec 11. |
| DOI: | 10.1016/j.xphs.2018.12.003 |
| Abstrakt: | 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. (Copyright © 2019 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.) |
| Databáze: | MEDLINE |
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