Detecting Crystallinity in Amorphous Solid Dispersions Using Dissolution Testing: Considerations on Properties of Drug Substance, Drug Product, and Selection of Dissolution Media.

Autor:	Purohit HS; Development Sciences, Research and Development, AbbVie Inc., North Chicago, IL, USA., Zhang GGZ; Development Sciences, Research and Development, AbbVie Inc., North Chicago, IL, USA. Electronic address: geoff.gz.zhang@abbvie.com., Gao Y; Development Sciences, Research and Development, AbbVie Inc., North Chicago, IL, USA. Electronic address: gao.yi@abbvie.com.
Jazyk:	angličtina
Zdroj:	Journal of pharmaceutical sciences [J Pharm Sci] 2023 Jan; Vol. 112 (1), pp. 290-303. Date of Electronic Publication: 2022 Oct 25.
DOI:	10.1016/j.xphs.2022.10.020
Abstrakt:	Dissolution testing has long been used to monitor product quality. Its role in quality control of amorphous solid dispersion (ASD) formulations is relatively new. In the presence of the crystalline phase, the dissolution of ASDs is determined by the dynamics between the dissolution rate of the amorphous solids and the rate of crystal growth. The detection of crystalline phase by dissolution test has not been well understood in the context of drug properties, formulation characteristics and dissolution test variables. This study systematically evaluated the impact of key parameters such as intrinsic crystallization tendency of the API, drug loading, extent of dissolution sink conditions and level of crystallinity on the ASD dissolution behavior. The results indicated diverse dissolution behaviors due to the differences in the intrinsic crystallization propensity of the drug, the drug loading, the ASD polymers and the dissolution sink index. Each of the complex dissolution profiles were interpreted based on visual observations during dissolution, the appropriate sink index based on the amorphous solubility, and the competition between drug dissolution versus crystallization. The findings of this study provide insights towards the various considerations that should be taken into account towards rationally developing a discriminatory dissolution method. Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (Copyright © 2022 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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