20.500.12556/RUL-152194 Predictive potential of acido-basic properties, solubility and food on bioequivalence study outcome analysis of 128 studies Background and Objectives Risk assessment related to bioequivalence study outcome is critical for effective planning from the early stage of drug product development. The objective of this research was to evaluate the associations between solubility and acido-basic parameters of an active pharmaceutical ingredient (API), study conditions and bioequivalence outcome. Methods We retrospectively analyzed 128 bioequivalence studies of immediate-release products with 26 different APIs. Bioequivalence study conditions and acido-basic/solubility characteristics of APIs were collected and their predictive potential on the study outcome was assessed using a set of univariate statistical analyses. Results There was no difference in bioequivalence rate between fasting and fed conditions. The highest proportion of non-bioequivalent studies was for weak acids (10/19 cases, 53%) and neutral APIs (23/95 cases, 24%). Lower non-bioequivalence occurrence was observed for weak bases (1/15 cases, 7%) and amphoteric APIs (0/16 cases, 0%). The median dose numbers at pH 1.2 and pH 3 were higher and the most basic acid dissociation constant (pKa) was lower in the non-bioequivalent group of studies. Additionally, APIs with low calculated effective permeability (cPeff) or low calculated lipophilicity (clogP) had lower non-bioequivalence occurrence. Results of the subgroup analysis of studies under fasting conditions were similar as for the whole dataset. Conclusion Our results indicate that acido-basic properties of API should be considered in bioequivalence risk assessment and reveal which physico-chemical parameters are most relevant for the development of bioequivalence risk assessment tools for immediate-release products. bioequivalence studies active pharmaceutical ingredients acido-basic characteristics immediate-release products solubility bioekvivalenčne študije aktivne sestavine učinkovin acido-bazične lastnosti sproščanje učinkovin topnost true false true Angleški jezik Slovenski jezik Članek v reviji 2023-11-10 08:31:04 2023-11-10 08:31:08 2023-11-17 03:36:34 0000-00-00 00:00:00 2023 0 0 Str. 211-220 iss. 3 Vol. 23 2023 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 544.351.3:615 1179-6901 10.1007/s40268-023-00426-6 155412483 s40268-023-00426-6.pdf s40268-023-00426-6.pdf 1 5A085521EC11406EF4C6E8865F064967 f51921398897290866f4dee55b878bf989afb603e21f6970af256c323a319737 e84da2d0-8459-11ee-b83b-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=177681 https://link.springer.com/article/10.1007/s40268-023-00426-6 1 1dfd3256-7f9b-11ee-bf5f-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=177529 Fakulteta za farmacijo 0 0 0