Predictive Potential of BCS and Pharmacokinetic Parameters on Study Outcome: Analysis of 198 In Vivo Bioequivalence Studies

Krajcar, Dejan; Grabnar, Iztok; Jereb, Rebeka; Legen, Igor; Opara, Jerneja

doi:10.1007/s13318-023-00821-z

Cited by 1 publication

(2 citation statements)

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“…We have previously presented results from a comprehensive study on a real set of bioequivalence study data and assessed the association between various pharmacokinetic parameters/active pharmaceutical ingredient (API) characteristics and bioequivalence study outcome [ 8 ]. Poorly soluble APIs resulted in non-bioequivalence study outcome significantly more often than highly soluble APIs.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, the aim of this analysis was to extend our previous research [ 8 ] and explore the association between additional chemical/biopharmaceutical properties (solubility, logP, effective permeability, Tm, p K a and acido-basic properties) of poorly soluble APIs and their association with non-bioequivalence study outcome in fasting and fed conditions. This could help to further differentiate poorly soluble APIs with regards to bioequivalence outcome and clarify which API parameters are relevant for bioequivalence risk assessment.…”

Section: Introductionmentioning

confidence: 99%

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Predictive Potential of Acido-Basic Properties, Solubility and Food on Bioequivalence Study Outcome: Analysis of 128 Studies

Krajcar

Jereb²,

Legen³

et al. 2023

Drugs R D

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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 (p K a) 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. Supplementary Information The online version contains supplementary material available at 10.1007/s40268-023-00426-6.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%