Predictive potential of acido-basic properties, solubility and food on bioequivalence study outcome : analysis of 128 studies

Krajcar, Dejan (avtor), Jereb, Rebeka (avtor), Legen, Igor (avtor), Opara, Jerneja (avtor), Grabnar, Iztok (avtor)

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.

• Jezik: Angleški jezik
• Ključne besede: bioequivalence studies, active pharmaceutical ingredients, acido-basic characteristics, immediate-release products, solubility
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2023
• Št. strani: Str. 211-220
• Številčenje: Vol. 23, iss. 3
• PID: 20.500.12556/RUL-152194
• UDK: 544.351.3:615
• ISSN pri članku: 1179-6901
• DOI: 10.1007/s40268-023-00426-6
• COBISS.SI-ID: 155412483
• Datum objave v RUL: 10.11.2023

Gradivo je del revije

• Naslov: Drugs in R&D
• Skrajšan naslov: Drugs R&D
• Založnik: Springer Nature, Adis
• ISSN: 1179-6901
• COBISS.SI-ID: 520363801

Licence

• Licenca: CC BY-NC 4.0, Creative Commons Priznanje avtorstva-Nekomercialno 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by-nc/4.0/deed.sl
• Opis: Licenca Creative Commons, ki prepoveduje komercialno uporabo, vendar uporabniki ne rabijo upravljati materialnih avtorskih pravic na izpeljanih delih z enako licenco.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: bioekvivalenčne študije, aktivne sestavine učinkovin, acido-bazične lastnosti, sproščanje učinkovin, topnost

Projekti

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Številka projekta: P1-0189
• Naslov: Farmacevtska tehnologija: od dostavnih sistemov učinkovin do terapijskih izidov zdravil pri otrocih in starostnikih