Preclinical evaluation of new formulation concepts for abiraterone acetate bioavailability enhancement based on the inhibition of pH-induced precipitation

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22340%2F20%3A43920954" target="_blank" >RIV/60461373:22340/20:43920954 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/20:10411762 RIV/00216208:11310/20:10411762

Výsledek na webu

<a href="https://doi.org/10.1016/j.ejpb.2020.04.005" target="_blank" >https://doi.org/10.1016/j.ejpb.2020.04.005</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.ejpb.2020.04.005" target="_blank" >10.1016/j.ejpb.2020.04.005</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Preclinical evaluation of new formulation concepts for abiraterone acetate bioavailability enhancement based on the inhibition of pH-induced precipitation

Popis výsledku v původním jazyce

Abiraterone acetate is a potent drug used for the treatment of metastatic castration resistant prostate cancer. However, currently marketed product containing crystalline abiraterone acetate exhibits strong positive food effect which results in strict dosing regimen. In the present work, a rational approach towards design of novel abiraterone acetate formulations that would allow increased bioavailability on a fasting stomach and thus decreased food effect is presented. Precipitation experiments in biorelevant media were designed to assess pH induced precipitation of the drug and a pool of polymeric excipients was then screened for their potential to inhibit precipitation. The best performing polymeric excipients were subsequently used as carriers for the preparation of amorphous solid dispersions. Two main approaches were followed in order to formulate the drug. The first approach relies on the suppression of precipitation from a supersaturated solution whereas the second one is based on the hypothesis that when the release of the drug is tuned, optimal uptake of the drug can be reached. Optimized formulation prototypes were tested in a rat animal model in an incomplete block, randomized bioequivalence study to assess their relative bioavailability under fasting conditions. We show that both formulation approaches lead to increased bioavailability of abiraterone acetate on a fasting stomach with bioavailability in rats being enhanced up to 250% compared to the original drug product containing crystalline drug.

Název v anglickém jazyce

Preclinical evaluation of new formulation concepts for abiraterone acetate bioavailability enhancement based on the inhibition of pH-induced precipitation

Popis výsledku anglicky

Abiraterone acetate is a potent drug used for the treatment of metastatic castration resistant prostate cancer. However, currently marketed product containing crystalline abiraterone acetate exhibits strong positive food effect which results in strict dosing regimen. In the present work, a rational approach towards design of novel abiraterone acetate formulations that would allow increased bioavailability on a fasting stomach and thus decreased food effect is presented. Precipitation experiments in biorelevant media were designed to assess pH induced precipitation of the drug and a pool of polymeric excipients was then screened for their potential to inhibit precipitation. The best performing polymeric excipients were subsequently used as carriers for the preparation of amorphous solid dispersions. Two main approaches were followed in order to formulate the drug. The first approach relies on the suppression of precipitation from a supersaturated solution whereas the second one is based on the hypothesis that when the release of the drug is tuned, optimal uptake of the drug can be reached. Optimized formulation prototypes were tested in a rat animal model in an incomplete block, randomized bioequivalence study to assess their relative bioavailability under fasting conditions. We show that both formulation approaches lead to increased bioavailability of abiraterone acetate on a fasting stomach with bioavailability in rats being enhanced up to 250% compared to the original drug product containing crystalline drug.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

20401 - Chemical engineering (plants, products)

Projekt

<a href="/cs/project/GX19-26127X" target="_blank" >GX19-26127X: Robotický nano-lékárník: Výrobní procesy budoucnosti pro personalisovaná terapeutika</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

European Journal of Pharmaceutics and Biopharmaceutics

ISSN

0939-6411

e-ISSN

—

Svazek periodika

151

Číslo periodika v rámci svazku

June 2020

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

81-90

Kód UT WoS článku

000532682100009

EID výsledku v databázi Scopus

2-s2.0-85083346899