Preclinical evaluation of new formulation concepts for abiraterone acetate bioavailability enhancement based on the inhibition of pH-induced precipitation
The result's identifiers
Result code in 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>
Alternative codes found
RIV/00216208:11110/20:10411762 RIV/00216208:11310/20:10411762
Result on the web
<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>
Alternative languages
Result language
angličtina
Original language name
Preclinical evaluation of new formulation concepts for abiraterone acetate bioavailability enhancement based on the inhibition of pH-induced precipitation
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
20401 - Chemical engineering (plants, products)
Result continuities
Project
<a href="/en/project/GX19-26127X" target="_blank" >GX19-26127X: The robotic nano-pharmacist: Next-generation manufacturing processes for personalised therapeutic agents</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
European Journal of Pharmaceutics and Biopharmaceutics
ISSN
0939-6411
e-ISSN
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Volume of the periodical
151
Issue of the periodical within the volume
June 2020
Country of publishing house
US - UNITED STATES
Number of pages
10
Pages from-to
81-90
UT code for WoS article
000532682100009
EID of the result in the Scopus database
2-s2.0-85083346899