Predicting the effect of prandial stage and particle size on absorption of ODM-204.

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http://hdl.handle.net/10138/339065

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Ojala , K E M , Schilderink , R , Nykänen , P , van Veen , B , Malmström , C , Juppo , A & Korjamo , T 2020 , ' Predicting the effect of prandial stage and particle size on absorption of ODM-204. ' , European Journal of Pharmaceutics and Biopharmaceutics , vol. 156 , pp. 75-83 . https://doi.org/10.1016/j.ejpb.2020.08.011

Title: Predicting the effect of prandial stage and particle size on absorption of ODM-204.
Author: Ojala, Krista E M; Schilderink, Ronald; Nykänen, P; van Veen, Bert; Malmström, Chira; Juppo, Anne; Korjamo, Timo
Contributor organization: Division of Pharmaceutical Chemistry and Technology
Helsinki One Health (HOH)
Drug Research Program
Pharmaceutical Design and Discovery group
Anne Juppo / Principal Investigator
Date: 2020-11
Language: eng
Number of pages: 9
Belongs to series: European Journal of Pharmaceutics and Biopharmaceutics
ISSN: 0939-6411
DOI: https://doi.org/10.1016/j.ejpb.2020.08.011
URI: http://hdl.handle.net/10138/339065
Abstract: The prediction of absorption properties plays a key role in formulation development when the compound under development shows poor solubility and its absorption is therefore presumed to be solubility limited. In our work, we combined and compared data obtained from in vitro dissolution tests, transit intestinal model studies (TIM -1) and physiologically based pharmacokinetic modelling. Our aim was to determine the ability of these methods to predict performance of poorly soluble lipophilic weak base in vivo. The validity of the predictive methods was evaluated against the in vivo clinical pharmacokinetic (PK) data obtained after administration of the first test formulation, Tl. The aim of our study was to utilize the models in evaluating absorption properties of the second test formulation, T2, which has not yet been clinically administered. The compound in the studies was ODM-204, which is a novel, orally administered, investigational, nonsteroidal dual inhibitor of CYP17A1 and androgen receptor. Owing to its physicochemical properties ODM-204 is prone to low or variable bioavailability. The models examined provided congruent data on dose dependent absorption, food effect at a dose of 200 mg and on the effect of API (active pharmaceutical ingredient) particle size on absorption. Our study shows that the predictive tools of in vitro dissolution, TIM-1 system and the PBPK (physiologically based pharmacokinetic) simulation, showed predictive power of different mechanisms of bioavailability and together provided valuable information for decision making.
Subject: 317 Pharmacy
Absorption
Dissolution
PBPK modeling
Prediction of fraction absorbed
Transit intestinal model
IN-VIVO PERFORMANCE
BIOPHARMACEUTICS TOOLS PROJECT
DOSAGE FORMS
VITRO MODELS
DRUG
SUPERSATURATION
STRATEGIES
DISCOVERY
SYSTEM
IMI
Peer reviewed: Yes
Rights: cc_by_nc_nd
Usage restriction: openAccess
Self-archived version: acceptedVersion


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