In vitro-In vivo Relationship and Bioequivalence Prediction for Modified-Release Capsules Based on a PBPK Absorption Model
| Autor: | Rebeka Jereb, Bostjan Petek, Jerneja Opara, Igor Legen, Darja Grabnar-Peklar |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Physiologically based pharmacokinetic modelling
Chromatography Ecology Chemistry External validation Pharmaceutical Science Capsules General Medicine Absorption (skin) Aquatic Science Bioequivalence Models Biological IVIVC Pharmacokinetics Intestinal Absorption Solubility Therapeutic Equivalency In vivo Drug Discovery Humans In vitro in vivo Agronomy and Crop Science Ecology Evolution Behavior and Systematics |
| Zdroj: | AAPS PharmSciTech. 21(1) |
| ISSN: | 1530-9932 |
| Popis: | A physiologically based pharmacokinetic (PBPK) absorption model was developed in GastroPlus™ based on data on intravenous, immediate-release (IR), and modified-release (MR) drug products. The predictability of the model was evaluated by comparing predicted and observed plasma concentration profiles; average prediction errors (PE) were below 10%. IVIVR was developed using mechanistic deconvolution for a MR drug product to evaluate the in vivo effect of a proposed change in dissolution specification. The predictability of the IVIVR was evaluated and PE were below 10%; however, external validation was not possible due to the lack of data. The developed PBPK absorption model and IVIVR were used to predict plasma concentration profiles and pharmacokinetic (PK) parameters for a hypothetical formulation with 0% of drug dissolved in 2 h in in vitro dissolution test. Both methods predicted the insignificant effect of a change in in vitro dissolution profile on in vivo product performance. The bioequivalence of a hypothetical formulation to the test product was evaluated using virtual clinical trial. The performed analysis supported the proposed change in dissolution specification. A validated PBPK absorption model was proposed as an adequate alternative to IVIVC, when IVIVC could not have been developed according to the guidelines. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink