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In vitro lipolysis/microsomal metabolism approach for the prediction of oral bioavailability of BCS II drugs in lipidic formulations

Publication Date
September 20, 2016
Creators
Description
Lipidic formulations (LFs) are increasingly utilized for the delivery of drugs that belong to class II of the Biopharmaceutics Classification System (BCS). The current work proposes, for the first time, the combination of in vitro lipolysis and microsomal metabolism studies for the quantitative prediction of human oral bioavailability of BCS II drugs administered in LFs. Marinol® and Neoral® were selected as model LFs and their observed oral bioavailabilities (Fobserved) obtained from published clinical studies in humans. Two separate lipolysis buffers, differing in the level of surfactant concentrations, were used for digestion of the LFs. The predicted fraction absorbed (Fabs) was calculated by measuring the drug concentration in the micellar phase after completion of the lipolysis process. To determine first-pass metabolism (Fg∙Fh), drug depletion studies with human microsomes were performed. Clearance values were determined by applying the “in vitro half-life approach”. The estimated Fabs and Fg∙Fh values were combined for the calculation of the predicted oral bioavailability (Fpredicted). Results showed that there was a strong correlation between Fobserved and Fpredicted values only when Fabs was calculated using a buffer with surfactant concentrations closer to physiological conditions. The general accuracy of the predicted values suggests that the novel in vitro lipolysis/metabolism approach could quantitatively predict the oral bioavailability of lipophilic drugs administered in LFs. Collection dates: 2015-2016
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DOI
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Subjects (LCSH)

Drug carriers (Pharma...

Lipolysis

Drugs -- Absorption a...

Drugs -- Absorption a...

Drugs -- Design

Drugs -- Bioavailabil...

Pharmacokinetics

Subjects

in vitro lipolysis, m...

Subjects (JACS)

Subjects Allied to Me...

Subjects (LC)

R Medicine::RS Pharma...

Divisions
University of Nottingham, UK Campus::Faculty of Science::School of Pharmacy
Data type
Excel files with raw and processed data corresponding to the publication Benito-Gallo P., et al. Mol Pharm. (2016)
Funders
Grant Number
EP/I01375X/1
Data collection method
In vitro lipolysis, microsomal incubations, HPLC-UV, HPLC-MS/MS, Graphpad
Resource languages
English
Publisher
The University of Nottingham
Date Issued
August 24, 2016
File(s)
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Name

In vitro lipolysis data and Fabs.xlsx

Description
Experimental data: In vitro lipolysis and calculation of fraction absorbed
Size

88.18 KB

Format

Microsoft Excel XML

Checksum (MD5)

744193df286c999aff46bc38c02bb676

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Microsomal metabolism data and Fpredicted.xlsx

Description
Experimental data: Microsomal metabolism of THC and CsA, and calculation of the predicted oral bioavailability
Size

210.1 KB

Format

Microsoft Excel XML

Checksum (MD5)

3e67161d7c80935b6e96d9633c445220