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Original Research

Comparisons of in vitro Fick’s first law, lipolysis, and in vivo rat models for oral absorption on BCS II drugs in SNEDDS

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Pages 5623-5636 | Published online: 23 Jul 2019
 

Abstract

Purpose

The objective of this study was to compare the in vitro Fick’s first law, in vitro lipolysis, and in vivo rat assays for oral absorption of Biopharmaceutical Classification Systems Class II (BCS II) drugs in self-nanoemulsifying drug delivery system (SNEDDS), and studied drugs and oils properties effects on the absorption.

Methods

The transport abilities of griseofulvin (GRI), phenytoin (PHE), indomethacin (IND), and ketoprofen (KET) in saturated water solutions and SNEDDS were investigated using the in vitro Madin-Darby canine kidney cell model. GRI and cinnarizine (CIN) in medium-chain triglycerides (MCT)-SNEDDS and long-chain triglycerides (LCT)-SNEDDS were administered in the in vivo SD rat and in vitro lipolysis models to compare the oral absorption and the distribution behaviors in GIT and build an in vitro-in vivo correlation (IVIVC).

Results

In the cell model, the solubility of GRI, PHE, IND, and KET increased 6–8 fold by SNEDDS, but their permeability were only 18%, 4%, 8%, and 33% of those of their saturated water solutions, respectively. However, in vivo absorption of GRI-SNEDDS was twice that of the GRI suspension and those of CIN-SNEDDS were 15–21 fold those of the CIN suspension. In the lipolysis model, the GRI% in aqueous and pellet phases of MCT were similar to that in LCT. In contrast, the CIN% in the aqueous and pellet phases were decreased but that of the lipid phase increased. In addition, an IVIVC was found between the CIN% in the lipid phase and in vivo relative oral bioavailability (Fr).

Conclusion

The in vitro cell model was still a suitable tool to study drug properties effects on biofilm transport and SNEDDS absorption mechanisms. The in vitro lipolysis model provided superior oral absorption simulation of SNEDDS and helped to build correlation with in vivo rats. The oral drug absorption was affected by drug and oil properties in SNEDDS.

Acknowledgment

This work was supported by the National Natural Science Foundation of China (No. 81373361).

Abbreviation list

SNEDDS, self-nanoemulsifying drug delivery system; BCS II, Biopharmaceutical Classification Systems Class II; GRI, griseofulvin; PHE, phenytoin; IND, indomethacin; KET, ketoprofen; CIN, cinnarizine; GRI%, griseofulvin distribution percentage content; CIN%, cinnarizine distribution percentage content; GIT, gastrointestinal tract; MCT, medium-chain triglycerides; LCT, long-chain triglycerides; IVIVC, in vitro-in vivo correlation; Fr, relative oral bioavailability.

Disclosure

The authors report no conflicts of interest in this work.