The impact of quantity of lipid based formulations with different compositions on the oral absorption of ritonavir: A trade-off between apparent solubility and permeability.

In this study, the effect of the quantity of lipid-based formulations (LBFs) on the oral absorption of ritonavir (RTV), a model for poorly water-soluble drugs, was investigated. Two types of LBFs, comprising short- and medium-chain lipids (LBF-SMC) and long-chain lipids (LBF-LC) loaded with different masses of RTV, were prepared. Then, the respective LBFs were dispersed in distilled water at concentrations of 1.0, 2.0, and 3.0% w/w, which provided the same drug concentration for all formulations. When 1.0% LBF-SMC and LBF-LC were orally administered to rats, the oral absorption was significantly improved compared with that of the suspension (a reference formulation) because of enhanced solubilization of RTV in the gastrointestinal tract; however, this improvement was lower for LBF-LC than for LBF-SMC. The oral absorption decreased with increasing LBF concentration for both LBF-SMC and LBF-LC. The in vitro permeation in sequence with in vitro digestion revealed that this phenomenon was caused by a reduction in the free drug concentration in the gastrointestinal tract. Moreover, the effect of decreasing the free concentration was more remarkable for LBF-LC than for LBF-SMC because of the greater solubilization capacity of LC digestion products. These findings may be useful for designing improved drug delivery systems. Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.

Citation

Yusuke Tanaka, Hirotaka Doi, Takeru Katano, Satoshi Kasaoka. The impact of quantity of lipid based formulations with different compositions on the oral absorption of ritonavir: A trade-off between apparent solubility and permeability. European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 2022 Jan 01;168:106079

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PMID: 34843915

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