The class
Lipid-based formulations boost oral exposure of a poorly soluble CETP inhibitor up to 10-fold in preclinical species (J Pharm Sci 2018)
Original title: Oral Delivery of Highly Lipophilic, Poorly Water-Soluble Drugs: Self-Emulsifying Drug Delivery Systems to Improve Oral Absorption and Enable High-Dose Toxicology Studies of a Cholesteryl Ester Transfer Protein Inhibitor in Preclinical Species
BMS-A, a CETP inhibitor, is highly lipophilic (clogP 10.5) with very poor aqueous solubility (less than 0.0001 mg per mL at pH 6.5), giving it low oral exposure when dosed as a cosolvent solution. Researchers screened lipid and cosolvent/surfactant excipients and developed prototype self-emulsifying formulations to enable high-dose toxicology studies. In vitro testing showed these lipid formulations formed fine microemulsions and transferred BMS-A into the aqueous phase after digestion. In dogs dosed at 200 mg per kg, a Gelucire-based formulation gave more than 10-fold higher exposure than the solution formulation, while an olive-oil formulation gave about 7-fold higher exposure in monkeys, enabling toxicology studies of this highly lipophilic CETP inhibitor.
Original abstract
BMS-A is an inhibitor of cholesteryl ester transfer protein and is a highly lipophilic compound (clogP 10.5) with poor aqueous solubility (<0.0001 mg/mL at pH 6.5). The compound exhibits low oral exposure when dosed as cosolvent solution formulations. The purpose of this study was to evaluate lipid-based formulations for enabling high-dose toxicology studies and enhancing toxicology margins of BMS-A in preclinical studies in nonrodent species. The solubility of BMS-A was screened in lipid and cosolvent/surfactant excipients, and prototype formulations were developed. In vitro tests showed that fine/microemulsions were formed after aqueous dilution of lipid formulations, and BMS-A was transferred from oil phase to aqueous phase with enhanced solubility following lipid digestion. When dosed in dogs at 200 mg/kg, a Gelucire-based formulation exhibited more than 10-fold higher exposure compared to the solution formulation and was thus selected for toxicology studies in dogs. For monkeys, an olive oil formulation was developed, and the exposure was about 7-fold higher than that from the solution. In summary, lipid-based drug delivery could be applied in early stages of drug discovery to enhance oral exposure and enable preclinical toxicology studies of highly lipophilic compounds, while facilitating the candidate selection of a molecule which is more specifically designed for bioperformance in a lipid-based drug delivery strategy.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.