Torcetrapib
Self-emulsifying formulation cuts the food effect of torcetrapib from 5-fold to 3-fold in dogs (Int J Pharm 2008)
Original title: Development of a self-emulsifying formulation that reduces the food effect for torcetrapib
Because torcetrapib is a highly lipophilic, water-insoluble CETP inhibitor whose early clinical trials showed a substantial food effect on absorption, researchers developed self-emulsifying drug delivery system (SEDDS) formulations to reduce this effect and increase the dose per capsule. A formulation of medium-chain triglyceride, triacetin, polysorbate 80, and Capmul MCM (MTPC) increased fasted-state exposure in dogs, reducing the food effect from 5-fold to 3-fold at a 90 mg dose, and self-emulsifying formulations generally accelerated absorption and reduced variability. The lipophilic cosolvent triacetin allowed a 2-fold increase in dose per capsule, and absorption increased with Cremophor RH40 content, eliminating the food effect entirely at 50% Cremophor RH40 (30 mg dose), though high polar-surfactant content worsened dose proportionality, unlike the well-behaved MTPC formulation. The authors note in vitro lipolysis studies were ongoing to better relate these in vitro findings to in vivo torcetrapib absorption.
Original abstract
Torcetrapib is a highly lipophilic (Clog P=7.45) and water insoluble cholesteryl ester transfer protein (CETP) inhibitor developed for the treatment of atherosclerosis. Self-emulsifying drug delivery system (SEDDS) formulations have been developed to reduce the food effect observed in early clinical trials using medium chain triglyceride (MCT) softgels and to increase the dose per capsule. MCT/Triacetin/Polysorbate 80/Capmul MCM (20/30/20/30) (MTPC) increased fasted exposure and thus reduced the food effect from 5- to 3-fold in dogs at a dose of 90 mg. Self-emulsifying formulations also accelerated absorption and generally decreased variability. Use of the lipophilic, GRAS cosolvent triacetin allowed a 2-fold increase in the dose per capsule. For the three formulations evaluated in dogs that showed significant differences in absorption, emulsion droplet size did not appear to play a significant role. Absorption did increase with Cremophor RH40 content, and at 50% Cremophor RH40 there was no food effect (at 30 mg). High polar surfactant content also resulted in poor dose proportionality, while there was good dose proportionality for MTPC. Studies of in vitro lipolysis are being conducted to aid in understanding the in vitro/in vivo relationships for torcetrapib SEDDS absorption.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.