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• W2068156721 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." @default.
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• W2068156721 date "2008-03-03" @default.
• W2068156721 modified "2023-10-14" @default.
• W2068156721 title "Development of a self-emulsifying formulation that reduces the food effect for torcetrapib" @default.
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• W2068156721 doi "https://doi.org/10.1016/j.ijpharm.2007.09.015" @default.
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