Lauroyl polyoxylglycerides, functionalized coconut oil, enhancing the bioavailability of poorly soluble active substances

Pharmaceutical R&D, Gattefossé S.A.S., Saint-Priest, 69804, France

^* vjannin@gattefosse.com

Abstract

Gelucire^® 44/14, a lauroyl polyoxylglycerides obtained by polyglycolysis of hydrogenated coconut oil with PEG-32, is used to increase the oral bioavailability of poorly-water soluble drugs. It is a solid dispersion composed of a PEG ester fraction under a lamellar phase of 120 Å with a helical conformation and an acylglycerol fraction under a hexagonal packing. This excipient spontaneously evolves to its most stable phase of 120 Å after storage at 25 °C for 21 hours leading to physically stable formulations. Gelucire^® 44/14 is a hydrophilic system that hydrates and swells in contact with water and forms cubic mesophases before complete erosion/emulsification. It is also lipolyzed by various enzymes such as gastric lipase or carboxyl ester hydrolase. After an in vitro gastrointestinal lipolysis simulation, the main components remaining are mono and diesters of PEG-32. These amphiphilic metabolites can explain the beneficial role of Gelucire^® 44/14 on the solubility of poorly-water soluble drugs such as cinnarizine even after partial lipolysis of the lipid-based system. Finally that excipient can also increase the bioavailability of active substances by interacting with enterocyte-based proteins like P-glycoprotein or cytochromes P450.