Fernandez_2013_Pharm.Res_30_3077

Reference

Title : In vitro digestion of the self-emulsifying lipid excipient Labrasol() by gastrointestinal lipases and influence of its colloidal structure on lipolysis rate - Fernandez_2013_Pharm.Res_30_3077
Author(s) : Fernandez S , Jannin V , Chevrier S , Chavant Y , Demarne F , Carriere F
Ref : Pharm Res , 30 :3077 , 2013
Abstract :

PURPOSE: Labrasol((a)) is a self-emulsifying excipient used to improve the oral bioavailability of poorly water-soluble drugs. It is a mixture of acylglycerols and PEG esters, these compounds being substrates for digestive lipases. The characterization of Labrasol((a)) gastrointestinal lipolysis is essential for understanding its mode of action. METHODS: Labrasol((a)) lipolysis was investigated using either individual enzymes (gastric lipase, pancreatic lipase-related protein 2, pancreatic carboxyl ester hydrolase) or a combination of enzymes under in vitro conditions mimicking first the gastric phase of lipolysis and second the duodenal one. Specific methods for quantifying lipolysis products were established in order to determine which compounds in Labrasol((a)) were preferentially hydrolyzed. RESULTS: Gastric lipase showed a preference for di- and triacylglycerols and the main acylglycerols remaining after gastric lipolysis were monoacylglycerols. PEG-8 diesters were also hydrolyzed to a large extent by gastric lipase. Most of the compounds initially present in Labrasol((a)) were found to be totally hydrolyzed after the duodenal phase of lipolysis. The rate of Labrasol((a)) hydrolysis by individual lipases was found to vary significantly with the dilution of the excipient in water and the resulting colloidal structures (translucent dispersion; opaque emulsion; transparent microemulsion), each lipase displaying a distinct pattern depending on the particle size. CONCLUSIONS: The lipases with distinct substrate specificities used in this study were found to be sensitive probes of phase transitions occurring upon Labrasol((a)) dilution. In addition to their use for developing in vitro digestion models, these enzymes are interesting tools for the characterization of self-emulsifying lipid-based formulations.

PubMedSearch : Fernandez_2013_Pharm.Res_30_3077
PubMedID: 23636839
Gene_locus related to this paper: human-PNLIPRP2

Related information

Substrate Labrasol
Gene_locus Labrasol    human-PNLIPRP2

Citations formats

Fernandez S, Jannin V, Chevrier S, Chavant Y, Demarne F, Carriere F (2013)
In vitro digestion of the self-emulsifying lipid excipient Labrasol() by gastrointestinal lipases and influence of its colloidal structure on lipolysis rate
Pharm Res 30 :3077

Fernandez S, Jannin V, Chevrier S, Chavant Y, Demarne F, Carriere F (2013)
Pharm Res 30 :3077