title: In vitro digestion testing of lipid-based delivery systems: calcium ions combine with fatty acids liberated from triglyceride rich lipid solutions to form soaps and reduce the solubilization capacity of colloidal digestion products.
abstract: In vitro digestion testing is of practical importance to predict the fate of drugs administered in lipid-based delivery systems. Calcium ions are often added to digestion media to increase the extent of digestion of long-chain triglycerides (LCTs), but the effects they have on phase behaviour of the products of digestion, and consequent drug solubilization, are not well understood. This study investigates the effect of calcium and bile salt concentrations on the rate and extent of in vitro digestion of soybean oil, as well as the solubilizing capacity of the digestion products for two poorly water-soluble drugs, fenofibrate and danazol. In the presence of higher concentrations of calcium ions, the solubilization capacities of the digests were reduced for both drugs. This effect is attributed to the formation of insoluble calcium soaps, visible as precipitates during the digestions. This reduces the availability of liberated fatty acids to form mixed micelles and vesicles, thereby reducing drug solubilization. The use of high calcium concentrations does indeed force in vitro digestion of LCTs but may overestimate the extent of drug precipitation that occurs within the intestinal lumen.
authors.affiliation: Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), Melbourne, Victoria, Australia.
authors.forename: Ravi
authors.initials: R
authors.lastname: Devraj
authors.forename: Hywel D
authors.initials: HD
authors.lastname: Williams
authors.forename: Dallas B
authors.initials: DB
authors.lastname: Warren
authors.forename: Anette
authors.initials: A
authors.lastname: Mullertz
authors.forename: Christopher J H
authors.initials: CJ
authors.lastname: Porter
authors.forename: Colin W
authors.initials: CW
authors.lastname: Pouton
mesh_terms: D001647:Bile Acids and Salts / Q000737:chemistry; D002118:Calcium / Q000737:chemistry; D011232:Chemical Precipitation; D003102:Colloids; D003613:Danazol / Q000737:chemistry*; D004063:Digestion; D016503:Drug Delivery Systems; D005227:Fatty Acids / Q000737:chemistry; D011345:Fenofibrate / Q000737:chemistry*; D008055:Lipids / Q000737:chemistry*; D012995:Solubility; D013024:Soybean Oil / Q000378:metabolism; D014280:Triglycerides / Q000737:chemistry
chemical_list: D001647:Bile Acids and Salts; D003102:Colloids; D005227:Fatty Acids; D008055:Lipids; D014280:Triglycerides; D013024:Soybean Oil; D003613:Danazol; D002118:Calcium; D011345:Fenofibrate