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Abstract

The influence of lipid vehicles on the intestinal absorption of Ciclosporin was studied in vitro. The effect of the intestinal lipid digestion was considered on the partition of the drug from olive oil or middle-chain triglyceride (MCT) into phases of simulated intestinal content. The phases obtained after ultracentrifugation were analyzed for their Ciclosporin content and characterized for their lipid classes. For both lipid vehicles the presence of lipolysis products did not promote the partition of the drug into the aqueous phase. The absorption in vivo was not related to the drug amount in the aqueous phase and in the oil phase. Therefore, phase quantification in vitro cannot simulate the dynamics of in vivo absorption events following application of a poorly water-soluble drug in a lipid vehicle.

In vitro–in vivo evaluation of lipid based formulations of the CETP inhibitors CP-529,414 (torcetrapib) and CP-532,623

“…Labrafil M 2125 CS is a complex mixture of materials including a mixture of mono, di and trigycerides of C18:2 (linoleic acid) and mono and di-esters of PEG300. Notably, the lipids in Labrafil M 2125 CS are long chain lipids and previous studies have shown that these are less readily digested in vitro than their medium chain comparators (32,40). Labrafil M 2125 CS also forms a relatively course dispersion on initial dilution into aqueous media.…”

Physicochemical and Physiological Mechanisms for the Effects of Food on Drug Absorption: The Role of Lipids and pH

“…Reports exist where in vitro lipid digestion models 154,155 have been used to assess the rate and extent of transfer of drugs from a prospective formulation, through the respective colloidal phases, to the final mixed micellar phase. 156 It has been proposed that the rate of transfer may be a crucial ratedetermining step in the absorption of highly lipophilic drugs, particularly from lipid-based formulations. 156 There are various animal models available for the confirmation of intestinal lymphatic transport 134,157 ; however, the best first step is estimation of the potential for transport from consideration of the partition coefficient and lipid solubility of the drugs.…”

“…156 It has been proposed that the rate of transfer may be a crucial ratedetermining step in the absorption of highly lipophilic drugs, particularly from lipid-based formulations. 156 There are various animal models available for the confirmation of intestinal lymphatic transport 134,157 ; however, the best first step is estimation of the potential for transport from consideration of the partition coefficient and lipid solubility of the drugs. If such calculations indicate that lymphatic transport may be a contributor to oral bioavailability, then further confirmatory experiments should be undertaken.…”

Lipid-based Formulations for Danazol Containing a Digestible Surfactant, Labrafil M2125CS: In Vivo Bioavailability and Dynamic In Vitro Lipolysis

“…Further, some excipients are hydrolyzed in the gastrointestinal tract by lipases, thereby changing the solubilizing environment (17)(18)(19)(20). With the aim of distinguishing between the performances of lipidbased formulations in vivo and thereby facilitate the formulation development, several in vitro digestion models have been developed (1,(21)(22)(23)(24). Attempts have been made to correlate the solubilization of the drug in the aqueous phase generated during in vitro lipolysis with the in vivo performance of lipidbased formulations.…”