Study of drug concentration effects on in vitro lipolysis kinetics in medium-chain triglycerides by considering oil viscosity and surface tension

Simple oil formulations are widely used in oral drug delivery and the fate of these systems is governed mainly by the dispersion and digestion process. The current work aimed to study concentration effects of six poorly water-soluble drugs on the in vitro lipolysis rate of medium-chain triglycerides. The results were compared with drug effects on oil viscosity and surface tension. First the different drugs were characterized by molecular modeling and their influence on physical oil properties was assessed. Herein capillary viscosimetry was employed as well as dynamic surface tensiometry. Subsequently, an apparent in vitro lipolysis rate was determined in biorelevant medium using an automated pH stat titrator linked to a thermo-controlled vessel. The different drugs exhibited varying effects on oil viscosity and surface tension. However, all drugs significantly lowered the apparent lipolysis rate of the oil. This effect was very similar among the different compounds with exception of orlistat, which practically blocked lipolysis because of a potent direct inhibition. The other drugs affected lipolysis kinetics most likely by different mechanism(s). In light of the obtained results, a drug effect on oil viscosity or surface tension appeared to play a minor role in reducing the lipolysis rate. The lipolysis kinetics was further not affected by the drug load, which was deemed advantageous from a pharmaceutical viewpoint. Different dose strengths are therefore not assumed to alter lipolysis kinetics, which is beneficial for limiting the variability of in vivo drug release. Further studies of drug solubility kinetics in the evolving digestion phases are, however, needed to finally assess potential effects of dosage strength in simple oil formulations. (C) 2011 Published by Elsevier B.V.