University of Basel, Division of Pharmaceutical Technology, Basel, Switzerland.
Eur J Pharm Sci. 2011 Oct 9;44(3):351-8. doi: 10.1016/j.ejps.2011.08.009. Epub 2011 Aug 25.
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.
简单的油制剂广泛应用于口服药物传递系统，这些系统的命运主要由分散和消化过程决定。目前的工作旨在研究六种疏水性差的药物对中链甘油三酯体外脂肪分解率的浓度效应。将结果与药物对油粘度和表面张力的影响进行了比较。首先通过分子建模对不同的药物进行了表征，并评估了它们对物理油性质的影响。本文采用了毛细管粘度计和动态表面张力计。随后，使用与控温容器相连的自动 pH -stat 滴定仪在生物相关介质中确定了明显的体外脂肪分解率。不同的药物对油的粘度和表面张力表现出不同的影响。然而，所有的药物都显著降低了油的表观脂肪分解率。除了奥利司他，因为直接抑制作用很强，几乎阻断了脂肪分解，所以这种作用在不同的化合物之间非常相似。其他药物可能通过不同的机制影响脂肪分解动力学。根据获得的结果，药物对油粘度或表面张力的影响在降低脂肪分解率方面似乎作用较小。脂肪分解动力学进一步不受药物负荷的影响，这从药物的角度来看是有利的。因此，不同的剂量强度不被认为会改变脂肪分解动力学，这有利于限制体内药物释放的可变性。然而，还需要进一步研究药物在不断变化的消化阶段中的溶解度动力学，以最终评估简单油制剂中剂量强度的潜在影响。
