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Exploring the utility of the Chasing Principle:influence of drug-free SNEDDS composition on solubilization of carvedilol, cinnarizine and R3040 in aqueous suspension

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Acta Pharmaceutica Sinica B 2019年第1期9卷 194-201页

作者： Scheyla Daniela Siqueira J?rgensen Thomas Rades Huiling Mu Kirsten Graeser Anette Müllertz Department of Pharmacy Faculty of Health and Medical Sciences University of Copenhagen Roche Pharma Research and Development Therapeutic Modalities Roche Innovation Center Basel

This study assessed the influence of the composition of drug-free SNEDDS co-dosed with aqueous suspensions of carvedilol(CAR), cinnarizine(CIN) or R3040 on drug solubilization in a twocompartment in vitro lipolysis model. Correlation of drug log P or solubility in SNEDDS with drug solubilization during in vitro lipolysis in the presence of drug-free SNEDDS was assessed. SNEDDS with varying ratios of soybean oil:Maisine 35-1(1:1, w/w) and Kolliphor RH40, with ethanol at 10%(w/w) were used. SNEDDS were named F65, F55 and F20(numbers refer to the percentage of lipids) and aqueous suspensions without drug-free SNEDDS(F0) were also analyzed. While the ranking order of drug solubilization was F65? F55? F204F0 for CAR; F65? F554F204F0 for CIN and F65? F55? F204F0 for R3040-with higher CAR solubilization than for R3040 and CIN-the ranking of S_(eq)of CAR, CIN and R3040 in SNEDDS was F65 o F55o F20, F65? F554F20 and F654F554F20, respectively. Therefore, the composition of SNEDDS influenced the solubilization of CIN, but not CAR and R3040. Furthermore, high S_(eq) in SNEDDS did not reflect high drug solubilization. As CAR(log P 3.8) showed higher solubilization than CIN(log P 5.8) and R3040(log P 10.4), a correlation between drug log P and drug solubilization was observed.

关键词： Self-nanoemulsiying drug delivery system(SNEDDS) Chasing principle two-compartment in vitro lipolysis Rat gastrointestinal conditions Drug solubilization

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