Granero Gladys E, Ramachandran Chandrasekharan, Amidon Gordon L
College of Pharmacy, University of Michigan, Ann Arbor, Michigan, USA.
Drug Dev Ind Pharm. 2005 Oct;31(9):917-22. doi: 10.1080/03639040500272108.
The solubility of fenofibrate in pH 6.8 McIlvaine buffers containing varying concentrations of sodium lauryl sulfate was determined. The dissolution behavior of fenofibrate was also examined in the same solutions with rotating disk experiments. It was observed that the enhancement in intrinsic dissolution rate was approximately 500-fold and the enhancement in solubility was approximately 2000-fold in a pH 6.8 buffer containing 2% (w/v) sodium lauryl sulfate compared to that in buffer alone. The micellar solubilization equilibrium coefficient (k*) was estimated from the solubility data and found to be 30884+/-213 L/mol. The diffusivity for the free solute, 7.15x10(-6) cm2/s, was calculated using Schroeder's additive molal volume estimates and Hayduk-Laurie correlation. The diffusivity of the drug-loaded micelle, estimated from the experimental solubility and dissolution data and the calculated value for free solute diffusivity, was 0.86x10(-6) cm2/s. Thus, the much lower enhancement in dissolution of fenofibrate compared to its enhancement in solubility in surfactant solutions appears to be consistent with the contribution to the total transport due to enhanced micellar solubilization as well as a large decrease (approximately 8-fold) in the diffusivity of the drug-loaded micelle.
测定了非诺贝特在含有不同浓度月桂基硫酸钠的pH 6.8 McIlvaine缓冲液中的溶解度。还通过旋转圆盘实验在相同溶液中研究了非诺贝特的溶解行为。观察到，与仅含缓冲液相比，在含有2%（w/v）月桂基硫酸钠的pH 6.8缓冲液中，固有溶解速率提高了约500倍，溶解度提高了约2000倍。根据溶解度数据估算了胶束增溶平衡系数（k*），发现其为30884±213 L/mol。使用施罗德加和摩尔体积估计值和海杜克 - 劳里相关性计算了游离溶质的扩散系数，为7.15×10⁻⁶ cm²/s。根据实验溶解度和溶解数据以及计算得到的游离溶质扩散系数值估算出载药胶束的扩散系数为0.86×10⁻⁶ cm²/s。因此，与非诺贝特在表面活性剂溶液中溶解度的提高相比，其溶解的提高幅度要低得多，这似乎与胶束增溶增强对总传输的贡献以及载药胶束扩散系数大幅降低（约8倍）相一致。
