Dissolution and solubility behavior of fenofibrate in sodium lauryl sulfate solutions

被引:65
作者
Granero, GE [1 ]
Ramachandran, C [1 ]
Amidon, GL [1 ]
机构
[1] Univ Michigan, Coll Pharm, Ann Arbor, MI 48109 USA
关键词
fenofibrate; intrinsic dissolution rate; micellar solubilization; sodium lauryl sulfate;
D O I
10.1080/03639040500272108
中图分类号
R914 [药物化学];
学科分类号
100701 [药物化学];
摘要
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, 7.15 x 10(-6) cm(2)/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 0.86 x 10(-6) cm(2)/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 (similar to 8-fold) in the diffusivity of the drug-loaded micelle.
引用
收藏
页码:917 / 922
页数:6
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