Dissolution and solubility behavior of fenofibrate in sodium lauryl sulfate solutions.
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.
Granero
Gladys E
GE
College of Pharmacy, University of Michigan, Ann Arbor, Michigan, USA. glagra@dqo.fcq.unc.edu.ar
Ramachandran
Chandrasekharan
C
Amidon
Gordon L
GL
D002021:Buffers; D002851:Chromatography, High Pressure Liquid; D004058:Diffusion; D011345:Fenofibrate / Q000737:chemistry*; D000960:Hypolipidemic Agents / Q000737:chemistry*; D010710:Phosphates; D012967:Sodium Dodecyl Sulfate; D012995:Solubility; D012996:Solutions
D002021:Buffers; D000960:Hypolipidemic Agents; D010710:Phosphates; D012996:Solutions; D012967:Sodium Dodecyl Sulfate; D011345:Fenofibrate