Dissolution and Solubility Behavior of Fenofibrate in Sodium Lauryl Sulfate Solutions

Abstract

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.

Assessment of Age-Related Changes in Pediatric Gastrointestinal Solubility

“…Water was ultra-pure (Milli-Q) laboratory grade. Dialysis tubing (12)(13)(14),000 Da MWCO) was acquired from Medicell Membranes Ltd., London, England. Equipment utilized in the current investigation included a Buchi R114 Rotavapor (Flawil, Switzerland), a Beckman Coulter J2-MC centrifuge (High Wycombe, England), a Mettler Toledo SevenCompact S210 pH meter (Schwerzenbach, Switzerland), an Advanced Instruments Inc. micro-osmometer Model 3300 (Norwood, MA) and an Agilent Technologies 1200 series HPLC system (Santa Clara, CA): binary pump (G1212A), autosampler (G1329A), thermostatted column compartment (G1316A), and diode array detector (G1315D).…”

“…Solubility assessments for all compounds, with the exception of fenofibrate, were conducted following a 24 h dwell period. For fenofibrate, previous investigations have employed longer dwell periods (i.e., 48-72 h) in order to achieve equilibrium solubility (14,15). Correspondingly, a dwell period of 72 h was utilized in this investigation.…”

Surface-Active Derivative of Inulin (Inutec® SP1) Is a Superior Carrier for Solid Dispersions with a High Drug Load

“…For fenofibrate, the HPLC analysis was performed according to Granero et al 16 with some modifications, the mobile phase consisted of acetonitrile and 0.02 M phosphoric acid solution (70:30, v/v), and at a flow rate of 1.2 mL/min. The detection wavelength was 286 nm.…”

Dissolution study and thermal analysis of fenofibrate–Pluronic F127 solid dispersions

“…Fenofibrate (FEN) (isopropyl ester of 2-[4-(4-chloro-benzoyl) phenoxy]-2-methylpropanoic acid) is a Biopharmaceutical Classification System (BCS) class-II, lowsolubility, high-permeability hypolipidemic drug [1]. It is used to treat hypercholesterolemia, heart disease, and diabetic complications [2].…”