Comparison of Hydrophilic and Lipophilic Surfactants for the Improvement of Solubility of BCS Class II Drug by First Generation Solid Dispersion Method

Abstract

Limitation of BCS class-II drugs like diclofenac sodium (DS) can be overcome by using solid
dispersion technique. The purpose of the study was to calculate the effect of molecular weight of different
surfactants on solubility and dissolution behavior of DS. For this purpose, two different types of surfactants
i.e., lipophilic (propylene glycol and span 60) and hydrophilic (polyvinyl pyrrolidone and polyethylene glycol) were used. Solidly dispersed diclofenac sodium was prepared by simple mixing of different ratios of
surfactant. Pure DS and their 1:5 SD-DS were further analyzed by phase solubility studies, FTIR analysis,
while Gibbs free energy was calculated for the confirmation of electrostatic attraction between the surfactant
and DS. Solubility of DS was increased from 12 to 85%, 8 to 53%, 12 to 78% and, 16 to 111% by using PVP,
Span 60, PEG and PG, respectively, showing direct relation of molecular weight of surfactant with solubility.
Dissolution studies showed DS-span 60-5 and DS-PG-5 follow zero order kinetics with 0.456 and 0.953 rate
constants and lowest AIC value of 21.80 and 29.35%, respectively, while DS-PVP-5 and DS-PEG-5 follow
Hixon-Crowell model. FTIR peaks confirmed that all spectra of DS were equivalent to spectra obtained by
the addition of surfactant with peaks at 3260-3265 cm–1, 1640- 1660 cm–1, 1400-1600 cm–1 and 700-800 cm–1.
Stability studies calculations confirmed the stability of DS-PG-5 with 14-month shelf life. Prepared solidly
dispersed DS can be used as an alternative to less soluble DS in the treatment of osteoarthritis and various
inflammatory conditions.