LAUSR

The impact of surfactants on supersaturation of clotrimazole solutions was systematically evaluated. Four clinically-relevant surfactants, sodium dodecyl sulfate (SDS), vitamin E TPGS, Tween 80 and docusate sodium were studied. The induction time for nucleation and rate of desupersaturation were determined at a supersaturation ratio of 90% amorphous solubility. Measurement was also performed in the presence of pre-dissolved hydroxypropyl methylcellulose acetate succinate (HPMCAS) to study the effect of surfactant-polymer interaction on desupersaturation. The four surfactants showed varied effects on desupersaturation. From supersaturation maintenance perspective, in the presence of HPMCAS, the rank order for the four surfactants was found to be: docusate sodium > vitamin E TPGS > SDS > Tween 80. Given the importance of maintaining supersaturation and varied effect of surfactants on nucleation kinetics and desupersaturation rate, a careful examination of API, polymer and surfactant interaction on an individual basis is recommended for selecting an appropriate surfactant for use in amorphous solid dispersion (ASD) formulation.