Effects of Polymer/Surfactant as Carriers on the Solubility and Dissolution of Fenofibrate Solid Dispersion.

ABSTRACT

The purpose of this work is to investigate the effects of polymer/surfactant as carriers on the solubility and dissolution of fenofibrate solid dispersions (FF SDs) with the aid of systematic research on the physicochemical properties of the polymer/surfactant system and further highlight the importance of studying polymer/surfactant interaction in the preformulation. The critical micelle concentration (CMC) of sodium lauryl sulfate (SLS) and critical aggregation concentration (CAC) of polymer/SLS solutions were obtained through conductivity measurement. Meanwhile, surface tension, viscosity, morphology, and wettability of polymer/SLS with different weight ratios of SLS were analyzed to screen out the suitable content of SLS (weight%, 5% in carriers) incorporated in SDs. Polymer/SLS coprecipitate and FF SDs were prepared by the solvent evaporation method. The results from differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis showed that FF was molecularly dispersed in SDs. Compared to the solubility of FF in povidone/SLS (PVP/SLS) solutions, the increment of FF solubility in copovidone/SLS (VA64/SLS) solutions was due to the formation of free SLS micelles, which have been confirmed by transmission electron microscopy (TEM). Particularly, the wettability of FF SDs and physical mixtures (PMs) was also determined by the sessile drop technique. A linear relationship between the wettability of carriers and that of FF SDs was found, which revealed the significant role of carriers on the surface composition of FF SDs. As the molecular weight of PVP increased, the wettability of carriers decreased, thus leading to the reduction of the dissolution rate of SDs. Although the presence of SLS did not enhance the dissolution of FF SDs, it increased the amount of drug released at the initial stage. All these results indicated that the polymer/SLS interaction would affect the performance of SDs; hence, it was necessary to study their properties in the preformulation.