The objective of this study was to increase the solubility of two poorly water soluble drugs, namely Diflunisal USP and Mefenamic Acid USP, by the formation of ternary solid dispersion granules with a dispersion carrier and an adsorbent. The study also includes characterization of the ternary solid dispersion granules for their physicochemical properties initially and after storage for 3 months. The dispersion carrier used for this study was Gelucire 50/13® and the adsorbent was Neusilin US2®. The fusion (hot melt) granulation method was used to prepare the ternary solid dispersion granules. Various characterization techniques were used to characterize the solid dispersion including Differential Scanning Calorimetry (DSC), X-Ray Powder Diffraction (XRPD), Fourier Transform Infrared Spectroscopy (FTIR), Scanning Electron Microscopy (SEM) and in vitro dissolution studies.
The DSC data represents the ternary mixture of the drug (diflunisal or mefenamic acid), dispersion carrier (Gelucire50/13®) and adsorbent (Neusilin US2®), which formed the solid dispersion. The XRPD results confirmed the highly crystalline nature of the pure drug (diflunisal or mefenamic acid) and the conversion of the drug to the amorphous state in the solid dispersions. The FTIR study reveals hydrogen bonding which leads to solid dispersion formation. No other chemical interaction was observed between the components of the ternary solid dispersion granule. The SEM study provided evidence of the highly crystalline nature for the pure drug and the amorphous nature for the ternary solid phase dispersion. In vitro dissolution data reveals a significant increase in drug solubility from the ternary solid dispersion granule as compared to the solubility for the pure drug. The ternary solid dispersion granule formed for diflunisal and mefenamic acid were highly amorphous and able to significantly increase the solubility of each drug.
Stability studies were performed for the solid dispersion of both the drugs (diflunisal and mefenamic acid) by subjecting them to different isothermal temperatures (25°C, 30°C, 35°C and 40°C) and relative humidity conditions (22.5% RH, 52.89% RH, 75.29% RH and 100% RH) for three months. The solid dispersion for both drugs (diflunisal and mefenamic acid) remained unaffected by the temperature and humidity conditions to which they were exposed throughout the three months period. Thus, in this study, the ternary solid dispersion granules for the two poorly water soluble drugs (diflunisal and mefenamic acid) were formulated which showed an increased dissolution as well as rate. The solid dispersion granules were extremely stable for three month under accelerated temperature and humidity conditions.