Mechanisms of dissolution of frusemide/PVP solid dispersions

With a discriminating intrinsic dissolution apparatus the dissolution rates and profiles of frusemide-polyvinylpyrrolidone (PVP) mix and solid dispersion systems (10–100% w/w frusemide) have been examined together with scanning electron photomicrographs (SEM) of the dissolution surfaces of compressed discs before and after dissolution. Solid dispersion systems exhibited higher dissolution rates than corresponding mixes and untreated frusemide. The peak intrinsic dissolution rate, found for both mix and dispersion systems containing 40% w/w frusemide, was attributed to a balance of two opposing factors. In mix systems a dissolution-promoting effect of soluble complex formation with PVP is balanced by a viscosity-related retarding effect of increasing PVP content in the diffusion layer. In dispersion systems a large dissolution-promoting effect of the X-ray amorphous state of the drug at the 40% drug level produces a highly supersaturated diffusion layer demonstrated in time/solubility profiles which is also balanced by the increasing PVP content in the diffusion layer. These findings were further supported by the observed dependence of the dissolution rate on the molecular weight and related solution viscosity of the PVP used to form the X-ray amorphous solid dispersion and mechanical mix, in high polymer content systems. In addition, a filming effect over dissolved compact faces shown by SEM, when the drug level was 40% w/w or less was attributed to a PVP layer covering the dissolving face and the change from a crystalline drug-controlled dissolution mechanism to a polymer controlled system.