Preparation and Evaluation of Controlled-Release Solid Dispersion Granules Containing a Poorly Water-Soluble Drug, Hydrated Silicon Dioxide, and Polyvinylpyrrolidone

Abstract

The study aim was to develop controlled-release, solid dispersion granules containing a poorly water-soluble drug, Hydrated Silicon Dioxide (HSD), and Polyvinylpyrrolidone (PVP), and to elucidate the mechanism underlyingsustained release from the soliddispersion granules. To achieve this purpose, we used the wet granulation method to prepare the first-release granules containing a poorly water-soluble drug and HSD. Then, the effect of PVP on the dissolution of the poorly water-soluble drug was estimated. Initially, the selection of a binder and contentsof drug and binder were investigated to determine the optimum formulation fora rapidly dissolving granule with HSD. Firstrelease granules containing Nifedipine (NIF) as a poorly water-soluble drug, erythritol as a binder, and HSD were developed. Differential scanning calorimetry confirmed reduced NIF crystallinity in the granules. To investigate the first-release granules’ applicabilityto other drugs, six poorly water-soluble drugs (griseofulvin, indomethacin, ibuprofen, carbamazepine, progesterone, and phenytoin) were prepared. Rapid dissolutionof all tested drugs from the granule with the same NIF formulation was observed. These findings suggest that HSD is useful for improving dissolution ratesof poorly water-soluble drugs insoliddispersion granules. Next, we investigated PVP’s effect on the dissolution of drug from the first-release granules. The effects of PVP on sustained release from the granules containing the seven drugs weredivided into three types: Type 1 was no effect (rapid dissolution), type 2 was a middle effect, and type 3 was a strong effect (sustained release). To elucidate the mechanism underlying sustained release from the solid dispersion granules, the intermolecular interactions between the drugs and HSD or PVP were investigated by Fourier transform infrared spectroscopy. The results suggested that the balance between the interaction of a drug and HSD and the interaction of a drug and PVP is important for sustained release of the drug.