Part I: Characterization of Solid Dispersions of Nimodipine Prepared by Hot-melt Extrusion

ABSTRACT The purpose of this study was to prepare and characterize solid dispersions of nimodipine with hydroxypropyl methylcellulose (HPMC, Methocel E5), polyvinylpyrrolidone/vinyl acetate copolymer (PVP/VA, Plasdone S630®), and ethyl acrylate, methyl methacrylate polymer (Eudragit® EPO). The goal was to investigate whether the solid dispersion prepared by hot-melt extrusion can improve the dissolution rate of nimodipine. The dissolution results indicated that three polymers are suitable carriers to enhance the in vitro dissolution rate of nimodipine in pH 4.5 medium. The solubility research and solubility parameters calculation was corresponded with dissolution data. XRPD and DSC data showed that the crystallinity was not observed in hot-melt extrudates. NMD acted as a plasticizer for PVP/VA and EPO and was miscible with the polymers as well as 10% NMD-HPMC systems, because a single Tg was observed in these extrudates. However, two Tgs were observed in the 30 and 50% NMD-HPMC samples, indicating phase separation. The weakening and shift of the N–H stretching vibration of the secondary amine groups of nimodipine as determined by FT-IR proved hydrogen bonding between the drug and polymers in the solid dispersion.

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