Modulating Nimodipine Crystallinity for Enhancing Dissolution: Development of Geriatric-Friendly Dosage Form

Abstract

Background: Instant disintegration of oral disintegrating tablets (ODTs) provides a greater chance for buccal absorption, avoiding presystemic metabolism of nimodipine. In addition, ODT can be easily dispersed in suitable liquid before delivery via nasogastric tube in critical care setting. Methods: Drop assisted co-grinding of nimodipine with glycine (at molar ratios 1:1, 1:2 and 1:3) or tartaric acid (at molar ratios 1:0.5, 1:1, 1:2, 1:3, and 1:4) was performed. Solid state characterization and in vitro dissolution studies were employed. The optimized formulations were employed to prepare ODTs using suitable excipients. Results: The prepared formulations improved drug dissolution compared to unprocessed and wet ground nimodipine. Fourier–transform infrared spectroscopy, differential scanning calorimetry, powder X-ray diffraction and scanning electron microscopy suggested transformation of the crystalline structure after co-processing. This was due to salt formation in case of tartaric acid and the formation of new crystalline species/ size reduction in case of glycine. These changes were associated with dissolution enhancement. Formulations with highest release efficiency (nimodipine and glycine with a molar ratio of 1:1 or nimodipine and tartaric acid at a molar ratio of 1:3) were successively incorporated in ODTs which showed fast liberation of nimodipine and dissolution efficiency values of 76 + 0.6% and 73.3 + 1.7% for the tablets containing glycine or tartaric acid respectively. Conclusion: The study introduced a simple co-grinding approach for dissolution enhancement of nimodipine with high scaling up potential. The developed tablets will increase patient compliance with expected improved bioavailability.

Keywords

• nimodipine
• glycine
• tartaric acid
• wet co-grinding
• neurological deficits
• rapidly dissolving tablet