Modulating nimodipine crystallinity for enhancing dissolution: development of geriatric-friendly dosage form

Abstract

Background: Instant disintegration of oral disintegrating tablets (ODTs) provides 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. Objective: The objective was to improve nimodipine dissolution rate with the goal of developing ODTs for elderly patients, especially those experiencing neurological deficits. 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 (DSC), 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 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 a molar ratio of 1:1 or nimodipine and tartaric acid at 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 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.