Nimodipine semi-solid capsules containing solid dispersion for improving dissolution

Abstract

The aim of this study was to improve the dissolution and, therefore, bioavailability of the poorly water-soluble and highly permeable drug nimodipine (NMD). Present research involved the preparation of a solid dispersion (SD) consisting of NMD, Eudragit-E100 and Plasdone-S630 by hot-melt extrusion (HME). Compared with pure drug and physical mixture, the dissolution of NMD was enhanced dramatically (about 80% within 30 min). Adding the nimodipine solid dispersion (NMD-SD) powder to a mixture of Plasdone-S630 and PEG400, and then transferring it to hard HPMC capsules, resulted in nimodipine semi-solid capsules (NMD-SSC). The dissolution from NMD-SSC was increased further (about 95% in 20 min). In addition, the relative bioavailability of the NMD-SSC (test) and Nimotop ® (reference) was determined in beagle dogs after a single dose (120 mg NMD) in a randomized crossover, own-control study. The results suggested that there was no significant difference in the areas under the plasma concentration–time curve and the mean peak concentration between NMD-SSC (AUC 0–∞ = 2488 ± 433 ng h mL −1, C max = 321 ± 78 ng ml −1) and Nimotop ® (AUC 0–∞ = 2272 ± 398 ng h mL −1, C max = 293 ± 73 ng mL −1) ( P > 0.05). However, the apparent rate of absorption of NMD from NMD-SSC ( t max = 1.3 h) was markedly faster than that from Nimotop ® ( t max = 3.1 h) ( P < 0.05), which indicates that as a fast release preparation, NMD-SSC is well absorbed.