Nimodipine semi-solid capsules containing solid dispersion for improving dissolution.
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 30min). 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 20min). In addition, the relative bioavailability of the NMD-SSC (test) and Nimotop (reference) was determined in beagle dogs after a single dose (120mg 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-infinity)=2488+/-433nghmL(-1), Cmax=321+/-78ngml(-1)) and Nimotop (AUC0-infinity=2272+/-398nghmL(-1), Cmax=293+/-73ngmL(-1)) (P>0.05). However, the apparent rate of absorption of NMD from NMD-SSC (tmax=1.3h) was markedly faster than that from Nimotop (tmax=3.1h) (P<0.05), which indicates that as a fast release preparation, NMD-SSC is well absorbed.
Sun
Yunzhe
Y
School of Pharmacy, Department of Pharmaceutics, Shenyang Pharmaceutical University, No. 103 Wenhua Road, Shenyang 110016, PR China.
Rui
Yang
Y
Wenliang
Zhou
Z
Tang
Xing
X
D000085:Acetates / Q000737:chemistry; D000179:Acrylates / Q000737:chemistry; D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000493:pharmacokinetics*; D002214:Capsules; D018592:Cross-Over Studies; D004285:Dogs; D004337:Drug Carriers / Q000737:chemistry*; D006358:Hot Temperature; D009553:Nimodipine / Q000737:chemistry / Q000493:pharmacokinetics*; D011108:Polymers / Q000737:chemistry; D011205:Povidone / Q000031:analogs & derivatives / Q000737:chemistry; D011897:Random Allocation; D012995:Solubility
D000085:Acetates; D000179:Acrylates; D002121:Calcium Channel Blockers; D002214:Capsules; D004337:Drug Carriers; C477020:Eudragit E100; D011108:Polymers; C525248:copolyvidonum Plasdone S-630; D009553:Nimodipine; D011205:Povidone