Part II: bioavailability in beagle dogs of nimodipine solid dispersions prepared by hot-melt extrusion.
The aim of the present work was to investigate the in vitro dissolution properties and oral bioavailability of three solid dispersions of nimodipine. The solid dispersions were compared with pure nimodipine, their physical mixtures, and the marketed drug product Nimotop. Nimodipine solid dispersions were prepared by a hot-melt extrusion process with hydroxypropyl methylcellulose (HPMC, Methocel E5), polyvinylpyrrolidone/vinyl acetate copolymer (PVP/VA, Plasdone S630), and ethyl acrylate, methyl methacrylate polymer (Eudragit EPO). Previous studies of XRPD and DSC data showed that the crystallinity was not observed in hot-melt extrudates, two T(g)s 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. The dissolution profiles of the three dispersion systems showed that the release was improved compared with the unmanipulated drug. Drug plasma concentrations were determined by HPLC, and pharmacokinetic parameters were calculated after orally administering each preparation containing 60 mg of nimodipine. The mean bioavailability of nimodipine was comparable after administration of the Eudragit EPO solid dispersion and Nimotop, but the HPMC and PVP/VA dispersions exhibited much lower bioavailability. However, the AUC(0-12 hr) values of all three solid dispersions were significantly higher than physical mixtures with the same carriers and nimodipine powder.
Zheng
Xin
X
Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, Liaoning, P.R. China. zhengly03@yahoo.com
Yang
Rui
R
Zhang
Yu
Y
Wang
Zhijun
Z
Tang
Xing
X
Zheng
Liangyuan
L
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; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D004337:Drug Carriers / Q000737:chemistry*; D065347:Hypromellose Derivatives; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D008768:Methylmethacrylates / Q000737:chemistry; D009553:Nimodipine / Q000737:chemistry / Q000493:pharmacokinetics*; D011108:Polymers / Q000737:chemistry*; D011759:Pyrrolidines / Q000737:chemistry; D012995:Solubility; D013607:Tablets; D014753:Vinyl Compounds / Q000737:chemistry
D000179:Acrylates; D002121:Calcium Channel Blockers; D002214:Capsules; D004337:Drug Carriers; D008768:Methylmethacrylates; D011108:Polymers; D011759:Pyrrolidines; D013607:Tablets; D014753:Vinyl Compounds; C402301:poly(vinylpyrrolidone-co-vinyl-acetate); D065347:Hypromellose Derivatives; D009553:Nimodipine; C040833:ethyl acrylate; D008747:Methylcellulose