CONTROLLED RELEASE OF NIFEDIPINE FROM GELATIN MICROSPHERES AND MICROCAPSULES - INVITRO KINETICS AND PHARMACOKINETICS IN MAN

被引:14
作者
LEUCUTA, SE
机构
[1] Faculty of Pharmacy, 3400, Cluj-Napoca
关键词
D O I
10.3109/02652049009021834
中图分类号
O69 [应用化学];
学科分类号
081704 ;
摘要
Nifedipine was embedded in a gelatin matrix to develop a prolonged release dosage form. The effects of polymer/drug ratio, size of the beads, cross-linking with formaldehyde and ethylcellulose coating of the gelatin microspheres on the in vitro release rate of the drug were investigated. The data were analysed according to different laws that can govern the release mechanism: first-order, Higuchi square root of time, spherical matrix and zero-order. The in vitro release kinetics of nifedipine from gelatin microspheres were mainly first-order; from formaldehyde hardened gelatin microspheres, complied with the diffusion model for a spherical matrix, and from ethylcellulose-coated gelatin microspheres, obeyed zero-order kinetics. These findings suggest the possibility of modifying the formulation in order to obtain the desired controlled release of the drug for a convenient oral sustained delivery system. The pharmacokinetic parameters of nifedipine, after adminstration of a single oral dose of nifedipine-loaded hardened gelatin microspheres to volunteers, suggest that the preparation can be considered as a sustained release delivery system for nifedipine. © 1990 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
引用
收藏
页码:209 / 217
页数:9
相关论文
共 18 条
  • [1] Aoki K., Sato K., Kawaguchi Y., Yamamoto M., Acute and long-term hypotensive effects and plasma concentrations of nifedipine in patients with essential hypertension, European Journal of Clinical Pharmacology, 23, pp. 197-201, (1982)
  • [2] Baker R.W., Lonsdale H.K., Tanquary A.C., Lacey R.E., Controlled Release of Biologically Active Agents, pp. 15-71, (1974)
  • [3] Benet L.Z., Ariens E.J., Drug Design, IV, pp. 1-35, (1973)
  • [4] Davis S.S., Illum L., McVie J.G., Tomlinson E., Microspheres and Drug Therapy. Pharmaceutical, Immunological and Medical Aspects, (1984)
  • [5] Echizen H., Eichelbaum M., Clinical pharmacokinetics of verapamil, nifedipine and diltiazem, Clinical Pharmacokinetics, 11, pp. 425-449, (1986)
  • [6] Goto S., Komatsu M., Tagawa K., Kawata M., Preparation and evaluation of gelatin microcapsules of sulfonamides, Chemical and Pharmaceutical Bulletin, 31, pp. 256-261, (1983)
  • [7] Gupta P.K., Hung C.T., Perrier D.G., Albumin microspheres. I. Release characteristics of adriamycin, International Journal of Pharmaceutics, 33, pp. 137-146, (1986)
  • [8] Higuchi T., Mechanism of sustained-action medication, Journal of Pharmaceutical Sciences, 52, pp. 1145-1149, (1963)
  • [9] Jakobsen P., Lederballe P.O., Mikkelsen E., Gas chromatographic determination of nifedipine and one of its metabolites using electron capture detection, Journal of Chromatography, 162, pp. 81-87, (1979)
  • [10] Jun H.W., Lai J.W., Preparation and in vitro dissolution tests of egg albumin microcapsules of nitrofurantoin, International Journal of Pharmaceutics, 16, pp. 65-77, (1983)