Preparation of nimodipine microspheres contained in a solid dispersion by the emulsion-solvent-diffusion method and evaluation of their in vitro and in vivo characteristics
Fude Cui1*; Xiujuan Pang1; Mingshi Yang1; Xu Wang1; Y. Kawashima2
1Shenyang Pharmaceutical University, Shenyang, China 2School of Pharmaceutical Sciences, Aichi Gakuin University, Japan
Abstract Purpose: Nimodipine, as a water insoluble model drug, was formulated into immediate and sustained release microspheres in a solid dispersion by the emulsion-solvent-diffusion method in a single step. Methods: Special attention was devoted to improving the dissolution rate of the drug and then the controlled release of drug from the microspheres. Eu E100 and Aerosil were employed as a solid dispersion base for the immediate release microspheres, while HP55 and Aerosil were employed as a solid dispersion base for the sustained release microspheres, while ethyl cellulose (EC) was selected as a retarding agent to control the drug release rate. Micromeritic properties of the microspheres, the drug dispersion state and the drug release profiles of the microspheres were investigated. Relative bioavailabilities of two types of microspheres were compared with NimotopTM, a commercial nimodipine tablet, in a study in 3 healthy dogs. Results: Two types of microspheres i.e. immediate release and sustained release microspheres could be successfully prepared through adjustment of the ratio of nimodipine to the functional additives. The particle size of the resultant microspheres was mainly controlled by the agitation speed during the manufacturing process. Following X-ray, DTA and SEM analysis, it was found that nimodipine was highly dispersed and present in the microspheres in an amorphous state. The drug release rate from the microspheres was very dependent on the type and amount of the functional additives in the formulation. The relative bioavailabilities of the immediate release microspheres and sustained release microspheres, compared with the NimotopTM tablet, were 118.2 % and 96.1 %, respectively. Conclusions: The emulsion-solvent-diffusion method is a simple and efficient technique for designing functional microspheres for poorly water-soluble drugs.
Fude Cui,
Xiujuan Pang,
Mingshi Yang etc
.Preparation of nimodipine microspheres contained in a solid dispersion by the emulsion-solvent-diffusion method and evaluation of their in vitro and in vivo characteristics[J] AJPS, 2006,V1(1): 1-6
2006, Vol. 1 