Design of sustained-release nitrendipine microspheres having solid dispersion structure by quasi-emulsion solvent diffusion method

Abstract

To improve the bioavailability of nitrendipine microspheres, a sustained-release microspheres having solid dispersion structure were prepared in one step. Two types of polymer, i.e. solid dispersing and sustained-release polymers, were employed to prepare the microspheres by the spherical crystallization technique, i.e. quasi-emulsion solvent diffusion method. The factors of effect on micromeritic properties and release profiles of the resultant microspheres were investigated. And the bioavailability of nitrendipine microspheres was evaluated in six healthy dogs. The results showed that the particle size of microspheres was determined mainly by the agitation speed. The dissolution rate of nitrendipine from microspheres was enhanced significantly with increasing the amount of dispersing agents, and sustained by adding retarding agents. The release rate of microspheres could be controlled as desired by adjusting the combination ratio of dispersing agents to retarding agents. The results of X-ray diffraction and differential scanning calorimetry analysis indicated that the crystalline form of nitrendipine was disordered, suggesting that nitrendipine was highly dispersed in microspheres, so as amorphous state. The release profiles and content of the microspheres stored at a temperature of 40°C and a relative humidity of 75% were unchanged during 3 months of accelerating condition of storage. And the relative bioavailability of the sustained-release microspheres compared with the Baypress™ tablets and the conventional tablets was 107.78% and 309.82%. In conclusion, the sustained-release microspheres with solid dispersion structure improved the bioavailability of the water insoluble drug and prolonged the T max value.