Effect of three types of additives in poor solvent on preparation of sustained-release nitrendipine microspheres by the quasi-emulsion solvent diffusion method

Sustained-release microspheres of nitrendipine with hydroxypropylmethylcellulose phthalate (HP-55) having a solid dispersion structure were prepared by using the quasi-emulsion solvent diffusion method of the spherical crystallization technique. To investigate the effect of the additives in poor solvent on the preparation of the nitrendipine microspheres, three types of additives, i.e. C12H25,NaO4S (sodium dodecyl sulfate), NaOH, and KH2PO4NaOH mixture, were chosen. The resultant microspheres were evaluated with respect to their recoveries, micromeritic properties and release rates. The mechanisms involved in the effect of different poor solvents on formation of the microspheres are discussed. The sustained-release nitrendipine microspheres could not be prepared without using any additives added to the poor solvent. The additives dissolved in poor solvent could affect the micromeritic properties and the release profiles of the resultant microspheres. On increasing the amount of additives, the total recoveries of microspheres were increased and the average diameter of the microspheres was reduced. It was found that a dissociation of HP-55 in poor solvent contributed to the formation of sustained-release nitrendipine microspheres. The release rate of the microspheres prepared with sodium dodecyl sulfate aqueous solution was slower than that of the other two additives, due to the more dense structure formed. Since HP-55, a pH-dependent polymer, was formulated in the present microspheres, the pH value of dissolution medium was one of critical factors to determine the dissolution rate.