Preparation and in vitro evaluation of gliclazide sustained-release matrix pellets: formulation and storage stability.

摘要

OBJECTIVE: Gliclazide-loaded matrix pellets consisting of ethylcellulose, microcrystalline cellulose (MCC), and sodium carboxymethyl starch were prepared by extrusion-spheronization. METHOD: To control the initial fast release of the matrix pellets, three coating methods were used: hot-melt coating, polymer aqueous dispersion film coating, and MCC powder coating. An orthogonal experiment (L(9)(3) (4) ) was applied to optimize the key process variables of MCC-powder coating. The in vitro dissolution profiles of the coating pellets were compared with the commercial tablets Diamicron(R) by the similarity factor (f (2)). The storage stability was measured to choose the best coating method. RESULT: Initial fast release was overcome by using the three coating methods. Rotation speed of friction plate and time of coating (addition of binder/coating agents) were both found to have the more important influence to drug release. The f (2) values between the three coated pellets and the commercial product were all greater than 50. The results of storage-stability tests suggest that the pellets prepared by MCC-powder-coating method are stable for at least 6 months under stress conditions (40 degrees C/75%RH), whereas the others failed. CONCLUSION: The MCC-powder-coating method offered the advantage of a one-step procedure compared with film coating and hot-melt coating.