Application of polyvinyl acetate aqueous dispersion in preparation of sustained release matrices by spray drying process

Abstract

An application of polyvinyl acetate (PVAc) aqueous dispersion in preparation of sustained release matrices via spray drying technique was investigated. Three different water soluble drugs, diltiazem hydrochloride, theophylline and furosemide, were employed as model drugs. The physical properties of spray dried drug-PVAc powders were evaluated. Spray dried theophylline-PVAc powders (T-PVAc) was more spherical than furosemide-PVAc (F-PVAc) and diltiazem hydrochloride-PVAc powders (D-PVAc). Therefore, the T-PVAc powders possessed better flow characteristics than the others. All spray dried drug-PVAc powders had narrow size distribution. In addition, X-ray diffractogram revealed that diltiazem hydrochloride and furosemide existed in an amorphous state after spray drying with PVAc, while theophylline anhydrous seemed to be in both crystalline and amorphous state. In addition, the X-ray patterns of T-PVAc powders displayed the polymorphic change of theophylline from a theophylline anhydrous form II to a theophylline anhydrous form I. Thermal analysis and infrared spectroscopy studies revealed that theophylline and diltiazem hydrochloride did not react chemically with PVAc and additives. However, F-PVAc powders showed some change in spectrum. Spray dried drug-PVAc powders were easily compressed directly into the matrices. The release profile studies indicated that diltiazem hydrochloride matrix tablet had a faster release rate than theophylline and furosemide matrix tablet, respectively. Water solubility of drugs, amount of polymer and pH of the dissolution medium were important factors in the controlling the release of matrix tablet. However, the different compression force did not play an effect on drug release. The drug release kinetic of the PVAc matrices could be explained by Higuchi's equation, but at low polymer content, both diffusion and erosion controlled the drug release from the PVAc matrices. In conclusion, polyvinyl acetate aqueous dispersion wasapplied well in conjunction with spray drying technique to produce sustained release matrix.