MECHANISM OF RELEASE FROM PELLETS COATED WITH AN ETHYLCELLULOSE-BASED FILM

[摘要] Studies were conducted to determine the mechanism of drug release from pellets coated with an ethylcellulose-based pseudolatex widely accepted for use as a sustained release coating for pharmaceuticals. Possible mechanisms for release include solution/diffusion through the continuous polymer phase and/or plasticizer channels, diffusion through aqueous pores and osmotically driven release through aqueous pores. To distinguish between these mechanisms, the release rate was studied as a function of coating thickness, plasticizer content, and osmotic pressure in the dissolution medium. As the coating thickness was increased from 9 to 50-mu-m, the rate of release fell from 9.93.10(-3) to 1.71.10(-3) g phenylpropanolamine (PPA).HCl/100 ml h in an inversely proportional manner. Release as a function of plasticizer content was studied over the range 12 to 24% dibutyl sebacate (DBS). At 18 or 24% DBS, the rates of release of PPA.HCl were virtually identical, about 50% of PPA.HCl in six hours. At 12% DBS through, over 80% was released in the first hour. Surface area measurements and scanning electron microscopy (SEM) showed that the larger surface area of the 12% DBS batch was attributable to the presence of cracks in the coating. These results indicated that while the plasticizer is important in terms of forming a continuous film, diffusion through plasticizer channels is unlikely to make a significant contribution to the overall release rate. Release was also studied as a function of the osmotic pressure in the medium. A plot of release rate vs. osmotic pressure revealed an inverse linear relationship with a nonzero intercept. The steep dependency of release rate on osmotic pressure of the medium suggested that osmotically driven release is a major mechanism for release, while the nonzero intercept indicated some contribution from diffusion mechanisms. For all batches, SEM indicated that the film exhibited pores approximately 2-mu-m in diameter, consistent with these mechanisms. In summary, then, the release from PPA.HCl pellets coated with an ethylcellulose-based film appears to be a combination of osmotically driven release and diffusion through the polymer and/or aqueous pores. A mathematical expression for this type of release is presented.

[发布日期] 1990-12-01

[关键词] ETHYLCELLULOSE;FILM-COATING;MECHANISM OF RELEASE;PSEUDOLATEX COATING;OSMOTICALLY DRIVEN RELEASE