CIRCUMVENTION OF PH-DEPENDENT RELEASE FROM ETHYLCELLULOSE-COATED PELLETS

Aqueous latex dispersions of ethylcellulose are often used to form con trolled release coatings on pharmaceutical dosage forms. Occasionally, these products exhibit pH-dependent release characteristics, with rel ease rates typically being slow in water and dilute acid solutions and faster in solutions buffered to pH values near neutral. The source of this pH-dependent release is not obvious, since the principal mechani sm of release is by osmotic pumping, the coating polymer is neutral an d the effect is seen even with drugs that do not ionize within the pH range of interest. In this research, we used phenylpropanolamine HCl p ellets overcoated with ethylcellulose to investigate the source of pH dependency of release. pH dependency of release was observed in all ba tches plasticized with dibutylsebecate and column dried to an end-prod uct temperature of 43-5 degrees C. However, when batches were heated f or an additional 2 h in a forced air oven, or triethylcitrate was used as the plasticizer, release was virtually independent of pH. It was o bserved that heating the product above the T-g of the plasticized film was associated with more consistent release profiles. Contact angle m easurements suggested that these effects were associated with changes in surface behavior upon heating. Although titration experiments demon strated batch to batch variation in residual group content of ethylcel lulose, Little change in the titration data was seen after heating the ethylcellulose at 60 degrees C for 2 h. On the basis of these data, w e hypothesize that heating the product above the T-g of the plasticize d film results in film relaxation, enabling even distribution of the s urfactant throughout the film and thus minimizing the surface effects that are associated with pH-dependent release.