VARIABLES THAT AFFECT THE MECHANISM OF DRUG-RELEASE FROM OSMOTIC PUMPS COATED WITH ACRYLATE METHACRYLATE COPOLYMER LATEXES

The feasibility of using modified Eudragit acrylic latexes as micropor ous coatings for osmotic devices was investigated. Potassium chloride tablets were coated with mixtures of Eudragit RS30D acid RL30D acrylic latexes that also contained a plasticizer (triethyl citrate or acetyl tributyl citrate) and a pore-forming agent(urea). A 2(5-1) fractional factorial experimental design was employed to determine the effect of five formulation variables (RS30D:RL30D polymer ratio plasticizer typ e, plasticizer level, urea level, and cure) on the in vitro release ra te of KCl in deionized water (di water), lag time, and coat burst stre ngth. The RS30D:RL30D polymer ratio had the greatest effect on the rel ease rate, and both lag time and burst strength were most affected by the urea level. Statistical optimization was performed, and a coat for mulation with predicted desirable in vitro performance was prepared an d tested. The in vitro release rate (di water), lag time, and coat bur st strength agreed well with the prediction. Dissolutions were also pe rformed in phosphate buffered saline (PBS; pH 7.4); several formulatio ns released markedly slower in PBS than in di water. This discrepancy was dependent on the type of plasticizer and the amount of pore former . Only those coat formulations containing acetyl tributyl citrate as t he plasticizer and a 100% urea [(g urea/g polymer solids) x 100] level exhibited similar release rates in di water and PBS. The mechanism of release from these devices was primarily osmotic, whereas the release from devices coated with a formulation containing triethyl citrate an d 50% urea was not dependent on the osmotic pressure difference. Devic es with an osmotic release mechanism behaved similarly in vivo and in vitro. Devices that were not osmotic released KCl at rates that were s ubstantially slower in PBS and in vivo than release rates in di water.