An erodible association polymer system based on blends of cellulose acetate phthalate (CAP) and Pluronic F127, a block copolymer of poly(ethylene oxide) and poly(propylene oxide), has been investigated for its applicability to rate-programmed drug delivery. The compatibility and thermal properties were characterized by DSC and FTIR. Results from the thermal analysis indicate that the blends are compatible above 50% CAP, as revealed by a single composition-dependent glass transition temperature (Tg). The existence of molecular association through intermolecular hydrogen bonding between the carboxylic acid and the ether oxygen groups is supported by the observation of an upward shift in the IR carbonyl stretching frequency at increasing Pluronic F127 concentrations. Using theophylline as a model drug, the in vitro polymer erosion and drug release characteristics of the present polymer system were evaluated at different buffer pH's on a rotating-disk apparatus. The results show that the rates of both polymer erosion and drug release increase with the Pluronic F127 concentration in the blend. Further, at pH 4, the polymer erosion is minimal and the theophylline release appears to be governed mainly by diffusion through the polymer matrix. In contrast, at pH 7.4, the theophylline release is controlled primarily by the polymer surface erosion. To demonstrate the unique approach to programmed drug release based on the concept of non-uniform initial drug distribution, pulsatile patterns of drug release have been achieved successfully from the present surface-erodible polymer system using a multilaminate sample design with alternating drug-loaded layers. The results suggest that the pulsing frequency and peak rate of such pulsatile drug delivery are pH dependent; however, they can be modulated by varying the thickness, drug loading, and erosion rate of the constituent layers in the multilaminate.
cellulose acetate phthalate (CAP)Pluronic F127association polymerpulsatile drug deliveryprogrammable drug deliveryerodible polymer