In Vitro Release of Theophylline from Poly(Lactic Acid) Sustained-Release Pellets Prepared by Direct Compression

Abstract

Poly(L-lactic acid), (L-PLA) pellets containing theophylline as a model drug were prepared with increasing bovine serum albumin (BSA) load of 10, 20, 30, 40, or 50% by direct compression. The drug release from pellets was studied in phosphate buffered saline (PBS, pH 7.4) at 37°C. The annealing effect on theophylline release from pellets was also studied at 20, 30, 60, and 80°C. In all cases, release kinetics followed the Higuchian mechanism with an initial burst effect followed by sustained release of theophylline during the experimental period. Increasing BSA load resulted in a linear increase in Higuchian release rates presumably because of the hydrophilic nature of BSA. Furthermore, BSA did not interact chemically with the polymer matrix and was held physically by the dense polymer matrix. However, drug release decreased with an increase in annealing temperature. Release of theophylline was higher from PLA-BSA combination pellets compared to PLA pellets at temperatures below the glass transition temperature (T_g) of the polymer and lower for temperatures above T_g The temperature effect on drug release may be attributed to both the reduction of core solubility in the bulk phase and the lowering of diffusibility of the polymeric membrane. No drug-polymer interactions or polymer degradation was observed within the experimental setup when studied by differential scanning calorimetry (DSC), infrared (FTIR) spectroscopy, and gravimetric methods. DSC studies of pellets showed no hints of microstructural changes (crystallinity) of the polymers. In our experiments, theophylline was released primarily by leaching through channels and not by polymer degradation. The release rate was dependent on BSA loading and annealing. It may be concluded that PLA pellets can be fabricated suitably using BSA and annealing to design sustained-release preparations of water-soluble drugs.