Effect of Physicochemical Factors on the Release Kinetics of Hydrophilic Drugs from Poly(L-Lactic Acid) (L-PLA) Pellets

Abstract

Poly(L-lactic acid) (L-PLA) pellets intended for either parenteral or oral use were successfully prepared by a direct compression technique without the use of heat or organic solvents. Salicylic acid and theophylline were chosen as drug candidates. The drug release from pellets was affected by the compression pressure. The Higuchi plots of the drugs showed a t1/2 dependent drug release pattern. The release rates of these drugs from PLA pellets were directly correlated to their solubilities in the dissolution media. At lower pH (>7), the release of salicylic acid was found to be slower than theophylline; however, at higher pH (> 7), the release of salicylic acid was faster than that of the theophylline. The release rate of salicylic acid was higher at higher pHs, which was related to the increase in solubilities. Pellets were annealed at 20, 40, and 80°C. A lower release rate was observed with increasing temperatures. Above the glass transition temperature (Tg) of the polymer, the release of drugs was significantly decreased. The drug release was independent of the ionic strength of the media for both salicylic acid and theophylline. We showed earlier that no drug-polymer interactions or polymer degradation were observed when studied by differentials scanning calorimetry (DSC) and infrared spectroscopy (IR) (1). The release mechanism was primarily physical diffusion and leaching during the experimental period. We conclude that the release of low molecular weight (MW) drugs from the high MW L-PLA was independent of the pH and the ionic strength of the dissolution media, but was dependent on the polarity of the drug and formulation factors, such as compression pressure and annealing temperature.