An investigation of the chemical, physical-mechanical, and dissolution properties of controlled release tablets containing poly(d,l-lactic acid)

Studies were designed to obtain a fundamental understanding of how the chemical and physical-mechanical properties of poly(d,l-lactic acid) (PLA) influenced the dissolution properties of matrix tablets utilizing PLA as a retardant polymer. Gel permeation chromatography, differential scanning calorimetry, capillary viscometry, and dynamic mechanical thermal analysis were used to study the effect of molecular weight on the glass transition temperature (Tg), viscosity, modulus and damping factor of five molecular weight grades of PLA. Significant relationships based on theoretical polymer principles were found to occur between the molecular weight and these properties.; A wet granulation process was used to incorporate the PLA into matrix tablet formulations containing the model drug theophylline, both as an organic binder and an aqueous dispersion. Results of dissolution studies showed that the drug release slowed down to an asymptotic limit as the molecular weight of the PLA increased. This effect was in turn based on the relationship between the molecular weight, Tg, and modulus of the polymer. The results of tablet index testing demonstrated that there was a significant correlation between the bonding index and the molecular weight of the polymer, as well as the drug release during dissolution. Furthermore, dissolution studies showed that the drug release was dependent on the polymer concentration, as well as the level and nature of the excipient. Overall, the results of these studies were integral components in assessing the mechanism of drug release.; The effect of thermal treatment on the compaction properties and mechanism of drug release were investigated. Tablet thermal treatment, above the Tg of the polymer, had a significant influence on increasing the bonding index and further retarding the drug release in certain cases. In addition, although thermal treatment had increased the porosity and reduced the residual moisture of the formulation, it had no impact on the Tg and molecular weight of the PLA.; The incorporation of an aqueous dispersion of PLA was found to significantly improve the bonding properties, and retard the drug release of tablets containing a poorly compactable drug, such as acetaminophen. Studies were also undertaken which demonstrated that the dissolution and compaction properties of tablets utilizing an aqueous dispersion of PLA were equivalent and in some cases, superior to formulations utilizing commercial dispersions of other polymers.