The influence of polymer glass transition temperature and molecular weight on drug release from tablets containing poly(DL-lactic acid).
Five molecular weight grades of poly(DL-lactic acid) were characterized using gel permeation chromatography, differential scanning calorimetry, and viscometry to determine the effect of molecular weight on the glass transition temperature and the intrinsic viscosity. In addition, dynamic mechanical thermal analysis was used to assess the dynamic storage modulus and the damping factor of the polymer samples by detecting motional and structural transitions over a wide temperature range. Significant relationships were found between the molecular weight and these polymer properties. The five grades of poly(DL-lactic acid) were also incorporated as binders into matrix tablet formulations containing the model drug theophylline and microcrystalline cellulose. Dissolution studies showed significant correlations between the properties of the polymer and the matrix release profiles of the tablets. The release of theophylline slowed down progressively as the polymer molecular weight increased. The differences in release became less significant and reached a limiting asymptotic value as the molecular weight increased to 138,000. Further, tablet index testing was utilized to determine the compaction properties of the polymer granulations. Although there was no correlation with the molecular weight of PLA, brittle fracture index testing indicated very low brittleness for all granulations tested. However, bonding index determinations correlated very well with both the physical-mechanical properties of the polymer and drug release profiles.
Omelczuk
M O
MO
Drug Dynamics Institute, College of Pharmacy, University of Texas, Austin 78712-1074.
McGinity
J W
JW
D001696:Biomechanical Phenomena; D002152:Calorimetry, Differential Scanning; D002850:Chromatography, Gel; D003692:Delayed-Action Preparations; D007773:Lactates / Q000493:pharmacokinetics*; D019344:Lactic Acid; D008970:Molecular Weight; D010599:Pharmacokinetics; D011091:Polyesters; D011108:Polymers / Q000493:pharmacokinetics*; D012995:Solubility; D013607:Tablets; D013696:Temperature; D014783:Viscosity
D003692:Delayed-Action Preparations; D007773:Lactates; D011091:Polyesters; D011108:Polymers; D013607:Tablets; D019344:Lactic Acid; C033616:poly(lactide)