Consideration of drug load on the swelling kinetics of glassy gelatin matrices.

The effect of drug load on water transport into glassy gelatin beads and on the dynamic swelling behavior of the hydrated gel was studied through microscopic measurements of moving boundaries. Isoniazid was found to alter the glassy structure of gelatin, resulting in an increase in water penetration rates with a lowering of the apparent activation energy for water front movement. Differential scanning calorimetry studies revealed a decrease in the glass transition temperature with drug load, further indicating plasticization of the gelatin glass. The presence of drug also accelerated the outer swelling gelatin front, but, in contrast to the water front, the apparent activation energy for matrix expansion rose substantially with higher drug loads for temperatures greater than 20 degrees C. This observation may be rationalized as an increasing osmotic stress on the matrix induced by greater loading with hydrophilic drug. The osmotic stress, in turn, forces the gelatin matrix to expand outward, resulting in a higher apparent activation energy (Eact). Furthermore, the enhanced expansion was especially pronounced at higher temperatures where physical bonds, which are associated with gel structure and needed to resist swelling, are presumably weaker and fewer in number.