Improved amorphous solid dispersion performance using binary polymer combinations

Tian Xie, Purdue University


With increasing attrition rate of new molecular entities due to sub-optimum aqueous solubility, formulation strategies that could improve the dissolution rate and apparent solution concentration are of current interest. Amorphous solid dispersions are attractive over other enabling technologies since they are supersaturating solid dosage forms. However, crystallization may occur during storage as well as during dissolution of ASDs, negating the solubility advantage. Unfortunately, choosing the optimum pharmaceutically acceptable polymeric inhibitor for each of these crystallization pathways is largely empirical. The best polymer for inhibiting solid state crystallization may be ineffective in preventing crystallization during dissolution. Moreover, the release rate of the drug from the ASDs depend on both the type and the amount of the polymer in the formulation. Therefore, an important advance in solid dispersion formulation could be to incorporate combinations of polymers to tailor release profiles, while providing optimized crystallization inhibition. This will expand the application of solid dispersions based on a rational formulation approach that includes both solid state and solution performance characteristics, and provide greater confidence in the use of solid dispersion strategies.




Taylor, Purdue University.

Subject Area

Pharmacy sciences

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