(759b) Impact of Hpmcas Polymer Properties On the in Vitro Performance of Spray Dried Dispersions – A Quality By Design Approach

Porter, W. III, The Dow Chemical Co.
Schmitt, R., The Dow Chemical Company
Petermann, O., Dow Wolf Cellulosics GMBH & CO. OHG
Guillaudeu, S., The Dow Chemical Company
Brackhagen, M., The Dow Chemical Company
Sprehe, M., The Dow Chemical Company

An increasing number of new drug entities suffer from low solubility making the development of a viable deliverable dose challenging. Hypromellose acetate succinate (HPMCAS) has proven effective at producing stable amorphous solid dispersions for poorly soluble active pharmaceutical compounds that demonstrate enhanced free drug levels in solution and inhibit recrystallization. Currently, there is a limited variety of HPMCAS product grades available, covering only a subspace of the compendial range. The limited coverage of the design space impedes the ability to understand how the HPMCAS properties influence the stability and performance of an amorphous dispersion. 

The present study examines the in vitro drug release rate and crystallization inhibition of amorphous spray dried dispersions formed with poorly soluble model APIs and HPMCAS polymers. HPMCAS polymers were varied in a Quality by Design approach to utilize the compendial range of acetate and succinate substitution levels and a range of molecular weights.

The effect of drug release rate and crystallization inhibition as a function of the HPMCAS acetate and succinate substitution levels in combination with the effect of the polymer molecular weight are evaluated for poorly soluble model compounds with varied physical properties.  Trends linking the physical properties of the model compounds with supersaturation and crystallization inhibition based on acetate and succinate levels and the molecular weight of the HPMCAS are evaluated.