(717d) Effect of Acetate and Succinate Substitution Levels On Spray Dried Dispersions of Hypromellose Acetate Succinate – A Quality by Design Approach

Pharmaceutical pipelines are broadly hindered by poorly soluble compounds and a need exists to facilitate solubilization to enable the use of a greater number of drug candidates. To meet that need, hypromellose acetate succinate is frequently used to produce amorphous solid dispersions, typically by spray drying the polymer with a drug candidate, resulting in supersaturated levels of drug compounds in solution.  Currently, there are only three commercial grades of hypromellose acetate succinate available limiting the ability to tailor the drug release rate, supersaturation level and the extent to which recrystallization is prevented after drug release.

The present study utilizes a quality by design (QbD) hypromellose acetate succinate polymer set in which the acetate and succinate levels across the design space are varied. The samples in the QbD sample set are used to create spray dried dispersions with poorly soluble model drug compounds with varied physical properties. Evaluation of the performance parameters such as solubility enhancement, dissolution rate, and crystallization inhibition of the solid dispersions formed will be discussed. Furthermore, the advantages of utilizing a QbD approach to polymer substituent levels to tailor the performance of a drug candidate will be examined.