(588f) Spray Drying of Pharmaceuticals- Solubility and Diffusivity in the Acetone-Hpmcas System

Authors: 
Danner, R. P., Penn State Univ
Moser, J. D., Merck & Co., Inc.
In the pharmaceutical industry, one option to improve dissolution and kinetic solubility of poorly soluble active pharmaceutical ingredients (API) is to incorporate them into a soluble polymer matrix using spray drying. A key player in this process is, HPMCAS (hypromellose acetate succinate), a cellulose based polymer which has a high glass transition temperature and is used for trapping the API in its amorphous state. Throughout this process, there are different limitations that effect the rate of solvent removal from spray dried amorphous dispersions. The most limiting factor is the rate at which the diffusion occurs in the solvent-polymer system. Unlike liquid-liquid diffusion coefficients, liquid-polymer diffusion coefficients typically change over four orders of magnitude as the dispersion is dried. Without a basic understanding of this process, development and scale-up are empirical and costly. The solubility and diffusivity in the acetone-HPMCAS system have been experimentally determined using three experimental techniques: inverse gas chromatography, gravimetric sorption and differential pressure decay.  Below the effective glass transition temperature, the mutual diffusion behavior changes. The Vrentas-Duda free-volume theory has been extended to accurately capture this change in diffusive behavior in both infinite and finite concentration experiments.