(640c) The Interaction of Solvent and Hypromellose Acetate Succinate Relate to Pharmaceutical Spray Dried Dispersion
- Conference: AIChE Annual Meeting
- Year: 2019
- Proceeding: 2019 AIChE Annual Meeting
- Group: Pharmaceutical Discovery, Development and Manufacturing Forum
Thursday, November 14, 2019 - 8:36am-8:54am
In this study, Dynamic Vapor Sorption (DVS-Resolution) was used to measure the methanol and acetone vapor sorption isotherms of the samples at 25 Â°C. HPMCAS was provided by The DuPont Nutrition & Health as AFFINISOLâ¢ HPMCAS and was used as received. Anhydrous reagent grade of acetone and methanol were used in DVS study. HPMCAS polymers of various grades were analyzed over a relative partial pressure (P/P0) range of 0-90%. The vapor program begins by exposing the sample to dry air to establish the dry mass. Then, the vapor concentration was increased in 10% P/Po steps to 90% P/Po followed by a final step at 95% P/Po. The vapor concentration is then decreased in a similar manner to accomplish a full sorption/desorption cycle. In-situ video images were collected at the end of each P/Po stage. Fickian, 1-D diffusion coefficients were determined at each step change in partial pressure. A spherical geometry was assumed for the particle shape and the EQPC d50 values were used as the average particle diameter. To make simple comparisons for the different vapors and samples, the diffusion values across the entire partial pressure range were averaged1.
It was found that HPMCAS 912G has the highest residual solvent after exposing to acetone and methanol up to a partial pressure of 95% even though HPMCAS 716G has highest equilibrium absorption content during the sorption process. The residual acetone in HPMCAS is significantly higher than the residual methanol in HPMCAS. To understand such behavior, various fitting models were used and diffusion coefficients were calculated. It appeared that the methanol vapor has higher diffusion coefficients compared to acetone vapor of the same sample. This can be explained by the higher affinity of acetone with acetate group than that of methanol. In comparing the three typical HPMCAS grades, diffusion rates for acetone are as follows: HPMCAS 126G > HPMCAS 716G > HPMCAS 912G, while the diffusion rates for methanol are as follows: HPMCAS 126G > HPMCAS 912G > HPMCAS 716G. This can also be explained by the higher affinity of acetone and methanol from higher concentration of acetate of HPMCAS. Analysis using various fitting model indicated that HPMCAS has a much stronger interaction with acetone than with methanol and water. The acetone content to saturate the monolayer is larger than that of methanol.
In conclusion, HPMCAS has higher acetone uptake and retention compared to methanol and water. The methanol vapor has higher diffusion coefficients compared to acetone vapor on the same grade of HPMCAS. The understanding of the interaction between organic solvent and HPMCAS excipients will help formulation scientist to improve spray dry dispersion process.