(640c) The Interaction of Solvent and Hypromellose Acetate Succinate Relate to Pharmaceutical Spray Dried Dispersion

An increasing number of new chemical entities suffer from poor solubility in aqueous media making drug delivery via oral solid dosage form challenging. To address this issue, formulations are increasingly relying on the use of amorphous solid dispersions of the active with an excipient. The excipient serves the function of stabilizing the active as amorphous in the solid state and acts as a nucleation inhibitor upon dissolution. The use of spray drying is one of the leading technologies for this application space. Similarly, hypromellose acetate succinate (HPMCAS) is one of the leading excipients used in spray drying. Although extensively used in spray drying, little is understood about the affinity of organic solvents for the HPMCAS polymer. The affinity of the spray solvent for HPMCAS can impact drying rate, secondary drying rate (removal of residual solvent in a secondary batch process), and the glass transition temperature of the spray dried dispersion. The objective of this study was to understand the desorption/adsorption of organic solvents to HPMCAS.

In this study, Dynamic Vapor Sorption (DVS-Resolution) was used to measure the methanol and acetone vapor sorption isotherms of the samples at 25 °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.

References

1. Dynamic Vapour Sorption for Organic Solvent Sorption by Surface Measurement Systems. https://azom.com/article.aspx?ArticleID=5181