Application of the Vrentas–Duda free‐volume theory of diffusion below the glass‐transition temperature: Application to hypromellose acetate succinate–solvent systems

Abstract

The Vrentas–Duda free‐volume theory for diffusion characterizes the diffusivity of a solvent in a polymer in terms of the concentration and size of the solvent, the temperature, and the glass transition temperature (Tg) of the individual components. The effective Tg of the polymer, however, is a function of the concentration of the solvent. This article introduces a modification that corrects for this change in the glass‐transition temperature, thus providing more accurate diffusivities. The model has been verified by comparison with experimental diffusivities of water, acetone, methanol, and tetrahydrofuran in hypromellose acetate succinate (HPMCAS). HPMCAS is widely used in the production of pharmaceutical formulations. One common application is the formation of amorphous solid dispersions with poorly soluble active pharmaceutical ingredients (APIs) for dissolution and solubility enhancement. Frequently, the APIs and HPMCAS are put into solution and spray dried at an outlet temperature below the normal glass‐transition temperature. The modified free‐volume theory is able to directly predict or correlate with only one adjustable parameter the diffusivities as a function of the concentration and temperature. © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47351.

Understanding Direct Powder Extrusion for Fabrication of 3D Printed Personalised Medicines: A Case Study for Nifedipine Minitablets

“…Unprocessed PEG 4000 also exhibited a sharp melting event at 59.2 ± 1.0 • C (Figure 4). The T g for HPMCAS was 123 • C, which is similar to previously reported values [19,20]. HPC did not exhibit any T g in the thermograms at the conditions tested, bearing in mind its low T g temperature, below 0 • C [21].…”

Solvent-Assisted Secondary Drying of Spray-Dried Polymers

“…The diffusion of solvents through amorphous polymers often follows Fickian diffusion, which is governed by the free volume in the system ( 16 ). In the three systems studied here, secondary drying is conducted at conditions deep in the glassy state—that is, more than 40°C below the wet T g of the polymer.…”

“…a single-solvent system), the size of free-volume pockets is as described in Sturm et al . ( 16 ) The model accounts for a decreasing diffusion coefficient as the sample becomes drier and less plasticized. In solvent-assisted drying, using water or methanol, the assisting solvent content stays constant throughout the secondary-drying process.…”

“…The kinetics of secondary drying are limited by two factors: (1) diffusion of solvent out of the solid particle ( 16 ) and (2) convection of solvent away from the solid particle. Convection and diffusion are coupled at the surface of the particle, where adequate convection drives the concentration gradient in the particle, enabling fast diffusion.…”

“…Vrentas and Duda pioneered the application of a free-volume theory of Fickian diffusion in amorphous polymers ( 17 , 18 ). Numerous subsequent studies by these authors and others have further developed these models and demonstrated methods to relate model parameters to experimental measurements ( 16 , 19 , 20 ). The model proposed in this study combines the approaches of Vrentas and Duda, as well as Sturm et al ( 16 ) and Schabel et al ( 21 ) to describe a ternary polymer-solvent-solvent system dried far below the glass-transition temperature (T g ) of the spray dried polymer, where T g changes with solvent concentration.…”