Pre-Processing a Polymer Blend into a Polymer Alloy by KinetiSol Enables Increased Ivacaftor Amorphous Solid Dispersion Drug Loading and Dissolution

This study compares the effects of pre-processing multiple polymers together to form a single-phase polymer alloy prior to amorphous solid dispersion formulation. KinetiSol compounding was used to pre-process a 1:1 (w/w) ratio of hypromellose acetate succinate and povidone to form a single-phase polymer alloy with unique properties. Ivacaftor amorphous solid dispersions comprising either a polymer, an unprocessed polymer blend, or the polymer alloy were processed by KinetiSol and examined for amorphicity, dissolution performance, physical stability, and molecular interactions. A polymer alloy ivacaftor solid dispersion with a drug loading of 50% w/w was feasible versus 40% for the other compositions. Dissolution in fasted simulated intestinal fluid revealed that the 40% ivacaftor polymer alloy solid dispersion reached a concentration of 595 µg/mL after 6 h, 33% greater than the equivalent polymer blend dispersion. Fourier transform infrared spectroscopy and solid-state nuclear magnetic resonance revealed changes in the ability of the povidone contained in the polymer alloy to hydrogen bond with the ivacaftor phenolic moiety, explaining the differences in the dissolution performance. This work demonstrates that the creation of polymer alloys from polymer blends is a promising technique that provides the ability to tailor properties of a polymer alloy to maximize the drug loading, dissolution performance, and stability of an ASD.

2.1. Materials

Ivacaftor was acquired from Nexconn Pharmatechs Ltd. (Shenzhen, China). Shin-Etsu Aqoat^® (Hypromellose Acetate Succinate) LMP were donated by Shin-Etsu, while Kollidon K30 (PVPK30) was donated by BASF Pharma. Biorelevant dissolution powder (FaSSIF/FeSSIF/FaSSGF) was obtained from Biorelevant Ltd. (London, UK). Sodium lauryl sulfate (SLS), NaCl, Na₂SO₄, microcrystalline cellulose, and croscarmellose were purchased from Fischer Scientific. Otherwise, ACS or equivalent grade chemicals were used. All compositions are weight by weight (w/w), unless otherwise specified.

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Thompson, S.A.; Davis, D.A., Jr.; Miller, D.A.; Kucera, S.U.; Williams, R.O., III. Pre-Processing a Polymer Blend into a Polymer Alloy by KinetiSol Enables Increased Ivacaftor Amorphous Solid Dispersion Drug Loading and Dissolution. Biomedicines 2023, 11, 1281. https://doi.org/10.3390/biomedicines11051281

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