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 (<i>w</i>/<i>w</i>) ratio of hypromellose acetate succinate a...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/5/1281 |
| _version_ | 1797600950129524736 |
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| author | Stephen A. Thompson Daniel A. Davis Dave A. Miller Sandra U. Kucera Robert O. Williams |
| author_facet | Stephen A. Thompson Daniel A. Davis Dave A. Miller Sandra U. Kucera Robert O. Williams |
| author_sort | Stephen A. Thompson |
| collection | DOAJ |
| description | 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 (<i>w</i>/<i>w</i>) 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% <i>w</i>/<i>w</i> 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. |
| first_indexed | 2024-03-11T03:56:02Z |
| format | Article |
| id | doaj.art-b767cc7bb93447ea8ff20db29e18e865 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-11T03:56:02Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-b767cc7bb93447ea8ff20db29e18e8652023-11-18T00:34:41ZengMDPI AGBiomedicines2227-90592023-04-01115128110.3390/biomedicines11051281Pre-Processing a Polymer Blend into a Polymer Alloy by KinetiSol Enables Increased Ivacaftor Amorphous Solid Dispersion Drug Loading and DissolutionStephen A. Thompson0Daniel A. Davis1Dave A. Miller2Sandra U. Kucera3Robert O. Williams4Molecular Pharmaceutics and Drug Delivery Division, College of Pharmacy, The University of Texas at Austin, 2409 W. University Ave, PHR 4.214, Austin, TX 78712, USAAustinPx, LLC, 111 W Cooperative Way, Suite 300, Georgetown, TX 78626, USAAustinPx, LLC, 111 W Cooperative Way, Suite 300, Georgetown, TX 78626, USAAustinPx, LLC, 111 W Cooperative Way, Suite 300, Georgetown, TX 78626, USAMolecular Pharmaceutics and Drug Delivery Division, College of Pharmacy, The University of Texas at Austin, 2409 W. University Ave, PHR 4.214, Austin, TX 78712, USAThis 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 (<i>w</i>/<i>w</i>) 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% <i>w</i>/<i>w</i> 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.https://www.mdpi.com/2227-9059/11/5/1281ivacaftoramorphous solid dispersionpolymerpolymer alloydrug loadingKalydeco |
| spellingShingle | Stephen A. Thompson Daniel A. Davis Dave A. Miller Sandra U. Kucera Robert O. Williams Pre-Processing a Polymer Blend into a Polymer Alloy by KinetiSol Enables Increased Ivacaftor Amorphous Solid Dispersion Drug Loading and Dissolution Biomedicines ivacaftor amorphous solid dispersion polymer polymer alloy drug loading Kalydeco |
| title | Pre-Processing a Polymer Blend into a Polymer Alloy by KinetiSol Enables Increased Ivacaftor Amorphous Solid Dispersion Drug Loading and Dissolution |
| title_full | Pre-Processing a Polymer Blend into a Polymer Alloy by KinetiSol Enables Increased Ivacaftor Amorphous Solid Dispersion Drug Loading and Dissolution |
| title_fullStr | Pre-Processing a Polymer Blend into a Polymer Alloy by KinetiSol Enables Increased Ivacaftor Amorphous Solid Dispersion Drug Loading and Dissolution |
| title_full_unstemmed | Pre-Processing a Polymer Blend into a Polymer Alloy by KinetiSol Enables Increased Ivacaftor Amorphous Solid Dispersion Drug Loading and Dissolution |
| title_short | Pre-Processing a Polymer Blend into a Polymer Alloy by KinetiSol Enables Increased Ivacaftor Amorphous Solid Dispersion Drug Loading and Dissolution |
| title_sort | pre processing a polymer blend into a polymer alloy by kinetisol enables increased ivacaftor amorphous solid dispersion drug loading and dissolution |
| topic | ivacaftor amorphous solid dispersion polymer polymer alloy drug loading Kalydeco |
| url | https://www.mdpi.com/2227-9059/11/5/1281 |
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