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Pre-Processing a Polymer Blend into a Polymer Alloy by KinetiSol Enables Increased Ivacaftor Amorphous Solid
Stephen A Thompson1, Daniel A Davis2, Dave A Miller2
1Molecular Pharmaceutics and Drug Delivery Division, College of Pharmacy, The University of Texas at Austin, 2409 W. University Ave, PHR 4.214, Austin, TX 78712, USA.
Biomedicines
|May 27, 2023
Summary
Creating polymer alloys before amorphous solid dispersion (ASD) formulation enhances drug loading and dissolution. Pre-processing polymers into a single-phase alloy improved ivacaftor ASD performance compared to traditional blends.
Area of Science:
- Pharmaceutical Sciences
- Materials Science
Background:
- Amorphous solid dispersions (ASDs) are crucial for improving the bioavailability of poorly soluble drugs.
- Traditional ASD formulations often face limitations in drug loading and physical stability.
- Pre-processing polymers into alloys offers a novel approach to overcome these limitations.
Purpose of the Study:
- To investigate the impact of forming a single-phase polymer alloy on amorphous solid dispersion characteristics.
- To compare the performance of ASDs formulated with a polymer alloy versus a polymer blend.
- To evaluate drug loading, dissolution, stability, and molecular interactions.
Main Methods:
- KinetiSol compounding was used to create a hypromellose acetate succinate and povidone polymer alloy.
- Ivacaftor ASDs were prepared using the polymer alloy, unprocessed polymer blend, and individual polymers.
- Characterization included amorphicity, dissolution testing, Fourier transform infrared spectroscopy, and solid-state nuclear magnetic resonance.
Main Results:
- A higher drug loading of 50% (w/w) ivacaftor was achieved with the polymer alloy ASD compared to 40% for other compositions.
- The polymer alloy ASD exhibited a 33% greater dissolution concentration after 6 hours in simulated intestinal fluid.
- Altered hydrogen bonding between povidone and ivacaftor in the alloy explained the enhanced dissolution.
Conclusions:
- Forming a single-phase polymer alloy is a viable strategy to enhance ASD properties.
- Polymer alloy pre-processing allows for tailored material properties, improving drug loading, dissolution, and stability.
- This technique offers a promising route for developing advanced amorphous solid dispersions.
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