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Molecular Entanglement and Electrospinnability of Biopolymers
Published on: September 3, 2014
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Drug-Polymer Miscibility and the Overlap Concentration (C*) as Measured by Rheology: Variation of Polymer Structure.
Anasuya Sahoo1, Ronald A Siegel2,3
1Department of Pharmaceutics, 9-177 WDH, University of Minnesota, 308 Harvard Street S.E, Minneapolis, MN, 55455, USA.
Pharmaceutical Research
|August 8, 2023
Summary
Amorphous solid dispersions (ASDs) prevent drug crystallization when polymer concentration exceeds overlap concentration (C*). This finding aids in designing stable drug formulations for improved bioavailability.
Area of Science:
- Materials Science
- Pharmaceutical Sciences
- Physical Chemistry
Background:
- Amorphous solid dispersions (ASDs) enhance oral bioavailability of poorly soluble drugs by molecularly dispersing them in a polymer matrix.
- High polymer concentrations are traditionally used to prevent drug crystallization in ASDs.
- Recent findings suggest the overlap concentration (C*) is the critical polymer concentration for maintaining drug amorphous state.
Purpose of the Study:
- To assess the solid-state stability of ASDs formulated with diverse polymers and drugs at varying concentrations (C) and molecular weights (MWs).
- To test the hypothesis that drug crystallization decreases with increasing C/C* and is eliminated when C > C*.
- To investigate the dependence of C* on polymer MW and drug-polymer interaction strength.
Main Methods:
- Formulation of ASDs with ketoconazole and felodipine using various polymers like poly(vinylpyrrolidone) (PVP), polyacrylic acid, and their copolymers.
- Rheological determination of overlap concentration (C*) for polymers in molten drug.
- Assessment of drug crystallization via measurement of enthalpy of fusion (ΔHf) and X-ray diffraction.
Main Results:
- Confirmed that the degree of drug crystallization is a function of the ratio of polymer concentration to overlap concentration (C/C*).
- Observed essentially no drug crystallization when the polymer concentration exceeded the overlap concentration (C > C*).
- Demonstrated that C* is dependent on polymer molecular weight and drug-polymer interactions.
Conclusions:
- The findings provide guidance for selecting appropriate polymers to inhibit drug crystallization in ASDs.
- The overlap concentration (C*), determined rheologically, can be utilized to compare drug-polymer interactions for polymers of similar MW.
- This research advances the rational design of stable and bioavailable amorphous solid dispersions.
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