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Estimation of drug-polymer miscibility and solubility in amorphous solid dispersions using experimentally determined
Patrick J Marsac1, Tonglei Li, Lynne S Taylor
1Materials Characterization and Technology Assessment, Merck & Co., Inc., West Point, Pennsylvania 19486, USA.
Pharmaceutical Research
|September 10, 2008
Summary
Understanding drug-polymer miscibility is key for stable amorphous drug formulations. This study developed models to estimate mixing thermodynamics, aiding in predicting physical stability and preventing crystallization.
Area of Science:
- Pharmaceutical Sciences
- Materials Science
Background:
- Amorphous drug forms offer improved solubility and bioavailability but risk crystallization.
- Polymeric additives enhance physical stability of amorphous drug systems.
- Quantifying drug-polymer miscibility is crucial for optimized formulation design.
Purpose of the Study:
- Develop experimental models for quantitative thermodynamic estimates of amorphous drug-glassy polymer mixing.
- Investigate the thermodynamics of mixing amorphous drugs with amorphous polymers.
Main Methods:
- Coupled solution theory with experimental data to estimate thermodynamics of mixing.
- Utilized Flory-Huggins lattice theory for entropy of mixing estimation.
- Employed differential scanning calorimetry (DSC) for melting point depression and solubility studies in 1-ethyl-2-pyrrolidone to determine enthalpy of mixing.
Main Results:
- Observed varying degrees of melting point depression in miscible mixtures, with minimal depression in immiscible systems.
- Drug solubility in poly(vinylpyrrolidone) was generally found to be low.
- Calculated activity coefficients provided insights into free energy of mixing and drug solubility.
Conclusions:
- Combined solution theories with experimental data to assess drug-polymer miscibility.
- Provided a method to estimate physical stability of drug-polymer mixtures.
- Offered insights into the thermodynamic drivers of drug crystallization in polymeric systems.
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