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Effect of Counterions on Dissolution of Amorphous Solid Dispersions Studied by Surface Area Normalized Dissolution
Yinshan Chen1, Joseph W Lubach1, Shijia Tang1
1Small Molecule Pharmaceutical Sciences, Genentech Inc., 1 DNA Way, South San Francisco, California 94080, United States.
Molecular Pharmaceutics
|August 2, 2021
Summary
Adding bases to amorphous solid dispersions (ASDs) significantly improves drug dissolution rates, especially at high drug loadings. This strategy enhances solubility for poorly water-soluble drugs, overcoming formulation limitations.
Area of Science:
- Pharmaceutical Sciences
- Drug Delivery
- Physical Chemistry
Background:
- Solubility enhancement is crucial for delivering poorly water-soluble drugs.
- Amorphous solid dispersions (ASDs) and salt formation are established strategies.
- Limitations exist, including phase separation in ASDs and stability requirements for salts.
Purpose of the Study:
- To investigate the effect of counterions on the dissolution performance of ASDs.
- To explore strategies for overcoming dissolution limitations in ASD formulations at high drug loadings.
Main Methods:
- Utilized intrinsic dissolution methodology for quantitative comparison, normalizing for particle size.
- Employed indomethacin (IMC)-poly(vinylpyrrolidone-co-vinyl acetate) ASD as a model system.
- Systematically studied the impact of incorporated bases, base-to-drug molar ratios, and drug loadings.
Main Results:
- Strong bases significantly enhanced indomethacin dissolution, while weak bases did not.
- Dissolution enhancement increased with higher base-to-drug molar ratios.
- Incorporating a strong base increased dissolution rate with increasing drug loading, unlike in base-free ASDs.
Conclusions:
- Ionization of the drug and increased microenvironment pH by bases are key to dissolution enhancement.
- This approach offers a promising method to overcome dissolution limitations in high-drug-loading ASD formulations.
- Counterion selection is a viable strategy for optimizing ASD dissolution performance.
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