Amorphous Solubility Advantage: Theoretical Considerations, Experimental Methods, and Contemporary Relevance
Abstract
Twenty-five years ago, Hancock and Parks asked a provocative question: “what is the true solubility advantage for amorphous pharmaceuticals?” Difficulties in determining the amorphous solubility have since been overcome due to significant advances in theoretical understanding and experimental methods. The amorphous solubility is now understood to be the concentration after the drug undergoes liquid-liquid or liquid-glass phase separation, forming a water-saturated drug-rich phase in metastable equilibrium with an aqueous phase containing molecularly dissolved drug.
While crystalline solubility is an essential parameter impacting the absorption of crystalline drug formulations, amorphous solubility is a vital factor for considering absorption from supersaturating formulations. However, the amorphous solubility of drugs is complex, especially in the presence of formulation additives and gastrointestinal components, and concentration-based measurements may not indicate the maximum drug thermodynamic activity.
This review discusses the concept of the amorphous solubility advantage, including a historical perspective, theoretical considerations, experimental methods for amorphous solubility measurement, and the contribution of supersaturation and amorphous solubility to drug absorption. Leveraging amorphous solubility and understanding the associated physicochemical principles can lead to more effective development strategies for poorly water-soluble drugs, ultimately benefiting therapeutic outcomes.
Read more here
Keisuke Ueda, Dana E. Moseson, Lynne S. Taylor, Amorphous Solubility Advantage: Theoretical Considerations, Experimental Methods, and Contemporary Relevance, Journal of Pharmaceutical Sciences, Volume 0, Issue 0, Publication History: Received July 12, 2024; Revised August 24, 2024; Accepted August 26, 2024; Published online August 31, 2024,DOI: 10.1016/j.xphs.2024.08.029, Also available on ScienceDirect, Copyright: © 2024 Published by Elsevier Inc. on behalf of American Pharmacists Association.
Read also our introduction article:
CPHI Milan 2024 – with a focus on excipients
