Roles of Supersaturation and Liquid–Liquid Phase Separation for Enhanced Oral Absorption of Poorly Soluble Drugs from Amorphous Solid Dispersions
Amorphous solid dispersion (ASD) is one of the most important enabling formulation technologies for the development of poorly soluble drugs. Because of its thermodynamically unstable nature in both solid and wet states, the evaluation and optimization of the formulation performance involves some dif...
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MDPI AG
2025-02-01
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| author | Kohsaku Kawakami |
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| author_sort | Kohsaku Kawakami |
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| description | Amorphous solid dispersion (ASD) is one of the most important enabling formulation technologies for the development of poorly soluble drugs. Because of its thermodynamically unstable nature in both solid and wet states, the evaluation and optimization of the formulation performance involves some difficulties. The dissolution process is sensitively influenced by various factors, including the applied dose, medium composition, and pH. Supersaturated solutions can cause liquid–liquid phase separation (LLPS) and/or crystallization, which complicates the comprehension of the dissolution process. However, LLPS should be evaluated carefully because it is closely related to oral absorption. As LLPS concentration is analogous to amorphous solubility, it can be a key factor in predicting oral absorption from ASDs, if absorption is limited by solubility. Moreover, LLPS droplets are expected to increase transmembrane flux by increasing the drug concentration near the epithelial cell membrane. In this review, recently updated knowledge on the dissolution, membrane permeation, and oral absorption behaviors of ASDs is discussed with an emphasis on LLPS behavior. |
| format | Article |
| id | doaj-art-97eeb0c29dd24d6bb3d27781d452ac19 |
| institution | DOAJ |
| issn | 1999-4923 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | MDPI AG |
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| series | Pharmaceutics |
| spelling | doaj-art-97eeb0c29dd24d6bb3d27781d452ac192025-08-20T02:44:54ZengMDPI AGPharmaceutics1999-49232025-02-0117226210.3390/pharmaceutics17020262Roles of Supersaturation and Liquid–Liquid Phase Separation for Enhanced Oral Absorption of Poorly Soluble Drugs from Amorphous Solid DispersionsKohsaku Kawakami0Research Center for Macromolecules and Biomaterials, National Institute for Materials Science, 1-1 Namiki, Tsukuba 305-0044, Ibaraki, JapanAmorphous solid dispersion (ASD) is one of the most important enabling formulation technologies for the development of poorly soluble drugs. Because of its thermodynamically unstable nature in both solid and wet states, the evaluation and optimization of the formulation performance involves some difficulties. The dissolution process is sensitively influenced by various factors, including the applied dose, medium composition, and pH. Supersaturated solutions can cause liquid–liquid phase separation (LLPS) and/or crystallization, which complicates the comprehension of the dissolution process. However, LLPS should be evaluated carefully because it is closely related to oral absorption. As LLPS concentration is analogous to amorphous solubility, it can be a key factor in predicting oral absorption from ASDs, if absorption is limited by solubility. Moreover, LLPS droplets are expected to increase transmembrane flux by increasing the drug concentration near the epithelial cell membrane. In this review, recently updated knowledge on the dissolution, membrane permeation, and oral absorption behaviors of ASDs is discussed with an emphasis on LLPS behavior.https://www.mdpi.com/1999-4923/17/2/262amorphous solid dispersioncrystallizationsupersaturationliquid–liquid phase separationmembrane permeabilityoral absorption |
| spellingShingle | Kohsaku Kawakami Roles of Supersaturation and Liquid–Liquid Phase Separation for Enhanced Oral Absorption of Poorly Soluble Drugs from Amorphous Solid Dispersions Pharmaceutics amorphous solid dispersion crystallization supersaturation liquid–liquid phase separation membrane permeability oral absorption |
| title | Roles of Supersaturation and Liquid–Liquid Phase Separation for Enhanced Oral Absorption of Poorly Soluble Drugs from Amorphous Solid Dispersions |
| title_full | Roles of Supersaturation and Liquid–Liquid Phase Separation for Enhanced Oral Absorption of Poorly Soluble Drugs from Amorphous Solid Dispersions |
| title_fullStr | Roles of Supersaturation and Liquid–Liquid Phase Separation for Enhanced Oral Absorption of Poorly Soluble Drugs from Amorphous Solid Dispersions |
| title_full_unstemmed | Roles of Supersaturation and Liquid–Liquid Phase Separation for Enhanced Oral Absorption of Poorly Soluble Drugs from Amorphous Solid Dispersions |
| title_short | Roles of Supersaturation and Liquid–Liquid Phase Separation for Enhanced Oral Absorption of Poorly Soluble Drugs from Amorphous Solid Dispersions |
| title_sort | roles of supersaturation and liquid liquid phase separation for enhanced oral absorption of poorly soluble drugs from amorphous solid dispersions |
| topic | amorphous solid dispersion crystallization supersaturation liquid–liquid phase separation membrane permeability oral absorption |
| url | https://www.mdpi.com/1999-4923/17/2/262 |
| work_keys_str_mv | AT kohsakukawakami rolesofsupersaturationandliquidliquidphaseseparationforenhancedoralabsorptionofpoorlysolubledrugsfromamorphoussoliddispersions |