| Autor: |
Molly S. Adam, Warren K. Miller, Amanda M. Pluntze, Aaron M. Stewart, Jonathan L. Cape, Michael E. Grass, Michael M. Morgen |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
Pharmaceutics, Vol 14, Iss 3, p 555 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
1999-4923 |
| DOI: |
10.3390/pharmaceutics14030555 |
| Popis: |
Many active pharmaceutical ingredients (APIs) in the pharmaceutical pipeline require bioavailability enhancing formulations due to very low aqueous solubility. Although spray dried dispersions (SDDs) have demonstrated broad utility in enhancing the bioavailability of such APIs by trapping them in a high-energy amorphous form, many new chemical entities (NCEs) are poorly soluble not just in water, but in preferred organic spray drying solvents, e.g., methanol (MeOH) and acetone. Spraying poorly solvent soluble APIs from dilute solutions leads to low process throughput and small particles that challenge downstream processing. For APIs with basic pKa values, spray solvent solubility can be dramatically increased by using an acid to ionize the API. Specifically, we show that acetic acid can increase API solubility in MeOH:H2O by 10-fold for a weakly basic drug, gefitinib (GEF, pKa 7.2), by ionizing GEF to form the transient acetate salt. The acetic acid is removed during drying, resulting in a SDD of the original GEF free base having performance similar to SDDs sprayed from solvents without acetic acid. The increase in solvent solubility enables large scale manufacturing for these challenging APIs by significantly increasing the throughput and reducing the amount of solvent required. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
|
Nepřihlášeným uživatelům se plný text nezobrazuje |
K zobrazení výsledku je třeba se přihlásit.
|
