Impact of the amount of excess solids on apparent solubility.
OBJECTIVE
The impact of excess solids on the apparent solubility is examined.


METHODS
The apparent solubility of some model drugs was measured in various buffered solutions, with various amounts of excess solid. To help understand the dependence of the solubility on the amount of solid, we evaluated the dissolution and crystallization rates of indomethacin (IDM), one of the model drugs, at near-equilibrium conditions.


RESULTS
In the case of IDM, the apparent solubility decreased with an increase in the solid amount at pH 5 and 6. On the other hand, it increased with an increase in the solid amount at pH 6.5 and 7. The crystallization and dissolution rates of IDM decreased and increased, respectively, with an increase in pH values, and became equal at between pH 6 and 7. Therefore, the apparent solubility was most likely to be affected by the balance between the crystallization and dissolution rates. The apparent solubility of other model drugs showed the same trend, although the dependency on the solid amount was not as significant as in the case of IDM.


CONCLUSIONS
The apparent solubility was affected by the amount of solid for all the model drugs investigated. This was most likely to be caused by a competition between the crystallization and dissolution rates.
Kawakami
Kohsaku
K
Developmental Research Laboratories, Shionogi & Co., Ltd., 12-4 Sagisu 5-chome, Fukushima-ku, Osaka 553-0002, Japan. kohsaku_kawakami@merck.com
Miyoshi
Kyoko
K
Ida
Yasuo
Y
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007213:Indomethacin / Q000737:chemistry*; D007700:Kinetics; D012995:Solubility; D012996:Solutions
D000894:Anti-Inflammatory Agents, Non-Steroidal; D012996:Solutions; D007213:Indomethacin