Experimental solubility profiling of marketed CNS drugs, exploring solubility limit of CNS discovery candidate.
We determined the experimental solubility of CNS marketed drugs. Of the 98 drugs measured, greater than 90% had solubility >10 μM in pH 7.4 buffer. Only seven drugs had solubility <10 μM. Using these data, we established a solubility criterion to support CNS discovery. The implication of poor solubility with potential safety concerns and undesirable side effects are discussed.
CNS Chemistry and DMPK Department, AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850-5437, USA. yun.alelyunas@astrazeneca.com
Yun W
YW
Alelyunas
James R
JR
Empfield
Dennis
D
McCarthy
Russell C
RC
Spreen
Khanh
K
Bui
Luciana
L
Pelosi-Kilby
Cindy
C
Shen
D002491:Central Nervous System Agents / Q000737:chemistry*; D004353:Drug Evaluation, Preclinical; D006863:Hydrogen-Ion Concentration; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012995:Solubility
D002491:Central Nervous System Agents; D004364:Pharmaceutical Preparations