Identifying the stable polymorph early in the drug discovery-development process.
The thermodynamically most stable polymorph under ambient conditions is almost without exception the most desirable crystalline form for development by a pharmaceutical company. It is, therefore, beneficial to discover and to characterize this polymorph at the earliest possible stage of development. A screen for discovering the stable polymorph of a pharmaceutical compound early in the drug discovery-development process is developed and described. In this screen, a small amount of compound is suspended in a diverse group of solvents for two weeks in an effort to crystallize the most stable polymorph. The solubility of the compound in each solvent utilized in the stable polymorph screen is also simultaneously determined using a simple gravimetric method. Ritonavir and an early development candidate (Pfizer compound A) are used as model compounds to demonstrate the utility of the screen for finding the stable polymorph early in the drug discovery-development process.
Miller
Jonathan M
JM
Pharmaceutical Research and Development, World Wide Pharmaceutical Sciences, Pfizer Global Research and Development, Ann Arbor Laboratories, Ann Arbor, Michigan 48105, USA. jonathan.miller@pfizer.com
Collman
Benjamin M
BM
Greene
Landon R
LR
Grant
David J W
DJ
Blackburn
Anthony C
AC
D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry; D015195:Drug Design; D007536:Isomerism; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D019999:Pharmaceutical Solutions; D019438:Ritonavir / Q000138:chemical synthesis / Q000737:chemistry; D012997:Solvents; D013059:Spectrum Analysis, Raman; D013816:Thermodynamics; D014961:X-Ray Diffraction
D019380:Anti-HIV Agents; D004364:Pharmaceutical Preparations; D019999:Pharmaceutical Solutions; D012997:Solvents; D019438:Ritonavir