Estimation of drug precipitation upon dilution of pH-controlled formulations.
An equation is developed for estimating the precipitation that may occur upon diluting or injecting a (pH-)solubilized drug formulation. Since it is based on equilibrium, it is the worst case scenario for precipitation. This equation can be programmed in any commercially available spread sheet program such as Excel. According to the proposed equation, the type and the strength of the buffer species are the most significant factors that affect the pH and solubility of a drug in its microenvironment during dilution. To demonstrate the utility and robustness of the proposed equation, experimental measurements were performed using phenytoin as the model drug. The result suggests that the proposed equation can be used to indicate the possibility and the degree of precipitation that would occur upon injection. This provides a useful tool for the design of a successful pH-controlled solution formulation.
Narazaki
Ryuichi
R
College of Pharmacy, University of Arizona, 1703 East Mabel, Tucson, Arizona 85721-0207, USA.
Sanghvi
Ritesh
R
Yalkowsky
Samuel H
SH
D000927:Anticonvulsants / Q000008:administration & dosage / Q000737:chemistry; D002021:Buffers; D055598:Chemical Phenomena; D011232:Chemical Precipitation; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D006863:Hydrogen-Ion Concentration; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D010672:Phenytoin / Q000008:administration & dosage / Q000737:chemistry; D012995:Solubility
D000927:Anticonvulsants; D002021:Buffers; D004364:Pharmaceutical Preparations; D010672:Phenytoin