Solubilization of poorly soluble compounds using 2-pyrrolidone.
The solubilization of nine poorly soluble compounds in aqueous solution by 2-pyrrolidone has been studied. Solubility enhancement as high as 500-fold is achieved using 20% 2-pyrrolidone. A comparison shows that 2-pyrrolidone is a better solubilizer than glycerin, propylene glycol, polyethylene glycol 400 or ethanol. The observed solubilization curves are deconvoluted into components representing complexation and cosolvency. A clear linear relationship exists between the cosolvency solubilization power (sigma) of 2-pyrrolidone and the partition coefficient (log K(ow)) of the drug (R(2)=0.96) extending over three orders of magnitude. The stability constants for the formation of 1:1 complex (K(1:1)) involving 2-pyrrolidone and the drugs have been calculated. A weaker correlation (R(2)=0.74) is observed between the complexation constants and the partition coefficients of respective drugs. This study indicates that 2-pyrrolidone, like NMP, can act as a complexant at low concentrations and as a cosolvent at high concentrations and that both these properties are affected by the partition coefficient of the solute.
Jain
Parijat
P
Department of Pharmacy Practice and Science, College of Pharmacy, The University of Arizona, 1703 E. Mabel St., Tucson AZ 85721, USA. jainp@pharmacy.arizona.edu
Yalkowsky
Samuel H
SH
D000465:Algorithms; D002021:Buffers; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004573:Electrolytes; D000431:Ethanol; D005990:Glycerol; D006863:Hydrogen-Ion Concentration; D004364:Pharmaceutical Preparations / Q000737:chemistry; D011092:Polyethylene Glycols; D019946:Propylene Glycol; D011760:Pyrrolidinones / Q000737:chemistry*; D012995:Solubility; D012997:Solvents
D002021:Buffers; D004573:Electrolytes; D004364:Pharmaceutical Preparations; D011760:Pyrrolidinones; D012997:Solvents; D000431:Ethanol; D011092:Polyethylene Glycols; D019946:Propylene Glycol; C028537:2-pyrrolidone; D005990:Glycerol