Physicochemical properties of prostaglandin F2α (tromethamine salt): Solubility behavior, surface properties, and ionization constants
✍ Scribed by T. J. Roseman; S. H. Yalkowsky
- Publisher
- John Wiley and Sons
- Year
- 1973
- Tongue
- English
- Weight
- 620 KB
- Volume
- 62
- Category
- Article
- ISSN
- 0022-3549
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✦ Synopsis
The pH-solubility profile of the tromethamine salt of K F . b was determined. The intrinsic solubility of the free acid is 0.0042 M a t 25" and, as expected for a carboxylic acid, the solubility increased as a function of pH. However, at a pH value just above 5 , there is a marked increase in solubility, which is significantly greater than would be expected from the ionization constant of the acid. This type of bchavior is attributed to the formation of micelles that solubiliie the drug once a critical concentration and pH are reached. Independent determination of the critical micellar concentration (CMC) by drop volume or potentiometric techniques demonstrated that PGFk tromcthamine does form micellcs. The CMC increased with the degree of ionization and, therefore, is a function of pH. The pKa of I'C;F2, was determined by titration in aqueous media to be 4.90 -1 0.02. The pKa increased above the CMC as a function of concentration t o a maximum value of 5.6. When a plot ofconcentration cersus pKa is made, the point of deviation from the true value of 4.90 is in good agreement with the CMC reported by the drop volume technique. The interrelationship between the potentiometric, solubility. and surface properties of PGFk tromethamine are presented. Interestingly, these properties are qualitatively similar to those rcportcd for certain bile acids that have similar functional groups present on the parent cholanic acid nucleus. Keyphrdses 0 Prostaglandin F k , tromethamine salt--solubility behavior, surface properties, and ionization constants pH-sohbility protiles ~ prostaglandin Fk tromethamine salt, micelle formation [_7 Micelle formation--factor in solubilization of prostaglandin F2, trometham i nc salt 1 Model DMA 02/C. Anton Paar Kg.. A-8054. Graz. Austria.