Complexation of moricizine with nicotinamide and evaluation of the complexation constants by various methods.
The solubility of the antiarrhythmic drug moricizine at physiologic pH is very low. Precipitation after rapid intravenous injection of the hydrochloride salt of moricizine could be a concern. The enhancement of solubility of moricizine near physiologic pH via complexation with nicotinamide was examined as a potential solubilization technique. The studies were performed in pH 6 and pH 7 phosphate buffers at 25 degrees C by the phase solubility method. Moricizine formed 1:1 and 1:2 complexes with nicotinamide at pHs of 6 and 7. The complexation constants K1:1 and K1:2 were estimated by a previously described scheme and equation and compared with those obtained by fitting a line and a parabola to the equations derived from the scheme for both the approximate and exact solutions. The data were best represented by a parabolic regression analysis of the exact solution of the derived equation with values for K1:1 and K1:2 at pH 6 of 16.60 and 0.93 M-1, respectively, and at pH 7 of 7.70 and 5.41 M-1, respectively.
Hussain
M A
MA
DuPont Merck Pharmaceutical Company, Pharmacy R&D, Wilmington, DE 19880-0400.
DiLuccio
R C
RC
Maurin
M B
MB
D002851:Chromatography, High Pressure Liquid; D006863:Hydrogen-Ion Concentration; D016293:Moricizine / Q000737:chemistry*; D009536:Niacinamide / Q000737:chemistry*; D012044:Regression Analysis
D009536:Niacinamide; D016293:Moricizine