title: Complexation of moricizine with nicotinamide and evaluation of the complexation constants by various methods.
abstract: 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.
authors.affiliation: DuPont Merck Pharmaceutical Company, Pharmacy R&D, Wilmington, DE 19880-0400.
authors.forename: M A
authors.initials: MA
authors.lastname: Hussain
authors.forename: R C
authors.initials: RC
authors.lastname: DiLuccio
authors.forename: M B
authors.initials: MB
authors.lastname: Maurin
mesh_terms: D002851:Chromatography, High Pressure Liquid; D006863:Hydrogen-Ion Concentration; D016293:Moricizine / Q000737:chemistry*; D009536:Niacinamide / Q000737:chemistry*; D012044:Regression Analysis
chemical_list: D009536:Niacinamide; D016293:Moricizine