Interaction of trimeprazine with cyclodextrins in aqueous solution

The synergistic effect of pH and complexation with cyclodextrins on some properties of phenothiazine derivative--trimeprazine (TM) was investigated. Inclusion complexes of TM with beta-cyclodextrin (beta-CD) and its substituted derivatives (DM-beta-CD, HP-beta-CD, beta-CDsulf) were obtained in phosphate buffer solution of different pH (6.8; 5.9; 5.0) using spectral and phase solubility methods Irrespective of the method of determination the apparent stability constant of TM-beta-CD system was the greatest and, in the case of the spectral method, its value increased with decreasing pH. The results obtained by the method of solubility diagrams indicate that increase in solubility of the basic form of TM, following decrease of pH, resulted rather from its transformation to a better soluble, protonated form than its inclusion into CD cavity. The thermodynamic parameters estimated from linear Van't Hoff plot suggest that the van der Waals forces were operating in the TM-beta-CD system. The effect of pH and the presence of cyclodextrins on photostability of TM was also investigated. The photochemical decomposition of TM in the absence and in the presence of CD proceeds according to the first order reaction. The charged form of TM was more stable than free base of this drug and hence the stability of TM increases first of all as result of a decrease in pH and then owing to the presence of CD. The data of 13C NMR analysis indicate that the aromatic portion of TM molecule tends to the interior of CD.