Effect of cyclodextrin complexation on aqueous solubility and photostability of phenothiazine

The effect of cyclodextrin (beta-CD, gamma-CD and substituted beta-CD derivatives) complexation on the solubility and photostability of phenothiazine (Ph) was compared. The phase solubility method was applied to calculate the stability constants of soluble 1:1 or 1:2 inclusion compounds formed between Ph and CDs. Photochemical decomposition in solution of phenothiazine alone and in the presence of beta-CD or beta-CD derivatives, was found to proceed according to the two stage first-order reaction and in the case of gamma-CD, in a single stage reaction. Formation of solid inclusion complexes of Ph with CDs was evaluated using IR, 13C NMR and DSC studies. The influence of the complexation technique in the solid state (kneading, heating and freeze-drying) on the solubility of Ph was compared. It was establish that the improvement in solubility and stability of Ph was dependent on the kind of CD. When the complexation proceeded in solution it was more effective.