INCLUSION COMPLEXATION OF BENZTHIAZIDE WITH CYCLODEXTRINS IN SOLUTION AND SOLID PHASE

Document Type : Original Article

Authors

Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, Egypt

Abstract

Investigations were made to prepare the inclusion compounds of Benzthiazide (BTZ) with b-cyclodextrin (b-CD), g-cyclodextrin (g-CD) and dimethyl-b-cyclodextrin (DMCD) in solid powdered form by the freeze-drying and the grinding methods.
The freeze drying and grinding methods were successful in obtaining the inclusion compounds of BTZ with the cyclodextrins (CDs). All the inclusion compounds obtained via freeze drying and grinding methods were in powdered form. It was shown by X-ray diffractometery that the inclusion compounds obtained by the two methods were amorphous. Clear differences in infrared (IR) absorption spectroscopy and differential scanning calorimetry were observed between the inclusion compounds and the physical mixtures of BTZ-CDs.
Furthermore, inclusion complexation of BTZ with g-CD, DMCD and b-CD in aqueous solutions were confirmed by the solubility method. The solubility curves of BTZ-g-CD and BTZ-DMCD were typical AL type curves while the solubility curve with b-CD can be classified as type Ap. The apparent stability constants, Kc, were calculated from the slope and intercept of the solubility diagrams 1110 M-1, 3053 M-1 and 1268 M-1 respectively. The dissolution rate of BTZ from the inclusion complexes was much more rapid than that of the BTZ alone. The enhanced dissolution rate may be due to the decrease in crystallinity and the increase in apparent solubility of the drug of the freeze-dried and ground samples, as expected from X-ray diffractometery and solubility study.