Characterization of hydrochlorothiazide and ß-cyclodextrin complexes in solid state

ONNAINTY R, MORA MJ, LONGHI MR, GRANERO GE

Congreso; 2º Reunión Internacional de Ciencias Farmacéuticas. RICifa 2010; 2012

Introduction Hydrochlorothiazide (HCT) is a diuretic class of thiazides. This drug is poorly soluble in water and slightly permeable through intestinal mucosa, therefore it belongs to IV group of the Biopharmaceutical Classification System1. To improve these drug unfavorable biopharmaceuticals properties, it was used like strategy the inclusion complex formation between HCT and b-cyclodextrin (b-CD). CDs have an exterior hydrophilic surface and a lipophilic central cavity. They are able to form inclusion complex with a big variety of molecules, both in solid state and aqueous solutions2. The encapsulation of the molecule affects its physicochemical properties, resulting in most of the studies cases, an improving of solubility and permeability through the biological membranes. Materials and methods Solid systems HCT:b-CD (1:1) were obtain by lyophilized and physic mixture of their components. Characterization of them was done by thermic analysis (DSC ? TG)3 and by infrared spectroscopy (FT-IR)4. Thermic profiles and FT-IR spectrums of the solid systems were compared with those of its pure components. Results It was observed from the DSC curve of the physic mixture between HCT and b-CD the corresponding peaks attributed to the dehydration of the b-CD and the fusion of the HCT. For the lyophilized system, it was obtained a thermogram ascribed to the presence of a new solid phase. This finding would be attributed to the inclusion of HCT in the hydrophobic cavity of the b-CD. FT-IR spectroscopy data suggests the formation of an inclusion complex between HCT and b-CD, because it was observed a shift in the frequency and a change in the shape of absorption bands of the functional groups of HCT. Instead, these changes did not be observed with the mixture physic of the HCT/b-CD system. Conclusion Obtained results from this study confirm the inclusion complex formation between HCT and b-CD, and suggest that the HCT is completely included in the CD hydrophobic cavity. References 1- Cudina O, Karljikovi-Raji K, Ruvarac-Bugarcic I, Jankovic I. Interaction of hydrochlorothiazide with cationic surfactant micelles of cetyltrimethylammonium bromide. Colloid Surface A 2005; 256, 225?232 2- Messner M, Kurkov SV, Jansook P, Loftsson T. Self-assembled cyclodextrin aggregates and nanoparticles. Int J Pharm 2010; 387, 199 -208. 3- Giordano F, Novak C, Moyano JR. Thermal analysis of cyclodextrins and their inclusión compounds. Thermochim Acta 2001, 380; 123 ? 151. 4- Salústio PJ, Feio G, Figueirinhas JL, Pinto JF, Cabral Marques HM. The influence of the preparation methods on the inclusion of model drugs in a b-cyclodextrin cavity. Eur J Pharm Biopharm 2009; 71, 377 -386.