Physical-chemical characterization of binary systems of metformin hydrochloride with triacetyl-beta-cyclodextrin.
Interaction products of metformin hydrochloride (MF.HCl), an oral anti-hyperglycaemic agent highly soluble in water, with triacetyl-beta-cyclodextrin (TAbetaCyD), a hydrophobic CyD derivative practically insoluble in water, were prepared to evaluate their suitability for the development of a sustained-release dosage form of the drug. Equimolar MF.HCl-TAbetaCyD solid compounds were obtained by different techniques, i.e., physical mixing, kneading, co-grinding, sealed-heating, and spray-drying, in order to investigate and compare their effectiveness and influence on the physical-chemical properties of the final products. Differential scanning calorimetry, X-ray powder diffractometry, Fourier transform infrared spectroscopy and scanning electron microscopy were used for the solid-state characterization of the different MF.HCl-TAbetaCyD systems, whereas their in vitro dissolution properties were determined according to the dispersed amount method. According to the results of solid-state studies, the ability of the different preparation methods to promote effective interactions between drug and CyD varied in the order: spray-drying>co-grinding>kneading>sealed-heating approximately physical mixing. The same effectiveness rank order was observed also in dissolution studies. In fact the time to dissolve 100% drug varied increased from 1 min, for pure drug, to 3, 7, 40, 120 up to 420 min for physically mixed, sealed-heated, kneaded, co-ground and spray-dried products, respectively. Thus the drug-TA(CyD products obtained by spray drying and co-grinding were selected as the best candidates for the future development of a suitable prolonged-release oral dosage form of MF.HCl.
Corti
Giovanna
G
Department of Pharmaceutical Sciences, Faculty of Pharmacy, University of Florence, via U.Schiff 6, 50019 Sesto Fiorentino, Florence, Italy.
Capasso
Gaetano
G
Maestrelli
Francesca
F
Cirri
Marzia
M
Mura
Paola
P
D002152:Calorimetry, Differential Scanning; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D007004:Hypoglycemic Agents / Q000737:chemistry*; D008687:Metformin / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D012995:Solubility; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000737:chemistry*