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Investigation Of Dissolution Enhancement Of Itraconazole By Complexation With ?-And Hydroxy Propyl ?-Cyclodextrins

Author(s): K. P. R Chowdary, Shaik Srinivasa Rao

Complex formation of itraconazole (ITR) with β-cyclodextrin (βCD) and hydroxy propyl β-cyclodextrin (HPβCD) in aqueous solution and in solid state and the possibility of improving the solubility and dissolution rate of ITR via complexation with the above cyclodextrins were investigated. The phase solubility studies indicated the formation of a 1:1 M inclusion complex in solution with both βCD and HPβCD. The apparent stability constant (Kc) was 206.2 M-1 and 270.7 M-1 for βCD and HPβCD complexes, respectively. Differential Scanning Calorimetry (DSC) studies indicated the formation of solid inclusion complexes of ITR-βCD and ITR-HPβCD at 1:4 ratio only. Solid complexes of ITR-βCD and ITR-HPβCD (1:l and 1:2 M) prepared by kneading and coevaporation methods exhibited higher rates of dissolution and dissolution efficiency values than the corresponding physical mixtures and ITR itself. Higher dissolution rates were observed with kneaded complexes than with those prepared by coevaporation. Increases of 23.4 and 83.4-fold in the dissolution rate were observed respectively with ITR-βCD (1: 2 M) and ITR-HPβCD (1:2 M) kneaded complexes.


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