The Cyclodextrins as Modelling Agents of Drug Controlled Release

摘要

The controlled release of nicardipine (NC) was achieved by hybridizing its hydrophilic and hydrophobic cyclodextrin (CDs) complexes, i.e., those with hydroxypropyl-ß-cyclodextrin (HPßCD) andtriacetyl-ß-cyclodextrin (TAßCD),respectively. 1H-nuclearmagnetic resonance (1H-NMR) was performed to examine the interaction between both CDs and NC in solution. The solid complexes of NC : HPßCD and NC : TAßCD were prepared, in a 1 : 1 molar ratio by the spray-drying method. Complexation in the solid state was demonstrated by differential scanning calorimetry (DSC) and powder X-ray diffractometry. In vitro dissolution studies were carried out in simulated gastric (pH 1.2) and intestinal (pH 6.8) fluids, according to the USP basket method. The 1H-NMR studies provided clear evidence of an interaction between the CDs and the aromatic rings of NC. The DSC thermograms of the solid complexes showed no endothermic peak due to NC melting and their diffraction pattern was completely diffuse, which suggested the formation of a novel type solid phase with an amorphous character. The low dissolution rate of NC, a weak basic drug, in alkaline medium was significantly improved by complexation with HPßCD. In contrast, the in vitro release of this drug from the NC : TAßCD complexes was markedly retarded in both dissolution media. An optimal formulation was then designed by the combination, in different molar ratios, of these two complexes. The release behavior of these preparations was investigated and it was observed that the retarding effect was dependent on the amount of the NC : TAßCD complex. In addition, the initial release rate became faster as the molar ratio of the NC : HPßCD complex increased.