Improved Dissolution Rate of Leflunomide using Hydroxypropyl-β-Cyclodextrin Inclusion Complexation by Freeze-Drying Method

preeti vidhyadhar bankar, Omprakash P. Mahatma


Inclusion complexes between leflunomide, a poorly water soluble antirheumatic drug, and HP-β-cyclodextrin (HP-β-CD) were used to improve the solubility and dissolution rate of the drug. Leflunomide forms an inclusion complex with HP-β-CD both in aqueous and in solid state. Phase solubility profile indicated that the solubility of leflunomide significantly increased in the presence of HP-β-CD and was classified as AL-type, indicating the 1:1 stoichiometric inclusion complexes in aqueous medium. The solid complexes prepared by different methods such as physical mixture, co-grinding method and freeze dried method in 1:1 and 1:2 molar ratio, were characterized by differential scanning calorimetry (DSC) and X-RD. The dissolution profiles of solid complexes were determined and compared with leflunomide alone and their physical mixture, different mediums such as simulated gastric fluid (pH 1.2) and simulated intestinal fluid (pH 7.4). The dissolution studies showed that, the freeze-dried complex exhibited higher dissolution rates than the drug, in the simulated gastric fluid (SGF pH 1.2) in 1:2 molar ratio.


Leflunomide, dissolution rate, cyclodextrin, phase solubility, inclusion complex.

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