Physico-Chemical Characterization and In Vitro Dissolution Assessment of Clonazepam—Cyclodextrins Inclusion Compounds |
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Authors: | Rakesh Patel Nirav Purohit |
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Institution: | (1) Department of Pharmaceutics and Pharmaceutical Technology, S. K. Patel College of Pharmaceutical Education and Research, Ganpat University, Kherva, Mehsana-Gozaria Highway, PIN-382711 Mehsana, Gujarat, India |
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Abstract: | The objectives of this research were to prepare and characterize inclusion complexes of clonazepam with β-cyclodextrin and
hydroxypropyl-β-cyclodextrin and to study the effect of complexation on the dissolution rate of clonazepam, a water-insoluble
lipid-lowering drug. The phase-solubility profiles with both cyclodextrins were classified as AP-type, indicating the formation of 2:1 stoichiometric inclusion complexes. Gibbs free energy ( DGtro ) \left( {\Delta {G_{tr}}^o} \right) values were all negative, indicating the spontaneous nature of clonazepam solubilization, and they decreased with increase
in the cyclodextrins concentration, demonstrating that the reaction conditions became more favorable as the concentration
of cyclodextrins increased. Complexes of clonazepam were prepared with cyclodextrins by various methods such as kneading,
coevaporation, and physical mixing. The complexes were characterized by Fourier transform infrared spectroscopy and differential
scanning calorimetry studies. These studies indicated that complex prepared kneading and coevaporation methods showed successful
inclusion of the clonazepam molecule into the cyclodextrins cavity. The complexation resulted in a marked improvement in the
solubility and wettability of clonazepam. Among all the samples, complex prepared with hydroxypropyl-β-cyclodextrin by kneading
method showed highest improvement in in vitro dissolution rate of clonazepam. Mean dissolution time of clonazepam decreased significantly after preparation of complexes
and physical mixture of clonazepam with cyclodextrins. Similarity factor indicated significant difference between the release
profiles of clonazepam from complexes and physical mixture and from plain clonazepam. Tablets containing complexes prepared
with cyclodextrins showed significant improvement in the release profile of clonazepam as compared to tablet containing clonazepam
without cyclodextrins. |
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