Effect of Cyclodextrin Complexation on the Aqueous Solubility of Diazepam and Nitrazepam Phase-Solubility Analysis, Thermodynamic Properties.docVIP

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Effect of Cyclodextrin Complexation on the Aqueous Solubility of Diazepam and Nitrazepam Phase-Solubility Analysis, Thermodynamic Properties.doc

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Effect of Cyclodextrin Complexation on the Aqueous Solubility of Diazepam and Nitrazepam Phase-Solubility Analysis, Thermodynamic Properties

American Journal of Analytical Chemistry, 2012, 3, 811-819 /10.4236/ajac.2012.312107 Published Online December 2012 (http://www.SciRP.org/journal/ajac) Effect of Cyclodextrin Complexation on the Aqueous Solubility of Diazepam and Nitrazepam: Phase-Solubility Analysis, Thermodynamic Properties Jasmina Had?iabdi?, Alisa Elezovi?, Ognjenka Rahi?, Indira Mujezin Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Sarajevo, Sarajevo, Bosnia and Herzegovina Email: hadziabdicjasmina@ Received October 12, 2012; revised November 22, 2012; accepted November 30, 2012 ABSTRACT The solubility enhancement of diazepam and nitrazepam in water was analyzed depending on temperature and amount of α-cyclodextrin (α-CD), β-cyclodextrin (β-CD) and 2-hydroxypropyl-β-cyclodextrin (2-HP-β-CD). The interactions of drug-cyclodextrin in solution were investigated by the phase-solubility analysis. Diazepam (nitrazepam) content in aqueous complexation medium was analyzed UV spectrophotometrically. Classical solubility data were used to derive apparent stability constants (K ) which were used to derive thermodynamic parameters for the diazepam (nitraze- 1:1 pam)-cyclodextrin complexes. Since all phase solubility plots were of A types, and calculated Slopes after linear re- L– gression analysis were found to be less than 1, it could be assumed that stoichiometry of the formed binary systems was 1:1. According to the calculated K1:1 values, the stability of the complexes of diazepam and nitrazepam with α-CD, β-CD and 2-HP-β-CD varies as follows: 2-HP-β-CD β-CD α-CD. Theα-CD has higher affinity for dissolving ni- trazepam compared to diazepam. While all parameters lead to an improvement in solubility, the largest effect was obtained for guest-host complexation with 2-HP-β-CD. The solubility of diazepam and nitrazepam in water increased 93.02 times and 64.23 times, respectively, in the presence of 40% (w/w)