Experimental measurement - correlation of solubility and dissolution thermodynamics study of itraconazole in pure monosolvents at various temperatures.

The information about the solubility and thermodynamic properties of solution is important for pharmaceutically important processes, formulation development, and further theoretical studies. In the present study, the solid-liquid equilibrium (solubility) for itraconazole (ITC) was determined experimentally in 14 monosolvents at temperatures between 293.15 K and 318.15 K under pressure of 0.1 MPa. The mole fraction solubilities were found to increase with increasing temperatures and followed inverse trend with the polarity of selected solvents. Besides, KAT-LSER analysis was performed to study the effect of solvent. The results revealed that the solute-solvent interaction (43.94%) was much higher than that of solvent-solvent interaction (16.59%). Thermodynamic based models like van't Hoff equation, modified Apelblat equation, Buchowski-Ksiazaczak equation, and polynomial empirical equation were applied to fit and correlate the experimental solubilities. Overall relative average deviation (RAD) and overall root-mean square deviation (104×RMSD) were observed to be minimum with the empirical polynomial equation and attained the values of 0.0033 and 0.0047, respectively. Furthermore, theoretical ideal solubilities, activity coefficients, and thermodynamic properties of dissolution including molar enthalpy, molar entropy, molar Gibbs free energy, and excess enthalpy were estimated. Ideal solubilities were projected considerably higher than experimental solubilities at each studied temperature. Thermodynamic properties of dissolution indicated that the dissolution was not a spontaneous process; observed to be endothermic (ΔH0soln>0) and enthalpy driven (ΔS0soln>0). Such solid-liquid equilibrium data of ITC will be of immense help in process and formulation development in pharmaceutical sciences.

Solubilization and determination of solution thermodynamic properties of itraconazole in different solvents at different temperatures.

The solubility of itraconazole (ITRA) in thirteen pure solvents including water, dimethyl sulphoxide, acetonitrile, methanol, 1,4-butanediol, ethanol, isopropyl alcohol, n-butanol, octanol, ethyl acetate, toluene, benzene, 1,4-dioxane were estimated at the temperatures ranging from 293.15 K to 318.15 K under atmospheric pressure (0.1 MPa). The results reflected that the solubility of ITRA was a function of temperature and was increased with a rise in temperature in each solvent. Moreover, the solubility in polar solvents was less and found to be increased in non-polar solvents. Furthermore, the results of solubilization were correlated by the Van't Hoff equation, the modified Apelblat equation, the Buchowski - Ksiazaczak λh equation, and the polynomial empirical equation. The polynomial empirical equation proved to be more accurate and suitable for the correlation of solubilities of ITRA in studied solvents at various temperatures. Besides, theoretical ideal solubilities, activity coefficients, and thermodynamic properties of the solution process including standard molar enthalpy, entropy, Gibbs free energy, and excess enthalpy were calculated from the experimental solubility data. These thermodynamic parameters indicated that the solubilization process was not spontaneous, endothermic, and enthalpy driven. Such thermodynamic based solubility data of ITRA will be of immense help in solubilization, synthesis, process development, preformualtion, and dosage form development in pharmaceuticals.

Enhancement of Dissolution of Fenofibrate Using Complexation with Hydroxy Propyl ß-Cyclodextrin.

OBJECTIVES: The aim of the present study was to enhance the dissolution rate of fenofibrate using complexation with hydroxy propyl ß-cyclodextrin (HPßCD). MATERIALS AND METHODS: The phase solubility behavior of fenofibrate was studied in various concentrations of (HPßCD) aq. solution at 37°C. The solubility of fenofibrate increased with an increase in the amount of HPßCD aq. solution. Gibbs free energy (ΔG°)tr values were all negative. Complexes of fenofibrate with HPßCD were prepared in 1:1 ratio by kneading and coprecipitation. These complexes were evaluated by dissolution studies, fourier transform infrared (FTIR) spectroscopy, and differential scanning calorimetry (DSC) studies. RESULTS: The complexation of fenofibrate with HPßCD exhibited an enhanced dissolution rate. The mean dissolution time of fenofibrate decreased significantly upon complexation. FTIR studies showed the formation of intermolecular hydrogen bonding between fenofibrate and HPßCD. DSC studies indicated a loss in crystalline state of fenofibrate in complexes. CONCLUSION: Complexation with HPßCD can be used as a useful tool for the enhancement of dissolution of fenofibrate.