SOLUBILITY OF ILAPRAZOLE IN VARIOUS ALCOHOLS IN TEMPERATURE RANGE BETWEEN (298.15 TO 322.15) K

. The solubility of Ilaprazole in methanol, ethanol, 2-propanol and n-butanol was measured using a gravimetrical method at temperature ranging from 298.15 K to 322.15 K. The results of these measurements were correlated with a semi empirical equation. Some thermodynamic parameters such as dissolution enthalpy, Gibb’s free energy, and entropy of mixing have also been calculated.


INTRODUCTION
The production of pharmaceuticals involves solvent selection as a function of solubility, for formulation, purification and chemical reaction. Selection of optimum solvent for a particular application is important for developing efficient process. Further, solubility data is required for cost effective manufacturing processes.
Ilaprazole is a newly developed proton pump inhibitor 1 for the treatment of dyspepsia, peptic ulcer disease, gastroesophageal reflux disease 2 and duodenal ulcer. 3,4 Literature survey shows that most of work reported for Ilaprazole is focused on the pharmacology, pharmacokinetics, metabolism, and quantitative determination. [5][6][7][8][9][10] Due to these medicinal importance, it would be interesting to study the solubility of this drug in some solvents. The solubility data of this drug may be useful for its applications in other fields also.
Thus, in the present work, solubility of Ilaprazole is studied by a gravimetric method in some alcohols; methanol, ethanol, 2-propanol, and n-butanol over a temperature range (298.15 K to 322.15 K) at atmospheric pressure.

RESULTS AND DISCUSSION:
The mole fraction solubilities x of Ilaprazole in methanol, ethanol, 2-propanol and n-butanol at different temperatures (298.15 to 322.15 K) are presented in Table 1 and more visually given in Figure 2. It is observed that the solubility is minimum in n-butanol and maximum in methanol. Further, solubility increases nonlinearly with temperature.
The temperature dependence of Ilaprazole solubility in pure solvents was described by the modified empirical equation 11,12 : (1) where T is the absolute temperature, and A, B, and C are empirical constants. The values of these parameters are listed in Table 2.
The root-mean-square deviations (RMSD) are calculated using the following equation: (2) where N is the number of experimental points and x and x i represent the mole fraction solubility of the experiment and that calculated from eq 1, respectively. These values are given in Table 2. Further, relative deviations (RD) and relative average deviations (ARD) are calculated by eq (4) and (5) and are listed in Tables 1 and 2 respectively. (3) (4) where N is the number of experimental points and x i is the solubility calculated by eq 1.
The dissolution of a substance in a solvent is associated with changes in thermodynamic parameters such as enthalpies of solution (H sol ), Gibb's energy of dissolution (ΔG sol ) and entropy of solutions (S sol ). The changes that occur in the solute during dissolution process can be explained by these thermodynamic functions. These parameters have also been evaluated from experimental solubility data.
The enthalpies of solution (H sol ) was calculated by modified van't Hoff equation 13,14 i.e., from the slope of the plot of lnx versus (1/T -1/T hm ).
where T is the experimental temperature and R is gas constant. T hm is the mean harmonic temperature which is given as (6) where n is the number of experimental temperatures 15  From the intercepts of these plots, Gibbs energy change (ΔG sol ) for the solubility process were evaluated by the following relation 13 : Using these evaluated H sol and G sol values, the entropies of solutions S sol were obtained from equation 13,14 All these thermodynamic parameters are given in Table 3. It is evident from Tables 3 that   for the

Solubility measurement:
The gravimetric method was used to study the solubility. An excess mass of drug was added to a known mass of solvent. The solution was heated to a constant temperature with continuous stirring. The stirring was stopped after few hrs and the solution was allowed to approach equilibrium. This solution was then filtered and by a preheated injector, 2 ml of this clear solution was taken in another weighted measuring vial (m 0 ). The vial was quickly and tightly closed and weighted (m 1 ) to determine the mass of sample (m 1 -m 0 ). Then the vial was covered with a piece of filter paper to prevent dust contamination. After the solvent in the vial had

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ILCPA Volume 51 completely evaporated at room temperature, the vial was dried and reweighted (m 2 ) to determine the mass of the constant residue solid (m 2 -m 0 ). All of the masses were taken using an electronic balance (Mettler Toledo AB204-S, Switzerland) with an uncertainty of ± 0.0001 g. Thus, the mole fraction of the solid sample in the solution, x, can be determined by the following relation: (9) where M 1 is the molar mass of Ilaprazole and M 2 is the molar mass of solvent. At each temperature, the measurement was repeated three times and average value is given in Table 1.

Acknowledgement
Authors are thankful to Head of Chemistry department for providing necessary facilities.    Figure 1: Chemical structure of Ilaprazole.