| dc.description.abstract | More than 65% of new drug candidates in pharmaceutical industry are poorly aqueous soluble drug. Co-crystallization technique can be used to overcome this problem through enhancing the high-end product purification and bioavailability of the drug by combining the API (Active Pharmaceutical Ingredient) with the co-former agent. In this work, co-crystallization of benzoic acid as the API with sodium benzoate as the co-former in co-solvent of 4:1 v/v of ethanol-water was generated by reaction crystallization method. A clear saturated solution was prepared by diluting Solution A containing 17.22 g (0.141 mol) of benzoic acid (HBz) in 50 mL of 4:1 v/v ethanol – water co-solvent and Solution B containing 1.89 g (0.047 mol) of sodium hydroxide (NaOH) in 6 mL of 2:1 v/v ethanol – water co-solvent. The solution then was cooled from room temperature to 16oC until the crystals were generated and the solution became turbid, indicating that the system had reached the end of the induction time, τ, of crystallization which can be used to determine some fundamental kinetic and thermodynamic parameters of nucleation and crystal growth, such as: the interfacial energy, γ, the Gibbs energetic barrier, ΔGcr, the nucleation rate, J, the critical size of stable nuclei, rc, and the relative growth rate, RG. All of these parameters were evaluated with different initial supersaturation ratio of the system, S0, which were: 1.66, 1.54, 1.48, and 1.43. To study the effect of templating in co-crystal system, about 1.5 wt % template of: sodium benzoate, 2:1 co-crystal of benzoic acid-sodium benzoate, and 1:1 co-crystal of benzoic acid-sodium benzoate were
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introduced for each system with different S0. In general, the induction times for all systems ranged from 3 to 40 minutes, where the higher S0 value gave the faster τ value. Moreover, introducing a template in the system gave a faster induction time, τ. ΔGcr and rc decreased, while J and RG increased on a faster induction time, indicating that co-crystallization thermodynamic and kinetic were directly related to the initial concentration of the drug. The final product of the solid crystals for each system was verified as 2:1 co-crystal of benzoic acid – sodium benzoate by PXRD, FTIR, DSC, and TGA. Finally, these results showed that co-crystallization of API, benzoic acid, with its co-former, sodium benzoate, was feasible, both kinetically and thermodynamically. | en_US |