(T1030-03-18) Solubility Measurement and Modeling of Bisacodyl in Mono Solvent and Binary Solvent Mixture, and Its Application for Pharmaceutical Industry

Purpose: The purpose of study was to measure the solubility of bisacodyl in various solvents at different temperatures, and to identify correlations of experimental data with calculation data by applying several computational models. Furthermore, it could be applied to pharmaceutical industry, using these data.

Methods: The solubility in various solvents was determined using the solid-liquid equilibrium method under atmospheric pressure condition. The concentration of bisacodyl in solvents was analyzed using a HPLC system. To confirm degradation and/or crystalline transformation of samples, it was utilized by DSC and PXRD analyses. The KAT-LSER was applied to identify the effect of solvent-solute interactions on the solubility. The experimental solubility data for bisacodyl was fitted by computational models. Nanosuspensions containing bisacodyl were prepared by using previously reported antisolvent precipitation system.

Results: The solubility study for bisacodyl was performed in various solvents from 288.15 to 308.15 K. The solubility was slightly increased with increasing temperature in all solvents. In this study, the solubility in N-methyl-2-pyrrolidone (NMP) is 420,896 folds in comparison to water at 298.15K. It is considered that NMP, dimethylacetamide (DMA), and dimethylformamide (DMF) have a solvent ability for bisacodyl because of its high dielectric constant and one-sided dipole moment. The solubility in binary solvent mixtures was additionally performed at same temperature range. It was confirmed that the solubility improves with increasing temperatures and mass fraction of NMP in the binary solvent mixtures, and the solubility of bisacodyl reached the maximum in pure NMP (w=1). Furthermore, it was confirmed that the crystal form of recovered bisacodyl after equilibrium state in solvent was not changed through the analysis of PRXD pattern. Based on these solubility data, the nanosuspension prepared under certain conditions had an average particle size of less than 100 nm.

Conclusion: The solubility of bisacodyl in NMP was the highest and in water was the lowest. Based on experimental data conducted in study, the nanosuspensions of bisacodyl was prepared using liquid antisolvent precipitation. As a result, nanosuspensions could be prepared by changing the drug concentration and the ratio of NMP in the binary solvent mixtures. Furthermore, it can be utilized for pharmaceutical industry through solubility data and established equations. Therefore, it can be concluded that the antisolvent precipitation system based on the drug solubility data is a prospective method for manufacture of nanosuspensions.

Mole fraction solubility (x) of bisacodyl in mono solvents.

Mole fraction solubility (x) of bisacodyl in NMP + water mixed solvents.