Sodium alginate based fast swelling nanogels for solubility enhancement of chlorthalidone; synthesis, characterization and biosafety evaluation

Purpose of the study was to enhance the solubility of chlorthalidone, poorly soluble diuretic that has been the used for lowering high blood pressure for the past half-century. Solubility is a challenge for approximately 90% of drug candidates. Chlorthalidone is BCS Class IV drug whose poor solubility needs to be improved in order to optimize its efficacy. Using a free radical polymerization technique, sodium alginate-based nanogels were formulated for enhancing solubility of chlorthalidone. The evaluation of various characteristics of nanogels was done by structural characterization, drug loading, swelling, sol-gel transition,<i>in-vitro</i>release, solubility, and toxicity tests. Fourier transform infrared (FT-IR) spectroscopy revealed characteristic peaks of the primary raw materials and polymeric nanogels. The FT-IR spectra of the chlorthalidone-loaded nanogels suggested discrete drug peaks confirming successful drug loading. The system's amorphous nature and thermal stability were indicated by powder x-ray diffractometry and thermal analysis. The scanning electron microscopy indicated a well-defined porous structure. The size of the nanogels was determined by zeta size analysis to be 189 ± 18.35 n·m. The solubility enhancement factor demonstrated the potential for improved solubility of the poorly soluble drug. The resulting biocompatible nanogels could be used to improve the solubility of hydrophobic drugs.