Badshah Syed Faisal, Abdullah Orva, Khan Kifayat Ullah, Hussain Abid, Mukhtiar Muhammad, Barkat Kashif, Jan Nasrullah, Khan Samiullah, Aamir Muhammad, Liaqat Huma, Mehmood Yasir, Jabbar Abdul, Waqar Maham, Khanum Tehreem
Department of Pharmacy, Faculty of Medical and Health Sciences, University of Poonch Rawalakot, Azad Jammu and Kashmir, Pakistan.
Hamdard Institute of Pharmaceutical Science, Hamdard University, Islamabad, Pakistan.
Biomed Mater. 2024 Dec 12;20(1). doi: 10.1088/1748-605X/ad9803.
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,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.
本研究的目的是提高氯噻酮的溶解度。氯噻酮是一种难溶性利尿剂，在过去半个世纪一直用于降低高血压。对于大约90%的候选药物来说，溶解度是一个挑战。氯噻酮属于BCS IV类药物，其溶解度差，需要改善以优化其疗效。采用自由基聚合技术，制备了基于海藻酸钠的纳米凝胶以提高氯噻酮的溶解度。通过结构表征、载药量、溶胀、溶胶-凝胶转变、释放、溶解度和毒性测试对纳米凝胶的各种特性进行了评估。傅里叶变换红外（FT-IR）光谱显示了主要原料和聚合物纳米凝胶的特征峰。载有氯噻酮的纳米凝胶的FT-IR光谱显示出离散的药物峰，证实药物成功载入。粉末X射线衍射和热分析表明了该体系的无定形性质和热稳定性。扫描电子显微镜显示出明确的多孔结构。通过zeta尺寸分析确定纳米凝胶的尺寸为189±18.35纳米。溶解度增强因子表明了改善难溶性药物溶解度的潜力。所得的生物相容性纳米凝胶可用于提高疏水性药物的溶解度。
