Abstract

Nitazoxanide (NTZ) is a synthetic form of nitrothiazole with a broad range of applications as an antiparasitic, antibacterial and antiviral agent. NTZ is a highly low aqueous soluble drug which possesses solubility of 0.00755 mg/mL and typically low bioavailability of 1%. Low aqueous solubility is usually regarded as prime prerequisites for enhanced absorption and bioavailability. The purpose of this study is to improve in vitro dissolution of the poorly soluble drug NTZ through amorphous solid dispersion technology. Three solid dispersions of NTZ were successfully prepared by hot-melt technique. It was further evaluated for drug content, DSC, XRD, SEM, TEM, FT-IR, in-vitro drug release study, in vitro MTT safety on HEK-293 and A-549 and stability study. The results of XRD showed after the formation of solid dispersions. The number of crystalline peaks has disappeared and confirmed the amorphous form of the drug. An in vitro release study showed that NTZ effectively released from solid dispersion into a simulated gastric releasing medium (pH 1.2). Further, the cytotoxicity study gave an indication of safe for human. Also, stability studies depicted no evident difference in the physical state of solid dispersion after six months. Hence, it can be concluded that the newly developed formulation was found to be safe and stable with enhanced solubility profile.

摘要

硝唑尼特（NTZ）是硝噻唑的合成形式，具有广泛的用途，可作为抗寄生虫剂，抗菌剂和抗病毒剂。NTZ是一种高度低水溶性的药物，其溶解度为0.00755 mg / mL，通常生物利用度低至1％。低水溶性通常被认为是增强吸收和生物利用度的主要前提。本研究的目的是通过无定形固体分散技术改善难溶性药物NTZ的体外溶出度。通过热熔技术成功地制备了三种NTZ固体分散体。进一步评估了药物含量，DSC，XRD，SEM，TEM，FT-IR，体外药物释放研究，体外MTT对HEK-293和A-549的安全性和稳定性研究。固体分散体形成后的XRD结果表明。结晶峰的数量已经消失，并确认了药物的无定形形式。的体外释放研究表明，NTZ有效地从固体分散体释放到模拟胃液释放介质（pH为1.2）。此外，细胞毒性研究表明对人类安全。同样，稳定性研究表明六个月后固体分散体的物理状态没有明显差异。因此，可以得出结论，发现新开发的制剂是安全和稳定的，具有增强的溶解度曲线。