Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain; Institute of Nanoscience and Nanotechnology (IN2UB), University of Barcelona, 08028 Barcelona, Spain.
Department of Pharmacy, Pharmaceutical Technology and Physical Chemistry, Faculty of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain; Departamento de Química y Ciencias Exactas, Universidad Técnica Particular de Loja, Loja 1101608, Ecuador.
Eur J Pharm Sci. 2019 Mar 1;129:173-180. doi: 10.1016/j.ejps.2019.01.008. Epub 2019 Jan 9.
Pioglitazone (PGZ) is a member of the thiazolidinedione (TZDs) family of drugs and it is primarily used to treat type 2 diabetes. Previous studies have reported anti-inflammatory and neuroprotective effects in the central nervous system. Building on this, the aim of this study was to develop an oral solution of PGZ (PGZ-SOL) as an alternative treatment for geriatric patients with Alzheimer's disease (AD). Solubility of PGZ was evaluated to establish the solution composition. Parameters determined were pH, rheology, extensibility and retention time. In vitro diffusion kinetic profile and ex vivo permeation studies were carried out in Franz diffusion cells using buccal, sublingual, nasal and intestinal mucosae. The toxicity of PGZ-SOL was evaluated by in vivo model using BALB/c mice. PGZ-SOL exhibited a Newtonian behavior as well as physical and chemical stability during a period of three months. The diffusion profile of PGZ from formulation followed a first-order kinetic model. The biopharmaceutical parameters revealed high permeability of PGZ via intestinal mucosa. Finally, oral administration of PGZ-SOL did not cause damage of buccal, sublingual and intestinal mucosae which suggests that this formulation is a viable alternative for AD treatment in geriatric populations with difficulty swallowing conventional solid dosage forms.
吡格列酮（PGZ）是噻唑烷二酮（TZDs）类药物的成员，主要用于治疗 2 型糖尿病。先前的研究报告称其在中枢神经系统具有抗炎和神经保护作用。在此基础上，本研究旨在开发 PGZ 的口服溶液（PGZ-SOL），作为治疗老年阿尔茨海默病（AD）患者的替代疗法。评估了 PGZ 的溶解度以确定溶液的组成。确定的参数包括 pH 值、流变学、延伸性和保留时间。在 Franz 扩散细胞中使用颊黏膜、舌下黏膜、鼻腔黏膜和肠黏膜进行体外扩散动力学研究和体外渗透研究。通过 BALB/c 小鼠的体内模型评估 PGZ-SOL 的毒性。PGZ-SOL 表现出牛顿行为以及在三个月的时间内具有物理和化学稳定性。制剂中 PGZ 的扩散曲线遵循一级动力学模型。生物制药参数显示 PGZ 通过肠黏膜具有高渗透性。最后，PGZ-SOL 的口服给药不会引起颊黏膜、舌下黏膜和肠黏膜的损伤，这表明该制剂是吞咽常规固体制剂有困难的老年人群 AD 治疗的可行替代方案。
