Thiazolidinedione as an alternative to facilitate oral administration in geriatric patients with Alzheimer's disease

Abstract

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.

Keywords: Alzheimer's disease; Geriatric patients; Mucosal permeation; Oral administration; Pioglitazone; Thiazolidinediones.