Formulation Optimization of Gastro-Retention Tablets of Paeonol and Efficacy in Treatment of Experimental Gastric Ulcer.

This study aims to develop a gastroretentive sustained-release drug delivery system of paeonol using floating properties and to investigate its therapeutic effects in rat models. The gastric retention tablets of paeonol (GRT-Ps) were prepared by a direct compression method, and the Box-Behnken design was used to optimize its formulation. The optimized formulation containing 15% NaHCO3 and a 2 : 1 ratio of paeonol and HPMC-K4M floated within 1 min and remained afloat for more than 8 h in the simulated gastric fluid (200 mL, pH=1.2) and simultaneously showed the desired sustained drug release. Moreover, small tablets (3 mm) were prepared according to the same formulation and the process technology of big tablets (8 mm). A similar drug release behavior was observed between two kinds of tablets (f2=52), and then the evaluations of efficacy and retention capacity in vivo were conducted with small tablets. In vivo retention studies showed that the Tmax (2 h) of GRT-P in rat stomachs was significantly extended compared with the Tmax (0.5 h) of normal reference preparation. Compared with the model group, low and high doses of GRT-P could significantly inhibit the increase of malondialdehyde (MDA) in serum. Studies showed that the higher MDA content in inflammation tissue increases the inflammatory response. The ulcer inhibition rates of GRT-P in the high-dose group were 59.0 and 64.1% in the ranitidine group. Results indicated that GRT-Ps had the potential for a sustained drug release and an enhanced gastric residence time with relatively high drug concentrations in the tissue distribution.