Study On Theophylline Curdlan Oral Sustained-release Gel

Curdlan is an extracellular bacterial polysaccharide,β-1,3-D-glucan, produced by Alcaligenes faecalis var.. It is tasteless, esculent and has no evident toxicity. Curdlan has been used as a food additive which is added to various food in Japan and USA. But it has not yet been used in practical pharmaceutical dosage forms. In the study, we prepared theophylline Curdlan oral sustained-release gel by heating an aqueous suspension of Curdlan. Theophylline was used as a model drug and Carbopol as sustained-release material.The essential physicochemical properties were tested, such as the distribution of particle, the flowability and the solubility, etc. At the same time, the mechanism of gelation was analyzed by DSC and rheological analyses.The methods in vitro of drug release from theophylline Curdlan oral sustained-release gel were established. The various factors which affected the release of theophylline from theophylline Curdlan oral sustained-release gel were investigated preliminary, such as the concentration of Curdlan, the heating temperature, the sorts of and the concentrations of additives, etc. The formulations were op(?)timized using SAS software. A new dosage—theophylline Curdlan oral sustained-release gel were successfully prepared.The study showed that the drug release characteristics, appearance and the content of theophylline in the gel did not change under 40℃and RH75% for three months. Based on the studies of the influence of formulation and manufacture on the release of theophylline,the sustained-release gel were prepared with Curdlan and Carbopol. The formulation were optimized by central composite design, with accumulative release amount of 1 h 2 h 4 h and 8 h as the evaluation target. The release of theophylline could be described as First order, Higuchi and Ritger-Peppas equation.The concentrations of theophylline in plasma were determined by HPLC method. Theophylline sustained-release tablets was used as the reference formulation. Pharmacokinetics of theophylline Curdlan oral sustained-release gel were performed in 6 healthy rats. The relative bioavailability of theophylline Curdlan oral sustained-release gel were 90.1%. Obvious relation was observed between absorption percentage in vivo and release rate in vitro.