Preparation Of Buoyant Extended Release Tablets Of Trimebutine Maleate For Gastric Retention

Trimebutine maleate is a new regulator of stomach and intestine function, which pKa is 6.25, so it is easy to resolve in acid than in basic solution. On the other hand, floating extended release tablets can be made to prolong its gastric retention time for its target is smooth muscle of stomach, meanwhile its bioavailability and compliance of patients can be both improved compared with common tablets that be taken 100mg or 200mg three times a day.Apparent equilibrium solubility, hygroscopicity, apparent coefficient of partition in oil/water and powder nature of trimebutine maleate was studied before formulation. Excipients was screened using initial floating time as effect by orthogonal experiment, then critical relative humidity was determined to offer reference of tabletting environment and storing condition as well as drug compatibility with excipients. It was indicated that the drug has high solubility in acid solution, a little hygroscopicity, poor flowability with its apparent coefficient of partition in oil/water increasing as pH value adding. Besides, there was no interaction between drug and excipients.Using central composite design combine overlaying contour map method and response surface method, In conclusion, overlaying contour map method was confirmed had least deviation.It is well-known that it is hard to evaluate gastric floating extended release tablets exactly for good floating property in vitro may not as so that in the stomach, leading to failure of the development. Obviously, it is not suitable to apply traditional release studying apparatus because of its especiality, that is, the tablets will adhere to the axle when floating, not only influenced physical strength produced by fluid but also the mechanical force. So based on other study, a new practical improved release determination apparatus was designed focus on that formulation. When fitting the release curve of the drug applying zero order kinetics, first order kinetics, unequal interval grey model and other models, it was found that Weibull distribution was the best one. When focus on floating mechanism, it was indicated it was main in axial direction as gastric floating extended release tablets swell. Besides, weight gaining ratio and swelling ratio determined floating properties. If the former was lowered and the later was increased, it was better for floating so that by cutting down tabletting pressure to improve floating properties was quite limited.Influential factor test showed this product was sensitive to humidity for weight gaining beyond 5% when exposed to high humidity environment(92.5%), at the same time, floating property was brought down. Considering this aspect, aluminium- plastics- aluminium package was taken. Accelerated test and long-term test indicated the product is stable during this period however longer stability test and preclinical study was under investigation.