Studies On Controlled Porosity Osmotic Pump Tablets Of Extract Of Lysimachia Clethroide Duby

In this paper, the extract of Lysimachia clethroide Duby, which has the efficacy of anti-tumor, was used as the model drug to prepare the tablets. According to the physicochemical property of the extract, we designed a safe, efficient, steady and reasonable dosage form-osmotic pump tablets.Two components of the extract of Lysimachia clethroide Duby, rutin and Naringenin-7-O- Glucoside were used to evaluate the release behavior of self-made osmotic pump tablets. A HPLC gradient elution method for simultaneous determination of rutin and Naringenin-7-O-Glucoside in Lysimachia clethroide Duby was established, and a better separating effect was obtained in this paper. This method is accurate,simple and can provide some reference for the further study of flavonoids in Lysimachia clethroide Duby.Cellulose acetate free films were prepared by the plate welding method, and properties such as the moisture permeability of CA free film, Intrinsic viscosity of coating dissolvent and weightlessness after the film exposed to water were studied detailed. The influence of the concentration of coating dissolvent, the content of plasticizer and the content of pore forming agent on the properties of free films were investigate, respectively. The results of study on moisture permeability of free films indicated that the moisture permeability grew when the content of PEG400 increased. The results of study on weightlessness showed that the more content of PEG400 added to the coating dissolvent, the more weightlessness of free films after it exposed to water. The results of determination of viscosity of coating dissolvent showed that the addition of plasticizer can improve the intrinsic viscosity of coating dissolvent.Under the firmed coating parameters conditions, we studied the factors that influencing the release behavior of controlled-release tablets, such as the kind of diluent agent, the amount of osmotic promoting agent, hardness of tablet, membrane compositions, etc. Furthermore, we studied the influence of coating parameters and the conditions of drug release on the release behavior of the osmotic pump tablets. Similar factor method was used to analyze factors influencing drug release behavior, and the optimal formulation was selected by the orthogonal design. The optimal formulation of the osmotic pump tablets were as follows: ZTF 20.0g, NaCl 15.0g, starch 5.5g, lactose 5.5g, NaHCO₃ 4.0g, SiO₂ 4.0g and magnesium stearate 2.0g. The optimal formulation of membrane were as follows: CA 4.0g, PEG400 4.0g, DBP 0.8g, acetone 200mL and weight increment of membrane 4%. The optimal coating parameters were as follows: temperature of coating 40℃, speeds of coating pan 35r/min, spray rate 2.5mL/min and spray pressure 1kg/m². According to the optimal formulation, three batches of osmotic pump tablets were made and good similarity was exhibited. The stability of the self-made osmotic pump tablets was investigated under condition of room temperature, 60℃, RH75%, RH92.5%, light intensity of 4800Lx, etc. The release profile of The controlled porosity osmotic pump tablets of extract of Lysimachia clethroide Duby exhibited a zero-order process within 12h.The pharmacokinetic study of the self-made controlled release tablets were performed in four healthy dogs through two-period and crossover design, drug concentration in plasma of dogs administered with single dose was detected by HPLC method. The pharmacokinetic parameters of rutin in the test and reference tablets were as follows: T_max were 7.7554±1.92 and 5.900±0.69 h, C_max were 0.1939±0.0353 and 0.3443±0.1680μg/mL, AUC₍0-t were 1.8082±0.7064 and 1.5780±0.2644μg·h/mL. The time-concentration curves of the test and reference tablets were plotted. And the results indicated that the self-prepared osmotic pump tablets can provide a more persistent plasma level than the reference tablets. The relative bioavailability of the test tablets compared with the reference tablets was 116.09%. The correlation-ship of drug release behavior was studied according to W-N equation and the results indicated that there was a good correlation-ship between vitro and vivo(r =0.9631).