| "Ganershu prescription" was consisted of Sedum Sarmentosum,Bupleurum and the forth.Based on the extraction,separation,we further combined with preformulation study results of intermediate powder.Then the sustained-released Ganershu mini-pill was designed,prepared and used to test a preliminary stability study.The objective of present study was to establish a method for Chinese herbal extracts that has the properties of high viscous and hygroscopicity to prepare sustained-released mini-pill.The main research contents are as follows:1.The preformulation researchDetermination methods of the total flavonoids and total saponins in the bioactive fraction of Ganershu prescription were established.Even more,the galuteolin in Sedum Sarmentosum was also detected by HPLC method.The preformulation study showed that in different mediums the intermediate powders both had the good solubility;the extracts were with a poor fluidity,which indicated by the angle of repose was greater than 40°;the critical relative humidity of 50%showed a strong hygroscopicity;the bulk density of 0.619g·cm-3 and the porosity of 14.51%both resulted from a minor porosity.Stability study showed that the powders had the good photostability and thermostability,but the moisture absorption was strong which result in the serious adhesion.The parameters of physical and chemical property in preformulation research provided a reference for preparation process in further study.2.Dosage form design and preparationIn the process of the dosage form design,the feasibility of forming skeleton-type tablets,skeleton-type pellets and film control pellets were investigated.The results indicated that film control pellets was more reasonable for sustained-release preparation.The parameters of blank pill core forming process were optimized by orthogonal design.The blank pill core were obtained by the starch,dextrin,1%CMC-Na solution,and process paramenters were optimized through orthogonal design.The parameters of drug-loaded pellets forming process were optimized by central composite design.The Ganershu intermediate powder was made for 30%ethanol solution 1.14 g·mL-1.And then 6%talc was added as anti-adhesive agents.Subsequently,the alcohol solution was sprayed in fluidizing chamber under 300 kPa atomization pressure,pump speed for 4 r·min-1,dial height 5 mm,inlet air temperature 75 ?,the blower frequency of 25?40 Hz and turntable speed 300 r·min-1 to obtain the ordinary pellets.In addition,the release rates of total flavonoids,total saponin and luteolin were selected as indicators to investigate the optimal parameters of sustained release coating by the fluidized bed bottom-spraying process.The technical process parameters:pump speed 4 r·min-1,atomization pressure of 250 kPa,inlet air temperature 45 ? and blower frequency 30 Hz.Subsequently,the swelling agent(inner layer of clothing)was packaged with 4.5%(g·mL-1)HPMC.After the weight gained of 6%,the extended-release layer(outer layer of clothing)was coated with surelease aqueous dispersion.Thus,the weight gained of 22%,and then the Ganershu sustained-release pellets were obtained.3.The preliminary stability studyThe results of preliminary stability investigation of Ganershu sustained-release pellets showed that the preparation is more stable for light and temperature.There were no significant changes in the content and release.However,in high humidity condition of RH92.5%,the moisture situation is more serious.But in the humidity conditions of RH75%,the appearance,content and release had no significant change.Even so the preparations should pay more attention to dampproof. |
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