Development And Evaluation Of The Drug Delivery System Of Gastrodia Chewing Gum

Objective: Gastrodia elata Bl.is a valuable traditional Chinese medicine that treats dizziness,hypertension,headaches and other symptoms;chewing gum is an oral chewing dosage form which is suitable for patients with dysphagia,and has characteristics of convenient taking,multiple absorption channels and immediate drug release.The subject aims to optimize the preparation process and evaluate Gastrodia chewing gums,meanwhile to develop a chewing preparations release apparatus for studying the release behavior of Gastrodia chewing gum.Methods: 1.Taking gastrodin,p-hydroxybenzyl alcohol,Gastrodia polysaccharide content and dry paste rate as evaluation indicators.The optimal extraction process of Gastrodia was selected by uniform design and effect surface method.Taking gastrodin,p-hydroxybenzyl alcohol,and Gastrodia polysaccharide content as evaluation indicators,the concentration process was determined by single factor method.The optimal prescription was selected by single factor method and D-optimal mixture design,with sensory evaluation,high temperature test,and low temperature test evaluated by nine-person,as well as moisture retention and ductility as inspection indicators.2.Quality evaluation: The chapter studied traits,identification,inspection,content determination and other items of Gastrodia chewing gum.The thin-layer chromatography(TLC)was used to identify gastrodin and p-hydroxybenzyl alcohol in Gastrodia chewing gum;the difference in moisture and weight was checked with reference to the "Chinese Pharmacopoeia"(2015 edition);differential scanning calorimetry(DSC)was used to measure the glass transition temperature,and the hardness of the product was measured by A-type Shore hardness tester.The content of gastrodin and p-hydroxybenzyl alcohol in Gastrodia chewing gums was measured by high performance liquid chromatography(HPLC).3.The release apparatus for chewing preparations was developed to fully simulate oral chewing behavior and evaluate the release behavior of Gastrodia chewing gum.Results: 1.The development of Gastrodia chewing gum:(1)the optimized extraction and concentration process is Rhizoma Gastrodiae slices adding 11 folds of water,soaking for 1h and decocting 3 times,2h each time.Mixed decoctions are concentrated under reduced pressure at 55°C to the extract with a relative density of 1.08-1.12.Development of Gastrodia chewing gum: mass percentage of gum base 16.84%,xylitol 43.93 %,glucose syrup-glycerol(2:1)16.84%,magnesium stearate 4.85%,menthol 0.84%,Gastrodia extract 16.70%.Put the prescription amount of gum base in a mortar and moisturize soften at 60°C for 30 minutes;add Gastrodia extract,glycerin,glucose syrup and 1/3 xylitol at 60°C and mix well;stir for15 min,then add 1/3 xylitol and mix for 5min,add 1/3 xylitol,menthol and magnesium stearate,stir for 5min;apply magnesium stearate to the pre-lubricated dough press,and press the gum block when cooled to 40℃,extrud into a cake and cut with mold,place at 22°C(RH50%)for16 hours to balance,then pack in aluminum foil and store in cool and dry place.2.Quality evaluation of Gastrodia chewing gum: The difference in moisture and weight meets the requirements of the Pharmacopoeia;the hardness and glass transition temperature are in line with the expectations,which can well reflect the palatability of the product;the TLC is specific to gastrodin and p-hydroxybenzyl alcohol in Gastrodia chewing gum;HPLC quantitative determination method of Gastrodia chewing gum has been established,for which the methodology investigation performs well.Gastrodia chewing gums contain gastrodin 1.40mg/g and p-hydroxybenzyl alcohol 0.22 mg/g.3.Evaluation of the release behavior of Gastrodia chewing gum: The release apparatus for chewing preparations has been successfully developed.The apparatus has a simple and stable transmission mode,which can be operated simply.It can evaluate six samples at the same time;the drug release behavior of Gastrodia chewing gum was investigated and strongly correlated with the chewing curve of volunteers.As a result,the active ingredient of Gastrodia chewing gum could be completely and stably released within 15 minutes.Conclusion: The development of Gastrodia chewing gum is reasonable and feasible,and the quality evaluation results perform well.The release apparatus for chewing preparations can be well-fitted with volunteers’ release curve by changing the parameters.The drug release curve of Gastrodia chewing gum provides a reference for evaluation of related chewing preparations.