Preparation And Application Of PH-Position-Release Hollow Capsules With Red Algae Polysaccharide

The plant-derived pH-position-release hollow capsules were prepared withκ,ι,andλthree red algae polysaccharides.The study was divided into three parts,the contents were as follows:PartⅠ:The rheological properties and film-forming properties with three types of red algae polysaccharides（κ,ιandλ）were studied systematically.The results were as follows:（1）Effect of concentration on viscosity of red algae polysaccharides:The experimental results showed that the concentration had a strong influence on the viscosity of the three types of red algae polysaccharides,and both raised with the increase of the concentration.Among them,κ-type red algae polysaccharide had the strongest change in gel strength.Theλ-type red algae polysaccharide did not coagulate at room temperature.At the same concentration,the viscosity of theι-type red algae polysaccharide was the lowest,so it becomed the best material for preparing the hollow capsule by dipping glue method.（2）Effect of pH on viscosity of the glue:The experimental results showed that the viscosity of the three types of red algae polysaccharides ofκ,ι,λhad low viscosity and viscous instability under acidic conditions,and the viscosity tended to be stable in neutral and alkaline conditions.The viscosity increased first and then decreased with the increase of pH.When the red algae polysaccharide sol was used,the water pH was preferably 6-8.（3）Sensitivity of ion to red algae polysaccharide gum viscosity and gel strength:Test results showed that:By mixing 0.5%ion concentration of Na⁺,K⁺and Ca²⁺with 1%of three types of polysaccharides found that:K⁺was sensitive to the viscosity and gel strength of theκ-type red algae polysaccharide,Ca²⁺was sensitive to the viscosity and gel strength of theι-type red algae polysaccharide,and Na⁺,K⁺and Ca²⁺had no effect on the viscosity of theλ-type red algae polysaccharide.（4）The static rheological experiment results of three red algae polysaccharide forming fluids showed that the three kinds of red algae polysaccharide colloids ofκ,ιandλwere all pseudoplastic fluids,and the melting points were all lower than 60°C,which met the requirements of dipping-glue temperature.（5）Film formation of three red algae polysaccharides:Using gelatin film as a reference product,three different types ofκ,ι,λred algae polysaccharides were separately formed into films and a composite film ofκ,ιred algae polysaccharide was formed.The tensile strength,elongation at break,water vapor transmission rate,and film transmittance were measured as the film properties.The data showed that the film forming properties of the three models were weaker than gelatin,whilecomposite film ofκ,ι-red algae polysaccharide and the gelatin film had similar tensile strength,elongation at break,water vapor transmission rate and film transmittance.The composite film had the feasibility of film formation.PartⅡ:The preparation process of red algae polysaccharide plant pH-position-release hollow capsules was completed and the research results were as follows:（1）Preparation of gastric-soluble hollow capsules:Different ratios ofκandιred algae polysaccharides,glycerol,starch and KCl were used to investigate the sol viscosity and encapsulation data in response to the surface test method.The ratio of the best prescription materials was:κ:ι:modified starch:KCl:Glycerin=1.25:1.45:12:0.27:3.0;The best technical procedure was:The raw materialκ-type red algae polysaccharide,ι-type red algae polysaccharide,modified starch,KCl according to the prescription was weighted,mixed well,and then added water.The sol was formed by heated and stired,and the glycerin was added and then kept warm.After the sol was in a translucent and uniform state,then the squeezing,drying,cutting and arranging can be carried out.The holding temperature was 55℃,the holding time was 1.5 h,the optimum mashing temperature was60℃,and the drying time was 3h.（2）Preparation of enteric hollow capsules（pH 6.8）:The preparation ratio of the small intestine enteric hollow capsules optimized by the response surface test method wasλ-type red algae polysaccharide:sodium alginate:modified starch:gellan gum:glycerol=0.585:3.06:12:0.814:2.0.The process steps were:λ-type red algae polysaccharide,sodium alginate,modified starch,gellan gum were weighed according to the prescription amount,and were mixed.Then water was added.The time of heat and stir was 0.5h.Glycerin was added to the glue and thenthe glue was keeped warm at 55℃for 1.5h.The capsule shells can be obtained by glue,drying and cutting.The optimum process conditions by single-factor method were that the temperature of the gelatin 55℃,and the drying time 3 h.（3）Preparation process of enteric hollow capsules（pH 7.8）:The stomach-soluble red algae polysaccharide hollow capsule and the enteric material were further developed into the colonic enteric hollow capsules by the gelatinization method.The optimal recipe was:polyacrylic resin II:polyacrylic resin III:Tween 80=5:5:6,the solvent is a mixture of ethanol and acetone（1:1）;the gel time is 8-10s,and the drying time is 30min.（4）Scanning electron microscopy showed that the surface and cross section of the stomach-soluble and enteric-soluble hollow capsules which films had a smooth surface,compact structure.and indicated that theκ,ι,λred algae polysaccharide and each auxiliary material had good Compatibility.Part Ⅲ:Study on the quality of plant pH positioning release hollow capsules and its applicationThe gelatin hollow capsules were used as control.The prepared pH-released red algae polysaccharide hollow capsules were used to study the quality of hollow capsules.The effects of the new hollow capsule shells on different properties of the model drugs were investigated.（1）The data of hollow capsules in appearance,capsule thickness,tightness,friability,moisture,weight difference,disintegration time limit,heavy metal examination and microbial limit were investigated.The results showed that three kinds of pH-localized release red algae polysaccharide hollow capsules had colorless and transparent.Tightness and friability of plant hollow capsules were consistent with gelatin hollow capsules.The water content was evenly distributed between 9-11%,less than gelatin hollow which was 12.86%.The average disintegration time of each type capsule shells were:15 min of gastric-soluble capsules in gastric juice,7 min of the small intestine enteric hollow capsules in enteric juice after gastric juice,8.5 min of the colonic enteric hollow capsules in colonic juice after gastric juice and intestinal fluid.It remained intact and was in colonic fluid.The hollow capsules of the experimental capsules had lower levels of heavy metals than gelatin hollow capsules.（2）The stability experiment of the new red algae polysaccharide hollow capsules was carried out.Through the experiments on the effects of high temperature,high humidity and strong light,the prepared new hollow capsules were obtained that appearance,tightness,friability,the moisture and disintegration time limits were consistent with the newly produced hollow capsule data.The red algae polysaccharide hollow capsule had stable quality and was not affected by temperature,humidity and light.（3）Application of red algae polysaccharide hollow capsules in different soluble drugs:The water-soluble drug metronidazole and the poorly water-soluble drug levofloxacin were used as model drugs to prepare gastric-soluble and enteric-coated capsules respectively.The commercially available metronidazole capsules and levofloxacin capsules were used as gastric-soluble reference control.The dissolution rate was between 90-110%,which indicated that the dissolution effect of the prepared metronidazole and levofloxacin capsules and the corresponding commercial gelatin capsules were similar.The enteric hollow capsules can be used to prepare the metronidazole and levofloxacin enteric capsules.After 10 days of high temperature,high humidity and strong light test,the appearance of the capsules was basically unchanged,and the dissolution rate was consistent with the 0-day data.The prepared red algae polysaccharide pH positioning release hollow capsule can be applied to the preparation of water-soluble,water-insoluble drug capsules.（2）Application of red algae polysaccharide hollow capsules in different acid-base drugs:The weakly basic drug omeprazole and the acidic drug amoxicillin were selected to prepare capsules of red algae polysaccharide as capsules,and compared with commercially available capsules.The results showed that the self-made capsules and the commercially available capsules’indexes of appearance,drug content and dissolution rate of capsules prepared under high temperature,high humidity and light conditions were basically same,indicating that the pH-released hollow capsules of red algae polysaccharide were not sensitive to filling acidic and alkaline drugs,and can be used for different acids and alkaline drug capsules.In summary,the gastric-soluble and enteric-type red algae polysaccharide pH-positioning hollow capsules developed by the subject can be applied to water-soluble and water-insoluble,acid-base drugs.This type of hollow capsules expands the application field of red algae polysaccharides,especially for the national use of gelatin as a capsule for different beliefs,providing a reliable basis for the industrial production of pharmaceutical capsules.