Study On Comparing Two Methods Of Preparing Drug Microcapsules Of Eucommiae Ulmoides Oliv

Background:Recently,it has became a hot spot to repair the bone damage as the tissue engineering frame with the calcium phosphate bone cement material.The shortcoming of the solidification calcium phosphorus bone cement is lacking of vesicular structure which benefit for the osteoblast to grow and activeness of bone induction.The Eucommiae ulmoides Oliv(EU)is a traditional Chinese medicine.Previous studys has manifested that the EU extraction has the function to promote bone cell proliferation.It may promote the proliferation and differentiation of osteoblasts and improve the bone inductivity when it was installed in microcapsule and mixed with calcium phosphate bone cement(CPC).Objective:This study prepared the Arabic gum EU microcapsule and chitosan-sodium polymannuronate EU microcapsules using the spray-drying method and the electrostatic method separately,and compared the structures and capability between the two kinds microcapsules. Methods:1.Preparation of EU microcapsule using spray-drying method1.1 PretreatmentMatched wall material solution(Arabic gum andβ-schardinger dextrin mixture allocated proportion 1:1).Then,some EU extraction was weighted and mixed with material solution of wall according to the ratio of 1/10 after dissolved in ethyl alcohol. Then,put to high-pressured homogen processing after heating to 60°C.1.2.Selecting microcapsules preparating conditions:each group set up 5 kinds of preparating conditions separately according to the different feeding current capacity,the temperature and the feeding density,carried on the spray drying to the isotropic pretreatment solution.Efficiency of microencapsulation was determined and the best spray drying condition was selected.2.Preparation of EU microcapsule using electrostatic method2.1 Microcapsule preparationSome EU extraction was put in the beaker and added 1.5%sodium polymannuronate solution,vibrated on the magnetic force mixer,then added to chitosan solution which contains 2%acetic acid(contain CaCl₂)by drops with the static electricity microcapsule generator.Continue stiring for 30min to gain white microcapsules after filtrating and washing.Microcapsules were collected after dried at 50°C or freezing.2.2.Selecting microcapsules preparating conditions:the experiment groups were divided into 3 groups.Group A:1.5%sodium polymannuronate,1.0%chitosan,1.5% calcium chloride conditions are invariable,according to the quantity ratio of sodium polymannuronate and the core material it was divided into 5 subgroups:0.5,1.0,1.5, 2.0,2.5;group B:the quantity ratio of sodium polymannuronate and the core material is 1.5,sodium polymannuronate 1.5%,calcium chloride 1.5%are invariable,it was divided into 4 subgroups according to the chitosan density:0.5%,1.0%,1.5%,2.0%; group C:the quantity ratio of sodium polymannuronate and the core material is 1.5, sodium polymannuronate 1.5%,chitosan 1.0%are invariable,it was divided into 5 subgroups according to the calcium chloride density:0.4%,0.6%,0.8%,1.0%,1.2%. The microcapsules were prepared.Their drug loading and embedding rate were determined.The best preparating condition was screened.3.The EU microcapsules prepared using the spray-drying method and the electrostatic method under the best preparation conditions were taken to compare:3.1 Comparing the apparent morphology of EU microcapsules:the surface structures of microcapsules obtained by different methods were observed using optical microscope and scanning electron microscope.A.observed with optical microscope:products were dispersed with ethanol,ultrasonic vibrated,and then dropped on the slide.B.observed with scanning electron microscope:pasted the EU microcapsules on the SEM sample stage and observed the surface structure.3.2.Comparing the size and distribution of microcapsules:Microscopy analytic method:50 microcapsules were selected in each sample,put on the slide glass,surveyed with vernier caliper on microscope.Microcapsules average diameter and the deviation were got.Compared the size and the distribution of microcapsules of the two methods.3.3.Comparing microcapsules release performance:adopting the first dissolution assay method,calculated the cumulative release media rate of microcapsules at the release of phosphate buffer solution with spectrophotometric determination of aluminum nitrate, and compared the release properties of microcapsules two methods obtained.Results:1.Spray-drying method:at the best conditions of the feeding density 30%,the temperature 150°C,the feeding fluence 25mL/min,it resulted in the particle size for 50.40±2.34um,microcapsule efficiency 93%EU microcapsules.The dry EU microcapsules were yellow powders with not bad smell.The dispersivity and stability were good.The outward appearance of microcapsules were circle entire.The surface was smooth,not obvious pore fold.The granularity was even.The distribution was narrow.In vitro release experiments demonstrated that in the release medium the accumulation release rate of the Eucommia extraction original powder reached to 90% in 2 hours,but that of the EU microcapsule was 63%in 8 hours.2.Electrostatic method:at the best conditions of the quantity ratio of sodium polymannuronate and the core material is 1.5,the chitosan density 1.0%,the calcium chloride density 1.5%,it resulted in the particle size for 200.13±2.21um,carry dosage 15.14%,embedding rate 73.21%EU microcapsules.The EU microcapsules was spherical and white.The outer layer was the semi-permeable membrane and the interior contained the medicine.It turned to white and yellow solid powders with good dispersivity and stability when dried.Microcapsules were circle entire and the surface was smooth.After freeze-drying,the microcapsules surface was not smooth with concave-convex,while the sphere was complete full.The particle size basically distributed between 195²05um.The distribution was very narrow.In vitro release experiments demonstrated that in the release medium the accumulation release rate of the Eucommia extraction original powder reached to 90%in 2 hours,but that of the EU microcapsule was 68%in 8 hours.Conclusions:The surface of the microcapsules spray-drying method obtained was smooth while the electrostatic method obtained was rough and concave-convex.The microcapsule intensity the electrostatic method obtained was not high and relatively easy to distort. The size distribution of the microcapsules both two methods obtained were narrow.The microcapsules size spray-drying method obtained was small,but the electrostatic method obtained was more even.On slow release performance,all microcapsules two methods prepared performed certain slow release function.But the microcapsule structure of spray-drying method was relatively compact.The core material suffusing resistance was big.The slow release performance was better than that of the electrostatic method.It was because chitosan-sodium polymannuronate EU microcapsules have porous structures,through which the core materials can diffuse.