Preparation And Evaluation Of Alginate Enteric-coating Microcapsules Containing Bifidobacteria

In this study, bifidaobacteria-loaded microcapsules were prepared to decrease the destroy of gastric acid and bile acid and improve the survival of bifidobacteria in the gastro-intestinal tract.Alginate microcapsules were prepared loaded with Indomethacin and Paracetamol as hydrophobic and hydrophilic model drug using air atomization technique. The influences of alginate concentration, calcium chloride concentration, air spraying pressure and delivery rate of alginate solution on the particle size were investigated. The influence of drug solubility on the trapping efficiency and loading amount, the relationship of freeze drying time and residual moisture content were also investigated to develop an optimized process. Bifidobacteria-loaded alginate microcapsules were prepared under the process concerned above. Some critical factors which affect the survival of bifidobacteria such as loading amount of bifidobacteria cultures, yeast extracts, antioxidants, cryoprotectants, freeze-drying time and residual moisture content were investigated. And the formulation compositions were optimized according to the survival of the cultures in simulated intestinal fluid for four hours. Then, bifidobacteria-loaded alginate poly-l-lysine microcapsules were prepared. Characteristics of the bifidobacteria-loaded microcapsules were determined and were compared to commercial products.The range of particle size of Indomethacin loaded alginate microcapsules was 86.63± 1.39～103.36±1.28μm. The trapping efficiency of Indomethacinand paracetamol were 50.69%, 0.92%, loading dose were 17.38%, 0.98%, respectively. The residual moisture content of Indomethacin microcapsules were27.08%, 9.59%, 8.49% when freeze drying for 16,20,24 hours, respectively. The results indicated that the size of microcapsules varied with the alginate concentration, spraying pressure and delivery rate of alginate solution,while the calcium chloride concentration affected the size slightly. The trapping efficiency and drug-loading rate were decreased while the solubility of the drug increased. At first, the residual moisture content of microcapsules decreased fast with the freeze-drying time, and changed slightly with the time prolonged. The survival of bifidobacteria-loaded alginate microcapsules can get to 7.59×108cfu/g (in simulated intestinal fluid for four hours), when yeast extract, cystein·Hcl and sucrose were added. Survival of the cultures in microcapsules in simulated intestinal fluid (pH=6.8) for six hours and in simulated gastric fluid (pH=2.0) for 120 minutes were 1.25×109cfu/g and 7.50×104cfu/g, respectively. But the survival of bifidobacteria in the commercial products were less than 103cfu/g. Survival of bifidobacteria loaded in microcapsules has the tendency of decrease when treated with bile acid, but it can maintain at the level of 108cfu/g. To investigate the stability, the microcapsules were stored in a refrigerator at 4℃, the survival ratio of bifidobacteria in one month was 80% and the survival of bifidobacteria was 1.00×109cfu/g.