Research On Alginate Microcapsule As A Controlled Released Carrier Of Lipophilic Drugs

For the mild sol-gel character, good biocompatibility and low market value of the natural macromoleculer material Sodium Alginate (NaAlg or ALG), it is fit to release and encapsulate drugs, albumens and cells. Therefore alginate microcapsule as a drug controlled release system is regarding more and more importance.But now the researches on ALG microcapsule as drug controlled system still have some problems to solve: (1) Now the more mature preparation method is spraying method, but the size of microcapsule made by the method is a little big; meanwhile the process of spraying is one-by-one, so the yielding scale is limited and it can not satisfy the demand of large scale production of drugs. (2) ALG microcapsule is a hydrophilic gel, as a drug carrier, it is easily leaked out encapsulated hydrophilic small molecular drugs, and cause a low encapsulate rate and a short releasing time.Therefore aim at the two problems above, this research is planning to set and optimize a novel emulsification/mtemal gelation method which can be used for large scale production and preparation of small diameter microcapsules, and for the reason that the ALG microcapsule is unfit for small molecular hydrophilic drugs, choose the small molecular lipophilic drug elemene as a model drug to examine its control ability to lipophilic drugs.Methods and Results1. Setting up and optimizing of emulsify/internal gelation methodThe NaALG solution containing insoluble calcium salt was dispersed into the paraffine to form a a W / O emulsion. With continuous agitation, the paraffine contain-ning glacial acetic acid was added into the emulsion, liberating divalent calcium for internal gelation of the alginate polyanions, then the bead was produced.(1) Surfactant Span80 concentration effects on sphericity of gel beads anddistributing of diameters. When the concentration is above 1.5%, good sphericity and a narrow diameter distributing could be get, but a high concentration will low down the yielding rate.(2) NaALG concentration effects on the gel beads' diameter distributing and yielding rate, the best fit rate is 1.5%.(3) Water/oil volume ratio mostly effects on the distributing and diameter of gel beads, when the ratio is bigger, gel bead of a small diameter and high yielding rate will be gained. The best fit water/oil volume ratio is 1:3 to 1:5.(4) The mixing rate is a key factor effecting the diameter distributing of gel beads, enhance the mixing rate could low down the gel beads' diameter and make them distribute together. However a too high speed could low down the yielding rate also. The best fit mixing rate is 200~400rpm.(5 ) Under the optimized conditions, gel beads of diameter distributing mode of223.4um and SPAN value of 0.87 can be prepared. 2. Preparation of elemene-CaALG gel beadThe elemene was dispersed into NaALG solution to form a O/W origin emulsion and then follow the emulsification/intemal gelation method produce elemene-CaALG gel bead. Results are as follows:(1) Generally when forming O/W emulsion, surfactant is needed, but in experiment it was found that surfactant Tween80 could low down the embedding rate and drug load, so Tween80 should not be added.(2) Concentration of NaALG have effects on the diameter distributing, embedding rate and drug load of gel bead, the fitting concentration of NaALG is over 1.5%.(3) The mixing rate is mainly effects the drug loading gel beads'distrabuting. When at a high mixing rate, small diameter gel beads are easier made but it also low down the embedding rate and drug load remarkably, so fitting mixing rate is 300rpm.(4) Water/oil volume ratio also has effects on the diameter of elemene gel beads, but has little effects on embedding rate and drug load. The fitting water/oil volume ratio is 1:5.(5) Drug adding volume mainly effects embedding rate and drug load, the fitting drug adding volume is 0.1g/ml~0.3g/ml.(6) Under the optimized condition, elemene-CaALG gel beads with a 66.4%embedding rate and 13.4mg/m...