Study On Optimization Of Preparation And Formulation Of Chitosan Microspheres

Microspheres formulation as a new drug formulations is a hot research direction on the field of pharmaceutical preparations in recent years. Microsphere formulations developed a short history and the technology is not mature enough, thus it has a great potential for development. Microsphere formulation compared to conventional pharmaceutical dosage forms has many advantages, such as masking unpleasant odors and tastes of drugs to improve drug stability, targeting, etc. Chitosan as a natural polysaccharide carrier material has good biocompatibility, chitosan and low toxicity, it is not characterized by hemolysis widely used in pharmaceutical food areas. This paper chitosan as a carrier material, as a model drug enrofloxacin discuss preparation of chitosan microspheres, and the preparation and prescription optimization.Due to the different needs of prescriptions analysis phase and determination of content phase,we establish a UV spectrophotometry and HPLC analysis of the two methods. UV analysis method is mainly used in the screening stage process prescription,it has advantages such as:easy to use,easy to operate, fast; HPLC used for the determination of drug-loaded microspheres, it has the advantage of high accuracy For chitosan microspheres shell is nor easy to destroy, determination accuracy is not high, by comparison of different test methods and summarize the analysis and design of the treatment bath solvent extraction as the determination of the microspheres Orthogonal optimized experimental conditions5%acetic acid solvent volume of800ml, bath temperature80℃, bath time3h. After verification, the microspheres obtained by the solvent extraction bath accurate drug content.Prepared chitosan microspheres by emulsion cross-linking method, because of there are too many factors, firstly, we use single factor test screening and to determine the approximate range of factors:the herbs around5:1, chitosan concentration of2%, compared to the oil phase in water is4:1, stirring speed1000r/min, emulsification time3h, cross-linking time around3h, cross-linking temperature25℃. Then compared against enrofloxacin chitosan microspheres preparation for greater impact water, chitosan concentration, cross-linking time of three factors, the use of composite design response surface methodology to optimize conditions:oil compared water to4.2:1; chitosan concentration of2%; cross-linking time3.5h.. The resulting particle size distribution of microspheres span smaller microspheres round, no adhesions, the average particle size7.21μm, encapsulation efficiency is61.34%, drug loading is70.12%,and the result had good reproducibility. In vitro release test to prove emulsion cross-linked chitosan microspheres prepared by a good slow release.Because the presence of the chitosan microspheres prepared by cross-linking process takes longer, glutaraldehyde has some toxicity and other issues, a new method to design and test new cross-linking agent. Organizations using high shear homogenizer broken system of milk, using the approximate range of transglutaminase as the cross-linkers, firstly,we use single factor test screening and determining factors: the cross-linking PH6, cross-linking temperature at20-40℃, cross-linking time in2-4h, enzyme dosage4g, about the speed10000r/min, homogenized time5-11min. Then the microspheres prepared by cross-linking temperature greater impact, cross-linking time, emulsification speed three factors, the use of composite design-response surface methodology to optimize conditions:cross-linking temperature28℃, cross-linking time3h, emulsification speed10000r/min for the optimum prescription. The resulting average particle size of the microspheres3.95μm, encapsulation efficiency is73.69%,and the result had good reproducibility. In vitro release test to prove emulsifying cross-linked chitosan microspheres prepared with good slow release.The drug-loaded microspheres made of injection-type suspension, with5%concentration of1,2-Propylene glycol as a wetting agent, a1%concentration of tragacanth as suspending agents, through trial and long-term factors experimental verification, preparation the suspension was left for6months, and the contents are then dispersed without decreased, indicating good stability.