Study Of Biodegradable Ethyl Polyglutamic Acid Microspheres

The applications of new biodegradable materials polyglutamic acid (PGA) andits derivatives as drug carriers have caught the pharmaceutical works' attentions inrecent years. Microspheres has the advantage of advanced designing the dosage,controlling release, reducing toxicity of drugs. In this paper, biodegradablemicrospheres were developed using ethyl polyglutamic acid as carrier materials andExemestane as model drug as fo11owing: 1 . Ethyl polyglutamic acid was synthesized with polyglutamic acid byfermentation as material and HCl as catalyst. The effects of catalyst,ratio ofreactants,reaction time and water absorber on the yield of ethyl polyglutamic acidwere discussed . And the optimal conditions are the following : catalyst is5mol.L-1HCl,volume of ethanol is 20mL/gPGA,reaction time is 4-5h,waterabsorber is CaO.The resultant was well liposoluble and its structure was confirmedby analysis of element, UV, IR, H-NMR etc.The degree of substitution is 59.7%; 1Molecular weight is about 24KD by GPC . Good biocompatibility andbiodegradability of ethyl polyglutamic acid were proved by pharmacologicalexperiment. 2.The sustained release microspheres of Exemestane were developed by the o/wemulsion solvent evaporation method using Exemestane as model drug,ethylpolyglutamic acid as encapsulation material,CH2Cl2 as oil phase and gelatin asemulsifier.Drug entrapment and encapsulation rate were detected by dual-wavelengthspectrophotometry.From optical microscope and scanning electron microscope it isobserved that the microspheres were smooth spheres.The conditions of the formationof microspheres were optimized by the central composite design,The effect ofoil/water phase ratio, concentration of encapsulation material, concentration ofemulsifying agent,rotation rate and drug concentration on mean particle size,span,drug entrapment,encapsulation rate and yield were studied.The optimal conditionsare the following: The ratio of oil/water phase is 1/10, the concentration of iiiencapsulation material is 0.4~0.5g.mL-1, the concentration of emulsifier is 0.6% andthe rotation rate is about 1100 rpm.The appearance of the microspheres issmooth. Its particle size distribution is narrow, the 88.80% of the microspheres'diameter are between 9.0~18.0μm,the average particle size is 13.78±3.8μm, the spanis 0.58, the drug entrapment is 14.56%, the encapsulation ratio is 72.20% and theyield is 81.14%. 3.The in vitro drug release behavior of ethyl polyglutamic acid microsphere ofExemestane was studied by dynamic dialysis.The phosphate buffer solution(pH7.4)and 0.5% SDS solution were used as the release medium.The result show:themicrospheres can release continuously 80% drug within 15 d in the pH 7.4 phosphatebuffer solution,T1/2 is 5.5 d,the release profiles followed diffusion-erosionmodel.The feasibility of ethyl polyglutamic acid using as sustained release carrierswas proved.