The Fabrication And Characteristics Of Morphine Polyactic-co-glycolic Acid Microspheres

Objective To fabricate morphine polyactic-co-glycolic acid (PLGA) microspheres and study its characters including drug-loading rate, entrapment efficiency, in vitro releasing rate, etc. To observe its pharmacokinetic characters in New Zealand rabbits. Methods Emulsification-solvent evaporation method was adopted to prepare morphine PLGA microspheres. A microscope was used to observe its shape and diameter. A high performance liquid chromatography (HPLC) method was developed to determine the content of morphine in the microspheres. The in vitro releasing rate of microspheres was also investigated and pharmacokinetic equations were matched.16 rabbits were randomized to 4 groups:A, B, C, D. Group A and B received subcutaneous administration of morphine hydrochloride injection (1mg/kg.3mg/kg), group C and D received subcutaneous administration morphine PLGA microspheres(5mg/kg,15mg/kg). The concentrations of morphine in plasma at 5min,10,20,30.40,50,60min,1.5h,2,3,4,6,8,12,16,24h after administration were determined by HPLC. Pharmacokinetic software was used to calculate pharmacokinetic parameter and statistics software was used to do analyzing. Results The microspheres prepared show smooth surface, consistent diameters. The drug loading was about 19.91 mg-g-1 and the embedding ratio was 84.42%. The releasing curves of morphine PLGA microspheres in 5min-4h matched Higuchi kinetics equation, which suggested the diffusion mechanism play a key role in microspheres releasing. The t1/2 (min) of group A is 204.77±35.22, B 162.36±50.9, C 433.77±65.75, D 410.50±54.51, Cmax (μg·mL-1) of group A is 1.39±0.08, B 5.73±0.50, C 0.415±0.01, D 1.11±0.14, Tpeak (min) of group A is 32.5±5, B 30.5±5, C 660±120, D 420±69.28, AUC(min·μg·ml-1) of A is 128.58±16.62, B 309.03±39.86, C 398.96±22.82, D 1172.52±138.87. The t1/2 and Tpeak was prolonged, Cmax was reduced, AUC were greater in Morphine PLGA microsphere groups compared with morphine hydrochloride injection groups, which suggested that morphine PLGA microspheres may be an acceptable controlled-releasing system. Conclusions The morphine PLGA microspheres prepared has characteristics of sustained releasing effection both in vitro and in vivo. The bioavailability enhances and appropriate blood levels of morphine maintains for a prolonged time. As a new drug delivery system, the morphine PLGA microspheres show prospection of more efficient and safer administration.