Pharmacology Study Of Morphine Gelatin Microspheres

Part one Preparation of morphine gelatin microsphere and its drug release effect in vitroObjective To explore a way to make morphine gelatin microspheres and study its in vitro releasing characteristics and stability.Methods Morphine gelatin microsphere was prepared with emulsion crosslinking method.Then the recipes and preparation techniques were optimized based on single factor analysis statistical results and orthogonal design.The evaluation parameters were microspheres morphological form,mean diameter,size distribution,drug loadings and the encapsulation efficiency.The in vitro releasing condition of microspheres was investigated.Different statistical models,including Higuchi,Ritger-Peppas, zero order,first order exponential model,were applied to analyze microspheres equation.The stability of microspheres was evaluated under different conditions including high temperature,high moisture and light exposure.Results The optimization of recipes:the proportion morphine and gelatin was 1:2.5;the concentration of span 85 and gelatin were 1.0%and 20%;the dispersion rate was 700 rpm.The results showed that the microspheres produced with the optimized recipes and preparation technique displayed smooth surface,consistent diameters; the mean diameter distribution conformed to the requires;the drug loading was about 20.94%and the embedding ratio was 86.27%.The releasing curves of morphine gelatin-microspheres matched with Higuchi kinetics equation,which suggested the diffusion mechanism play a key role in microspheres releasing.The microspheres were obviously instable under high temperature,high moisture and light exposure.Conclusion The preparation technology of morphine gelatin microspheres is good,which has significant sustained release characteristics in vitro. Part two Pharmacodynamics of morphine gelatin microspheresObjective To explore the pharmacodynamics of morphine gelatin microspheres in rabbits.Methods We determined the analgesic effects of morphine gelatin microsphere on thenar aching model developed in rabbits. Analgesic effect was assessed by cumulative pain scores and pain thresholds. Results Morphine gelatin microsphere had good antalgic effects.,and the the effects were dose-dependent.Conclusion Morphine gelatin microsphere had good analgesic effects.Part three Pharmacokineties of morphine gelatin microspheresObjective To observe the pharmacokinetic characters of morphine gelatin microspheres.Methods After rabbits received subcutaneous administration of morphine and morphine gelatin microspheres,a HPLC method was developed and the concentrations of morphine in plasm at different time were determined. Results Morphine gelatin microsphere afeter s.c.matched with 2-compartment model,and the C_max was reduced,T_max was prolonged;AUC and t_1/2 were greater. The result suggested that morphine gelatin microsphere may be an acceptable controlled-release system.Conclusion Morphine gelatin microspheres exhibit good controlled release properties and maintain relatively constant and sustained plasma concentrations of morphine,which satisfies the demands of design for original new drug delivery system that enhances bioavailability and maintains appropriate blood levels of morphine for a prolonged time.