Study On Diclofenac Sodium Solid Dispersion-Chitosan/Sodium Alginate Microspheres

Objective: Under the guidance of the basic theory for pharmacy, Diclofenac sodium ( DS ) solid dispersion (SD) were to delay the DS dissolution. The sustained-release microspheres were then prepared with sodium alginate(SA)and Chitosan(CS)as carriers. In this paper,DS's acting time was prolonged and while side effects were reduced by preparing the microsphere(MS) with SA and CS. The stability and pharmacokinetics were also studied.Methods: (1) The DS analysis method in vitro was established, and physicochemical proterties such as dissociation constants, solubility, and apparent oil-water coefficient were determined.(2) Diclofenac sodium solid dispersion(DS-SD)was prepared using solvent-melt method. Single factor investigation was established to optimize the preparing technology of solid dispersion, and analysized the characters of the solid dispersion. (3) Diclofenac sodium solid dispersion chitosan/sodium alginate -microsphere (DS-SD-CS/SA-MS) were prepared using an emulsion crosslinking technique. The orthogonal design was used to optimize the technology of preparation of microspheres investigated. (4) Pharmacokinetic characteristics of DS-SD-CS/SA-MS were estimated through intragastric administration.Results: (1) The solubility of DS was enhanced with the increasing pH of dissolution medium. (2) Carnauba wax as the lipid carriers showed the best sustained release effect for DS when drug-lipid ratio was 1:4. (3)Entrapment rate and loading amount were taken as indexes, and the optimum conditions were: emulsifier concentration was 0.5g?mL-1, rotation speed for 500 r?min-1, CaCl2 concentration was 0.8 g?mL-1. Micromeritics properties of the microsphere has a good liquidity and in complian with requirements. On this condition, the entrapment rate rate of 23.93% and the loading amount of 3.38% were performed. The average diameter was 112.40μm. The release of diclofenac sodium followed Higuchi's equation in vitro. (4)With intragastric administration,the plasma concentration versus time curve of DS,DS-SD, DS-SD-CS/SA-MS was coincident with one compartment model. Compared to DS, MRT and T1/2 of DS-SD-CS/SA-MS were prolonged and relative bioavailability was 106.4%.Conclusion: DS-SD-CS/SA-MS was an effective sustained-release dosage form.