Study On The Preparation Of Aconitine Smart Hydroel

Aconitine, a C-19diester-diterpenoid alkaloid, is the major components of the Aconitum. It has anti-inflammatory and analgesic activity, and has excellent effect on the treatment of rheumatoid arthritis and other symptoms. But, as for its strong toxicity,0.2mg to poisoning in oral. Smart hydrogel is a new type of drug carrier, having the advantages of reversible response, good water permeability and biocompatibility.The purpose of this paper was to develop a smart hydrogel include aconitine for articular injection and evaluated it. Articular injection administration has drawn much attention recently when it comes to the treatment of rheumatoid arthritis which has a rapid onset, can avoid systemic toxicity and improve drug bioavailability. Poloxamer407, a smart high molecular material, was introduced into articular injection administration. The material can make the hydrogel liquid state at room temperature and a gel formulation when it comes to about37℃at articular. The smart hydrogel preparations have the advantages of the the general articular injection preparation, and can significantly prolong the drug residence time in the joint cavity.The high-performance liquid chromatography (HPLC) method was established to determine the Aconitine concentration. It has the advantages of specific, reproducible, high precision, stability and simple.The properties about P407were studied as an essential part of preformulation. The results indicated that the sol-gel transition temperature of the poloxamer407was in a concentration-dependent manner. And it is different that the drug of aconitine and the formulation additives such as phosphate buffer solution (PBS), glycerol,1,2-propylene glycol and hyaluronic acid effect on the gelation temperature. It provide a basis for designing the formulation of aconitine smart hydrogel.The formulation screening was performed by taking sol-gel transition temperature and in vitro release as indices. The best formulation of aconitine smart hydrogel was aconitine0.05%, glycerol10%,1,2-propylene glycol17%, hyaluronic acid0.20%, P40714.2%,pH5.80PBS as solvent. In this formulation, the sol-gel transition temperature was36.1℃and after96h The in vitro cumulative release rate was89.45%. The in vitro release of aconitine followed Higuchi model.The quality standard of aconitine smart hydrogel was gotten and its stability was investigated. This product was a colorless clear liquid at room temperature and was colorless transparent gel when it was above36.1℃.The formulation was a little unstable to stable heat, so it was better for this preparation to be stored in a place of low heat.The rat articular injection of the aconitine smart hydrogel administration was to assess its irritating. The result indicated that the preparation was non-irritating. The rats which was the animal model of rheumatoid arthritis,15days after modeling, had been administered for3weeks, the conclusion was that aconitine smart hydrogel was effective in anti-inflammatory.The results show that aconitine smart hydrogel which has a anti-inflammatory effect is great potential for intra-articular injection drug delivery system and has a good prospect in the therapeutic efficacy of rheumatoid arthritis clinically.