Preparation And In Vivo/in Vitro Release Properties Of Dexamethasone Pellet For Oral Colon-specific Drug Delivery

Objective:Using mixed gel network crosslinking technology between zinc pectin and hydrophobic block material ethylcellulose(EC) and liquid solidification method to prepare dexamethasone pellet for oral colonic-specific drug delivery. Central composite designresponse surface methodology was used to optimize the prescription by calculating the cumulative release in simulated gastro-intestinal medium and pharmacokinetic in rat. The research used bacterial-dependent of pectin to avoid the release of dexamethasone before colon. It provide a new preparation of dexamethasone which is strong efficacy, low side effects and convenient to use.Methods:1、 Preparation of dexamethasone pellet for oral colon-specific drug delivery.On the basis of pectin as a carrier material, ethylcellulose as hydrophobic material zinc acetate as gelling agent and dexamethasone as the model drug the pellets were prepared with the liquid solidification method. Based on the single factor experiment, the best prescription was optimized through central composite design-response surface methodology with conversion value Y=(1-X1)(1-X2)X3 of cumulative release rate in artificial gastrointestinal fluid as index.2、 The evaluation in vitro release properties of pellet.Rotating basket combined with the dialysis bag method was used to evaluate the content of dexamethasone using ultraviolet spectrophotometric method and calculate the cumulative release rate in different medium such as in artificial gastric-intestinal juice 5 h and in artificial colon juice 12 h. Drawing drug release curve to investigate release properties of pellet in vitro.3、 The research in rat pharmacokinetic of drug.Adopt single dose through intragastric method, dexamethasone content in biological samples was detected by HPLC method; draw medicine-time curve on blood plasma, stomach, small intestine, caecum, colon tissue and theirs contents, respectively; deal with the pharmacokinetic parameters with DAS software to evaluate its release properties compared with ordinary tablets in rats.Results:1、 The pellet was yellow, brown, ball, smooth and rounded. The result reveal the best prescription through central composite design-response surface methodology: the concentration of pectin is 0.11 g/m L, the proportion between EC and pectin is 0.37, the concentration of zinc acetate aqueous solution is 0.05 g/m L.2、 Detected by ultraviolet spectrophotometric method, the cumulative release rate of pellets was 19.4 % in artificial gastric-intestinal juice 5 h, and cumulative release rate in colon juice 12 h was 78.1 %.3、 There was obviously delay effect on drug release of pellet in rats. Tmax delay to 8 h and AUC was less a third than ordinary tablets in plasma. Tmax delayed 5 h but AUC is five times more than common tablets in cecum and colon contents and tissue.Conclusion:Using mixed gel network between zinc-pectin and EC as loading drug system, the pellet of dexamethasone for oral colon-specific drug delivery was prepared within the liquid solidification method. It was yellow, brown, ball, smooth and rounded. The release test in vitro showed that pellet had potential colon-specific release properties. Pellet of pharmacokinetic parameters in rat showed that the majority of drug can be conveyed to the colon and released. Therefore, the pellets can achieve targeted release in the colon.