Research on the preparation and pharmacokinetics of ivabradine hydrochloride sustained-release pellets
Objective To prepare ivabradine hydrochloride sustained-release pellets,and to investigate their drug loading rate,in vitro release and pharmacokinetics in rats.Methods Ivabradine hydrochloride sustained-release pellets were prepared by the fluidized bed coating method.With the drug loading rate as the evaluation index,the process parameters of the drug loading layer were optimized by orthogonal test design;The formulation of sustained-release layer was optimized by response surface methodology.Healthy male SD rats were randomly divided into two groups:ivabradine hydrochloride sustained-release pellets group and ivabradine hydrochloride tablets group.After single administration,the blood drug concentrations were measured at different time points,and the pharmacokinetic parameters were calculated using Das2.0 software.Results The prescription of drug carrier layer:0.75 g ivabradine hydrochloride API,1.80 g hydroxypropyl methylcellulose and 40 g water.The technological parameters of fluidized bed:inlet air volume of 13 m3·h-1,inlet air temperature at 50℃,atomization pressure at 1.2 bar,flow rate of peristaltic pump 0.9 mL·min-1;The formulation of sustained-release layer 7.8% ethyl cellulose,9.1% polyethylene glycol 4 000 and 20% triethyl citrate.The average drug loading rate was 92.4%,and the cumulative release rate was 92.37% after 12 h.The relative bioavailability of ivabradine hydrochloride sustained-release pellets was 135.59% compared with tablets.Conclusion The preparation process of ivabradine hydrochloride sustained-release pellets has good reproducibility,obvious sustained-release effect in vivo and in vitro,and significantly improved bioavailability,which provides a basis for the study of ivabradine hydrochloride sustained-release preparations.
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