文献分享 I 自制盐酸羟考酮缓释片在大白兔体内药代动力学与体外释放行为研究

文献

High-performance liquid chromato-graphy （HPLC） method was used to determine the mass concentration of oxycodone hydrochloride in the plasma of New Zealand white rabbits.The chromatographic column was Agilent Eclipse XDB C₈ column （150 mm×4.6 mm，5μm），the mobile phase was 0.005mol/L sodium octanesulfonate solution （containing 0. 5% phosphoric acid，0.2% triethylamine，pH was adjusted to 2.2±0.1 with 50% sodium hydroxide solution）-methanol （750∶250，V/V），the flow rate was 1.5 mL/min，the detection wavelength was 206 nm，the column temperature was 60℃，and the injection volume was 50μL. The in vitro dissolution behavior of and the self-developed preparation and reference preparation of the Oxycodone Hydrochloride Sustained-Release Tablets was investigated by the basket method，flow-through cell method，and reciprocating cylinder method. The cumulative release was calculated，and the in vitro-in vivo correlation （IVIVC） was assessed by the first-order linear regression analysis. Six New Zealand white rabbits were randomly divided into the self-developed preparation group and the reference preparation group，with three rabbits in each group. They were orally administered 40mg of the corresponding drug，and the blood drug concentration time curve was examined within 24.0h. Pharmacokinetic parameters such as peak time（t_max），peak concentration （C_max），area under the plasma concentration-time curve （AUC_0-t），and half-life （t_1/2） were calculated. 

The linear range of oxycodone hydrochloride solution was 0.5-80.0μg/mL （r=0.9997，n=8）. The RSDs of precision and stability test results were lower than 5. 0% （n=3）. The average recovery rates of low -，medium -，and high - quality concentrations of oxycodone hydrochloride solution were 87.83%，91.04%， and 95. 83%，with RSDs of 1.47%，1.33%，and 0. 47% （n=3），respectively. The matrix effects were 95.81%，98.34%，and 105. 48% （n=3），respectively. The results of in vitro release behavior study showed that the basket method，flow-through cell method，and reciprocating cylinder method could achieve sustained and constant drug release，with cumulative release rates exceeding 85% within 8.0h. Among them，the basket method exhibited the highest correlation with the in vivo cumulative absorption curve （r>0.95）. The results of in vivo pharmacokinetic study showed that the t_max，C_max，AUC_0-t，and t_1/2 of the self-developed preparation was （0.50± 0.00）h，（2.40±0.19） μg/mL，（42.33 ± 5. 79）（μg/mL）· h，and （39.71 ± 33.80） h， which were better than （0.67 ± 0.29） h，（2.13 ± 0.53） μg/mL，（30.31 ± 8.78）（μg/mL）· h，and （20. 93 ± 13. 27） h of the reference preparation.