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Objective To evaluate the release characteristics in vitro, pharmacokinetics in rabbits and in vivo-in vitro correlation of silymarin phospholipid complex microporous osmotic pump controlled release tablets（SM-PC MPOP）. Methods The release characteristics of SM-PC MPOP in vitro were detected by HPLC in the artificial gastric fluid. Six beagle dogs were subjected to double cycle cross control, which were given SM-PC MPOP and Legalon（30 mg/kg）. The concentration of silybin in plasma was determined by HPLC and the data were processed by software. Results The cumulative release rate of SM-PC MPOP in vitro was over 85% in 12 h. The pharmacokinetics in beagle dogs showed that SM-PC MPOP and legalon conformed to double compartment first-order absorption model and the pharmacokinetic parameters were obtained: tmax:（3.2±0.4）and（0.9±0.1）h, Cmax:（0.298 6±0.068 9）and（0.629 9±0.076 5）μg/ml, AUC0→24:（2.996 8±0.583 3）and（2.268 9±0.432 8）h·μg /ml. The relative bioavailability of SM-PC MPOP was（162.21 ± 30.82）%. Conclusion SM-PC MPOP could release slowly, which could increase the relative bioavailability significantly. The correlation between the absorption in vivo and release in vitro was fine（r = 0.839 0）.
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OBJECTIVE:To investigate the in vitro dissolution behavior and in vivo pharmacokinetics of Cinacalcet hydrochloride tablets, and to evaluate its in vivo-in vitro correlation (IVIVC). METHODS:HPLC method was adopted to determine the accumulative dissolution(Q) of Cinacalcet hydrochloride tablets in 8 kinds of medium [pH 1.2 hydrochloric acid solution,pH 2.0 hydrochloric acid solution,pH 4.5 acetate buffer solution,pH 6.8 phosphate buffer solution,water,artificial gastric fluid(SGF),full belly artificial intestinal fluid(FeSSIF),fasting artificial intestinal fluid(FaSSIF)],and the dissolution curves were drawn. HPLC-MS method was used to determine the blood concentrations of Cinacalcet hydrochloride tablets. A total of 12 healthy male volunteers were selected and given single oral dose of Cinacalcet hydrochloride tablets 75 mg under the state of fasting or satiety(high-fat food). The blood concentration of cinacalcet hydrochlorid was determined before medication(0 h)and 0.5,1,2,3,4,6,8,12,24 h after medication. Average blood concentration-time curves were drawn. The in vivo accumulative absorption percentage (F) of satiety group was calculated by using DAS 3.0 software. Linear regression of F with in vitro Q was carried out to analyze its IVIVC. RESULTS:There was great difference among dissolution curves of Cinacalcet hydrochloride tablets in 8 kinds of dissolution mediums. There were differences of AUC0→t,AUC0→∞ and cmax between fasting group and satiety group,with statistical significance(P＜0.05),showing high-fat food had significant effect on in vivo pharmacokinetics. Correlation coefficient of in vivo F in satiety group with in vitro Q of the tablets in FeSSIF was highest (0.977 9),manifesting good IVIVC (class A). CONCLUSIONS:The in vitro dissolution behavior of Cinacalcet hydrochloride tablets in FeSSIF(paddle method,50 r/min)is well associated with its in vivo pharmacokinetics,which can be used for predicting in vivo dissolution and absorption of the tablets.
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In vitro lipolysis model has become a new and promising technique to screen and evaluate oral lipid formula-tions .This model mimics the gastrointestinal tract environment and well reflects the fate of lipid formulations in GI tract after oral administration .This review summarizes the characteristics of lipid formulations ,process of gastrointestinal digestion ,ap-plications of in vitro lipolysis model and methods for the characterization of the lipolysis process ,which provides the basis for the research of oral absorption mechanism and in vivo-in vitro correlations of lipid formulations with lipolysis model .
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OBJECTIVE: To investigate the in-vitro release behavior of venetoclax preparations, the pharmacokinetic processes and the correlations between in-vitro release and in-vivo absorption of venetoclax in Beagle dogs. METHODS: The dissolution curves of venetoclax preparations in different dissolution media were studied. HPLC method was established for the determination of venetoclax in Beagle dogs, and the pharmacokinetics were studied for commercial venetoclax tablets in Beagle dogs under fed and fasted states.The IVIVC study was carried out by linear regression of cumulative in-vitro drug release and in-vivo absorption accumulation percentage data. RESULTS: The in-vitro release behavior among venetoclax formulation in 4 dissolution media were significant difference. The simple, accurate and rapid analysis method for venetoclax blood samples was established. The fed group and the fasted group AUC0→∞ were (32.38±5.87) and (27.70±6.32) mg·h·L-1, the concentration of peak were (4.04±0.78) and (3.72 ±0.69) μg·mL-1, the peak time were (6.01±1.04) and (4.27±0.92) h, respectively, and there was obvious difference (P<0.05) in AUC0→∞ and the peak time between two group. Percentage of in-vivo absorption was in good agreement with in-vitro release in pH 6.8 0.2%SDS media. CONCLUSION: The study shows that food could improve the bioavailability of venetoclax formulation; 0.2%SDS pH 6.8 media (paddle, 75 r·min-1) is the in-vivo release of venetoclax associated with the in-vitro release condition.
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Objective: To evaluate therelease characteristicsin vitro, pharmacokinetics in rabbits and in vivo-in vitro correlation of tectorigenin floating sustained-release tablets (TFSRT). Methods: The release characteristics of TFSRTin vitro was detected with HPLC in the artificial gastric fluid. Six Japanese Giant Ear Rabbits as self crossover control, which were given TFSRT and suspension liquid (200mg). The concentration of tectorigenin in plasma was determined with HPLC and the data were processed with PKsolver 2.0 software. Results:The cumulative releaserate of TFSRTin vitro was over 70% in 10 h.The pharmacokineticsin rabbits showed that TFSRT and tectorigenin suspension liquid conformed to the single compartment model and the pharmacokinetic parameters were obtained: tmax: (2.809±0.371) and (0.442±0.138)h, Cmax: (6.317±1.337) and (9.662±2.759) μg/mL, AUC0-t: (74.156±10.420) and (57.059±13.309) μg∙h/mL. The relative bioavailability of TFSRT was (134.63±27.94)%, so there was significant difference between them. Conclusion: TFSRT can release slowly, so it increase the relative bioavailability significantly. The correlation between the absorption in vivo and release in vitro is fine (r=0.9879), so the release rate in vitro can control the quality of TFSRT.
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The recent study on gastric retenting drug delivery system (GRDDS) used in Chinese medicinal formule has been summaried and overviewed in this paper. The key problems about the development of GRDDS have been explored, the influence about absence of the system for in vivo-in vitro correlation (IVIVC) analyzed, especially the evaluation on IVIVC model discussed, and the possible approach that artificial neural networks (ANN) are applied in GRDDS for Chinese medicinal formule has been put forward. The processing technology, evaluation of IVIVC, and the advantage, characteristic, and problems of the application of ANN have been studied in order to provide the reference for innovating research of Chinese medicinal formule.