| Desvenlafaxine succinate?DVS?is the active metabolite of venlafaxine,it is the new generation of antidepressant drugs.Its mechanism of drug action is serotonin?5-TH?-noradrenaline?NA?reuptake inhibitors?SNRIs?,when compared with the first generation and second generation antidepressants,the treatment efficacy of DVS is significant,which with wide indications,high safety and good tolerance.Desvenlafaxine succinate extended-release tablets was approved by FDA in 2008.The product and related standard has not yet been introduced to domestic market at present,in order to fill the gap,we carried on related research to this preparation.Referring to literature at home and abroad,and combining with a large number of preliminary test,we established the in vitro analysis methods of release,content,content uniformity and related substances of desvenlafaxine succinate?DVS?in extended-release tablets.The release is detected by UV,the content,content uniformity and relevant material was detected by HPLC,all the methods above were systematically validated,and the results showed that the analysis methods were accurate and feasible.Combining with patent information at home and aborad and pre-formulation studies,we selected HPMC as hydrophilic gel skeleton,and we selected direct powdercompression technique according to the physicochemical properties and powder characteristics of drug and excipients.Based on the results of single-factor tests,and referred to the release degree of original development agent,we determined the prescription composition,tabletting process parameters,coating type and the prescription technology,eventually,we obtained the extended-release tablets with smooth surface and good hardness and frangibility,moreover,the slow-release effect is obvious in vitro release test for many times,and had the similar release behavior with original developing agent in four release medium.The content and content uniformity detected by HPLC can both up to the standards;The influencing factors test,accelerated test and long time storage test results wereentirely within the prescribed scope,proving that the prescription of self-made desvenlafaxine succinate extended-release tablets is well with good reproducibility,stable and reliable quality.Pharmacokinetic research: we adopted double cycle double cross experiment design,and determined the concentration of DVS in plasma by LC/MS/MS,then we obtained the 24 h concentration-time curve in vivo after beagle oral self-made tablets and original developing agent,furtherly,we got the in vivo pharmacokinetic parameters by fitting,and the results showed that the AUC0-24 of self-made tablets and original developing agent were?452.89±21.31?and?443.97±44.88?ng·h·mL-1respectively,the Tmax were?2.48±0.30?and?1.91±0.79?h respectively,the Cmax were?38.59±1.81?and?42.53±6.55?ng·mL-1 respectively,and the relative bioavailability of them was?102.96±11.00?%,and all the pharmacokinetic parameters had a ideal t-test results with P>0.05,the result of initial bioequivalence evaluation was good,and the inner quality of preparations was well. |
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