| Diterpene lactones Andrographis(A),neoandrographolide(NA),14-deoxy-andrographolide(DA),dehyd roandrographolide(DDA)and any other ingredients are the effective components that exist in Androg raphis effective parts(AEP).As studies shown that it has the pharmacological activities such as antipyretic,anti-inflammatory,anti-tumor and anti-virus,but clinical application is greatly affected by its poor water solubility property and low bioavailability.As a new dosage form of tablets,dispersible t-ablet characterized by rapid disintegration,dissolution rate and high bioavailability.Our team prepare-d the Andrographis effective parts dispersible tablets at the early stage and established its quality standards on the basis of former research and further studied its stability.A method for testing the contents of A、NA、DA、DDA in Andrographis effective dispersible tablets by HPLC are described in this paper.The parameters setup of chromatographic conditions are as follows:chromatographic column:BDS-HYPERSIL,C18 column(250 mm×4.6 mm,5 μm);Column temperature:room temperature;mobile phase: acetonitrile-water gradient,10:90(0 min)→60:40(50 min)→10:90(65min);detection wavelength:205 nm;flow rate: 1mL/min;injection volume:25 μL;theoretical plate numbers were not less than 2000 calculated by andrographolide;trailing factor was between 0.95 and 1.10;the separable degree should above 1.0 between chromatographic peak of standard and adjacent peak.The results showed that A,NA,DA,DDA retention time was 25.729 min,33.423 min,36.003 min,36.640 min.Meanwhile,the regression equations of these four components by methodology are as follows:A:Y=2.2×106X-6.0×105,R~2=0.9997,linear range:2.073 μg-10.365μgNA:Y=2.0×106X-62312,R~2=0.9993,linear range :0.188μg-0.940μgDA :Y=2.9×106X-1.9×10~5,R~2=0.9992,linear range :0.341μg-1.705μgDDA :Y=3.7×106X-3.8×10~5,R~2=0.9994,linear range : 0.581μg-2.905μg.At the same time,the day precision RSD value and inter-day precision RSD value of A,NA,DA,DDA are separate less than 1.82% and 4.71% along with the RSD value of sample solution repeatability are less than 3.64% which all showing that this method is good.The RSD value of sample solution stabilitywithin 48 h is smaller or equal to 4.18% and recovery test in A,NA,DA,DDA,RSD values are 4.37%,2.56%,1.16%,3.62%.Besides,the percentage of effective components of A,NA,DA,DDA in Andrographis effective dispersible tablets are 11.97%,0.55%,1.72%,2.55 %.The quality evaluation of Andrographis effective parts dispersible tablets was carried on according to the《China Pharmacopoeia》(2010 edition).The hardness tester was employed to determine the hardness of Andrographolide effective parts dispersible tablet and the results showed that the pressure is between 40 N and 60 N.Andrographis effective parts dispersible tablets disintegrate within 3min and pass through the 2nd sieve when putting in water of 20℃±1℃ and 100 mL.Meanwhile,the difference between tablet weight is smaller than or equal to 5.0% and weight loss is smaller than or equal to 1% when tested its tablet weight and frangibility which all showing that the Andrographis effective parts tablets comply with regulations of preparation according to the pharmacopoeia.The Andrographis effective parts dispersible tablets are diterpenoid compounds when tested by the method of physical and chemical tests and thin-layer chromatograph.It also showed that control test confirmed its non-interference which indicated its strong specificity.Simultaneously,the heavy metal and arsenic salt in tablets were evaluated by IOES and the results are as follows:Pb content in Andrographis paniculata is 4.0114 mg /kg,concentration is 40.17 ppb;Pb content in Andrographis extract is 0.4536 mg/kg,concentration is 4.5380 ppb;Pb content in Andrographis effective parts dispersible is 0.2867mg/kg,concentration is 2.8730 ppb;As content in Andrographis paniculata is 0.2055 mg/kg,concentration is2.0579 ppb;As content in Andrographis extract is 0.0145 mg/kg,concentration is 0.1451 ppb;As content in Andrographis effective parts is 0.0158 mg/kg,concentration is 0.1583 ppb.We used grouting method to determine the in vitro release profile with 1000 mL 0.3% SDS as the release medium,and the results showed its cumulative release percentage in 30 minutes is more than 95% and the dissolution rate is faster than ordinary tablets.Based on technical guidelines for drug stability,the stablity of Andrographis effective parts tablets was investigated.The impact factors included high temperature test(60℃),high humidity test(25℃,RH90 %±5%)and strong lighting pilot(4500 lx±500lx).The results showed that the trait,identification,dispersion uniformity,moisture,weight variation,content,microbial limit,dissolution of the inspection and other indicators of Andrographis effective part tablet are all standards-compliantin.Nosignificant changes are found in content and dissolution both in accelerated stability test and long-term test which were respectively investigated at the end of 0,Jan,Feb,Mar,Jun and 0,Mar,Jun,Dec.They are all in line with the guiding principles.In summary,Andrographis effective parts tablets are relatively stable,but need be sealed for storage and the ultimate validity are 12 months. |
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