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OBJECTIVE: To investigate and compare the dissolution behaviors of diclofenac sodium enteric-coated tablets from Beijing Novartis, Turkey Novartis and German Novartis respectively. METHODS: According to the dissolution test METHODS: in Chinese Pharmacopoeia, the dissolution curves of the preparations in various media were investigated. Whether the dissolution stage in acidic medium has influence on the dissolution behavior as well as the influence of the ionic strength of buffer medium were investigated. RESULTS: The dissolution curves of diclofenac sodium enteric-coated tablets in media of pH 1.0, 5.5, 6.0 and 6.8 could be used as the characteristic dissolution curves of the preparation. The dissolution behaviors of the three preparations after being dissolved in acidic medium for 2 h were similar; the dissolution behaviors were quite different without the dissoulution stage in acid medium; the larger the ionic strength of the buffer medium was, the faster the dissolution rate of the enteric coated tablets was. CONCLUSION: The dissolution behavior of diclofenac sodium enteric-coated tablets depends on the dissolution rates of the enteric coating and the tablet core. The RSD of the dissolution rate just after the formulation starts to dissolute is large; the dissolution phase in acidic medium and the ionic strength of the buffer medium has influence on the dissolution behavior. There is difference in the in vitro dissolution behaviors of diclofenac sodium enteric-coated tablets from manufacturers in different areas of the same group. This study may provide data support for the selection of multi-source reference preparations in the evaluation of generic drug conformance, and plays an important role in guiding the prescription screening and bioequivalence risk assessment.
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OBJECTIVE: To investigate the permeability of diclofenac sodium(DS)through parallel artificial membrane, and compare the differences in the dissolution rates and fluxes of diclofenac sodium enteric-coated tablets from Novartis in Beijing, Turkey and Germany.METHODS :The permeation of diclofenac sodium in different pH media was studied and determined.The effects of excipients on the permeability of diclofenac sodium were investigated by comparing the differences in the permeability of diclofenac sodium enteric-coated tablets.After being placed in acidic media of pH 6.0 and pH 6.8 for 2 h, the difference in the dissolution profiles and membrane fluxes of three sources diclofenac sodium enteric-coated tablets were determined and compared. RESULTS: The permeability of diclofenac sodium in pH 5.0-6.8 medium increased with the decrease of pH value, which was the smallest in pH 6.8 medium (1.08×10-4 cm•s-1). The excipients did not affect the permeability of the main component. The dissolution rate of the sample from Turkey Novartis was slightly faster than those from Beijing and Germany Novartis. CONCLUSION: The permeability of diclofenac sodium depends on the pH of the medium. The biopharmaceutics classification system(BCS) of diclofenac sodium is classified as class Ⅱ, a drug of low solubility and high permeability. The dissolution of diclofenac sodium enteric-coated tablets depends on the dissolving rate of the enteric-coating and the dissolution rate of the tablet core.The dissolution behaviors of diclofenac sodium enteric-coated tablets from different regions of the same company in pH 6.0 and pH 6.8 media are difference but the membrane fluxes are similar. This study may provide data support for the selection of multi-source reference preparations in the evaluation of generic drug conformance, and plays an important guiding role in prescription screening and bioequivalence risk assessment.
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Objective To study the application value of methadazine enteric-coated tablets in the treatment of steroid resistant severe ulcerative colitis.Methods 110 cases of patients with steroid resistance severe ulcerative colitis in our hospital from June 2015 to December 2016 were randomly divided into experimental group and control group (n=55).The control group was given bacillus subtilis duplex living bacterium enteric capsules,the experimental group was given methadazine enteric-coated tablets.The total effective rate, Mayo score, cytokine levels change, C-reactive protein and erythrocyte sedimentation rate were Compared between two groups.Results The total effective rate of the experimental group was 96.36% higher than that of the control group 85.45%(P< 0.05).The Mayo score of the experimental group was (3.17±2.03)and the control group was (3.69±1.97), the difference was not statistically significant.The levels of IL-8、TNF-α in the experimental group were(17.33±2.18) pg/mL ,(18.33±2.23) ng/mL,which were significantly lower than the those of the control group (25.33±2.18) pg/mL, (25.93±1.54) ng/mL (P<0.05).The C-reactive protein in the experimental group was (10.33±2.11) mg/L the ESR (22.39±5.33) mm/h,which was significantly lower than that of the control group (27.27±3.97) mg/L, (33.17±4.93)mm/h (P<0.05).Conclusion Mesalazine is effective in the treatment of steroid resistant severe ulcerative colitis,which can effectively control the inflammation,,reduce the level of IL-8 and TNF-α, worthy of clinical promotion.
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OBJECTIVE:To establish a method for content determination of thymosin α1 in Thymopolypeptides enteric-coated tablets.METHODS:HPLC-MS/MS method was adopted.The determination was performed on Luna C18(2) with mobile phase consisted of 0.1％ formic acid-acetonitrile (gradient elution) at the flow rate of 0.7 mL/min.The column temperature was set at 30 ℃,and sample size was 20 μL.ESI was used with ion spray voltage of 4.5 kV,sheath gas flow rate of 60 arb,aux gas flow rate of 30 arb,sweep gas flow rate of 10 arb and capillary temperature at 320 ℃.The working mode was positive ion monitoring mode.RESULTS:The linear range for thymosin α1 was 1-1 000 ng/mL (r=0.999 9).The limit of quantitation was 1 ng/mL.The limit of detection was 0.1 ng/mL.RSDs of precision,stability and reproducibility tests were all lower than 2.0％.The recoveries were 95.0％-98.0％ (RSD=1.2％,n=6),respectively.CONCLUSIONS:The method is simple,rapid,sensitive and accurate,and can be suitable for simultaneous determination of thymosin α1 in Thymopolypeptides enteric-coated tablets.
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OBJECTIVE:To a evaluation method for the measurement uncertainty for the content of Bisacodyl enteric-coated tablet. METHODS:HPLC external standard method was conducted for content determination of Bisacodyl enteric-coated tablet, and mathematical model for uncertainty evaluation was established to systematically analyze and evaluate the influential factors in processes of solution preparation and instrument measurement. RESULTS:HPLC external standard method showed the content was 97.8%,confidence probability was 95%,expanded uncertainty was 2.8%,and determination result was (97.8 ± 2.8)%,k=2. CONCLUSIONS:The established method is suitable for the evaluation of measurement uncertainty for the content of Bisacodyl en-teric-coated tablet. Regularly calibrated verification for HPLC equipment and strict control of the weighing process will help to im-prove the accuracy measured by HPLC.
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OBJECTIVE:To establish a method for the determination of related substances in bisacodyl raw material and enteric-coated tablet. METHODS:HPLC was performed on the column of Hibar C18 with mobile phase of acetonitrile-20 mmol/L ammonium acetate (acetic acid adjust pH to 5.0)(55∶45,V/V),detection wavelength was 265 nm,flow rate was 1.0 ml/min, column temperature was 30℃,and the injection volume was 20 μl. RESULTS:The linear range of bisacodyl was 0.25-5.0 mg/ml (r=0.999 9);the limits of detection and quantification were 19-25 ng and 61-68 ng for bisacodyl and impurity A,B,C,D and E;RSDs of precision,stability and reproducibility tests were lower than 2%;recovery was 99.50%-101.00%(RSD=0.5%,n=9). CONCLUSIONS:The method is specific, sensitive and reproducible, and can be used for the determination of related substance in bisacodyl raw material and enteric-coated tablet.
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OBJECTIVE:To observe the efficacy and safety of weifuchun tablet combined with rabeprazole enteric-coated tablet in the treatment of chronic gastritis with reflux esophagitis. METHODS:894 gastritis patients with reflux esophagitis were random-ly divided into control group (407 cases) and observation group (487 cases). Control group was given 10 mg Rabeprazole enter-ic-coated tablet,once a day;observation group was additionally given 1 440 mg Weifuchun tablet,orally,3 times a day. The treat-ment course for both groups was 4-8 weeks. Clinical efficacy,microscopic examination grading,total symptom scores,self-rating anxiety scores(SAS),self-rating depression scores(SDS),quality of life scale score(QOLS),Memorial University of Newfound-land Scale of Happiness score(MUNSH) of reflux esophagitis before and after treatment,and incidence of adverse reactions in 2 groups were observed. RESULTS:The total effective rate in observation group was significantly higher than control group,the dif-ference was statistically significant(P0.05);after treatment,the micro-scopic examination grading cases in 2 groups were significantly superior to before,observation group was superior to control group,total symptom scores,SAS and SDS scores were significantly lower than before,observation group was lower than control group,QOLS and MUNSH scores were significantly higher than before,observation group was higher than control group,the dif-ferences were statistically significant(P0.05). CONCLUSIONS:Weifuchun tablet combined with rabeprazole enteric-coated tablet has better efficacy than only rabeprazole in the treatment of chronic gastritis with reflux esophagitis,it can relieve clinical symptoms of pa-tients,with better safety.
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OBJECTIVE:To improve HPLC for the contents determination of 2-methyl-5-methoxy-indole-3-acetic acid(impuri-ty Ⅰ) and 4-chlorobenzoic (impurity Ⅱ) in Indometacin enteric-coated tablet. METHODS:The column was Phenomenex Phe-nyl-Hexyl with mobile phase of 10 g/L acetic acid solution- acetonitrile(gradient elution)at a flow rate of 1.0 ml/min,the detec-tion wavelength was 254 nm,column temperature was 40℃,injection volume was 20 μl. RESULTS:The linear range was 0.262 2-5.243 0 μg/ml for impurity Ⅰ(r=0.999 8)and 0.252 5-5.050 0 μg/ml for impurity Ⅱ(r=0.999 8);the limits of quanti-tation were 1.12 ng and 0.48 ng,limits of detection were 0.340 ng and 0.146 ng,respectively;RSDs of precision,stability and re-producibility tests were lower than 2%;recoveries were 99.71%-100.52%(RSD=0.28%,n=9) and 100.84%-102.14%(RSD=0.47%,n=9). CONCLUSIONS:The method is accurate and rapid,and can be used for the contents determination of impurity Ⅰand impurityⅡin Indometacin enteric-coated tablet.
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OBJECTIVE: To establish a rapid and nondestructive method to determine coating thickness of the total saponin of Radix Bupleuri enteric coated tablets by near infrared spectroscopy (NIRS) analytical technique. METHODS: Spectral pretreating methods, wavenumber selection and factors of NIRS were discussed in detail. Different modeling methods were compared and the methodology of model was investigated. RESULTS: Partial least squares regression (PLSR) was used for building the quantitative calibration model. Correlation coefficients(r), root-mean-squares error of cross-validation (RMSECV), and root mean square error of prediction (RMSEP) obtained by PLSR model were 0.9915, 3.6 and 3.24 μm respectively. CONCLUSION: Predicted results show that the established method is rapid, nondestructive, and reliable, which can be applied to the online monitor of Chinese medicine tablets coating process.
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OBJECTIVE: To reevaluate the bioequivalence of marked metformin hydrochloride enteric-coated tablets. METHODS: Using method 2 described in the appendix X D and apparatus 1 described in the appendix X C in Chinese Pharmacopoeia(edition 2010), the in vitro release of metformin hydrochloride enteric-coated tablets from different pharmaceutical factories (A, B, C, and D) was investigated. The contents were measured by utlraviolet (UV) spectroscopy. Generic tablets from factory A and D were chosen to be test 1 and test 2 preparations, with the innovative metformin hydrochloride tablets (Glucophage) as the reference preparation. In a randomized, three-way crossover study, 21 healthy male volunteers were given a single oral dose of test 1, test 2 and reference preparations containing 500 mg of metformin hydrochloride. Plasma concentrations of metformin were determined by LC-MS/MS. The pharmacokinetic parameters and relative bioavailability were calculated. The bioequivalence between test 1 and reference preparation, test 2 and reference preparation, and the bioequivalence between the two test preparations were evaluated. RESULTS: The in vitro release of metformin hydrochloride enteric-coated tablets from factory B, C and D met the standard of Chinese Pharmacopoeia(the supplement edition of 2010) while that of the tablets from factory A did not. Metformin hydrochloride enteric-coated tablets from factory A and D were chosen to be test 1 and test 2 preparations, respectively. The F0-t and F0-∞ were (72.8 ± 9.7)% and (73.2 ± 10.0)% for test 1 preparation, and (45.5 ± 16.2)% and (46.2 ± 16.0)% for test 2 preparation, respectively. It was failed to conclude that test 1 and reference preparation were bioinequivalent. Test 2 and reference preparation were bioinequivalent, and the two test preparations were also bioinequivalent. CONCLUSION: The bioinequivalence risk of metformin hydrochloride enteric-coated tablets is high. For metformin hydrochloride enteric-coated tablets, not only conducting pre-marketing bioequivalence study with proper reference preparation, but also enhancing post-marketing surveillance and reevaluation of bioequivalence are very important for maintaining the consistency of drugs quality. Copyright 2012 by the Chinese Pharmaceutical Association.
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OBJECTIVE:To study the pharmacokinetics and relative bioavailability of metformin hydrochloride enteric-coated tablets and validate the bioequivalence between the domestic and the imported metformin hydrochloride enteric-coated tablets.METHODS:An oral single dose(1 000 mg)of domestic or imported metformin hydrochloride enteric-coated tablets was given to 26 healthy volunteers in a randomized crossover study.The time-concentrations of metformin hydrochloride were determined by HPLC.The pharmacokinetic parameters as well as relative bioavailability of the domestic tablets were computed.RESULTS:The concentration-time curves of the two kinds of metformin hydrochloride enteric-coated tablets were in line with one-compartment model.The main pharmacokinetic parameters of the domestic vs.the imported metformin hydrochloride enteric-coated tablets were as follows:Cmax(84.9?16.4)?g?L-1 vs.(84.5?13.8)?g?L-1;tmax(0.67?0.07)h vs.(0.77?0.08)h;t1/2 Ke(1.90?0.17)h vs.(1.79?0.19)h;AUC0～t(161.9?16.8)?g?h?L-1 vs.(157.2?19.7)?g?h?L-1;AUC0～∞(179.7?18.2)?g?h?L-1 vs.(173.4?19.2)?g?h?L-1.The relative bioavailability of the domestic enteric-coated tablets was(109.0?7.2)% as against the imported enteric-coated tablets.CONCLUSION:The two kinds of tablets were bioequivalent.
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0.05).It was the same for those of group B.(3)The parameters,T50 and Td,of group A,in comparison with those of group B,showed significant differences(P0.05).There was no significant difference in slope of equation between two groups.CONCLUSION:This measuring method of the in vitro dissolubility of lansoprazole enteric-coated tablets is simple,convenient,accurate,stable,feasible and good in repetition.It is concluded that there is significant difference between the dissolubility of the two dosage forms of enteric-coated preparation of lansoprazole.