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    药物研究
  • 药物研究
    WANG Jia;GAO Feng;ZHANG Chun-bing
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    Objective To analyze whether tetramethylpyrazine could protect PC12 cells from injuries induced by caffeine,and to explore the mechanism of tetramethyipyrazine in the treatment of cerebral ischemiareperfusion injury.Methods Caffeine was added to induce apoptosis of PC12 cells.Cytotoxicity was detected by CCK8 assay.The electric potential of mitochondrial membrane was determined by flow cytometry.HMGB1 was detected by Western blotting.Oxidative stress was detected by ELISA.We observed toxicity of caffeine and the protective effects of tetramethylpyrazine.Results After the pretreatment,tetramethylpyrazine significantly improved PC12 cell survival.Mitochondrial membrane potential was increased,the expression of HMGB1 decreased,SOD increased,LDH and MDA decreased,and GSH elevated. Conclusion Tetramethylpyrazine exerts a significant protective effect on PC12 cell injury caused by caffeine.The protective effect may be related to inhibition of apoptosis and regulation of the expression level of mediators involved in inflammation and oxidative stress.
  • 药物研究
    YUAN Hong-yu;WANG Yong-qin;ZHANG Hong-wen;MENG Ling;HAO Kun
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    Objective To investigate the pharmacokinetics (PK) and pharmacodynamics (PD) processes of rabeprazole in inhibiting gastric acid secretion with the combined PK-PD model.Methods A total of 10 healthy volunteers were given a intravenous infusion of 20 mg rabeprazole over a 30min period.The concentration of rabeprazole in the plasma at different time points was detected by HPLC,and the PK parameters were calculated by DAS 2.0 software.At the same time the intragastric pH was monitored over 24 hours to fit the PD parameters with indirect inhibition model.Results The main PK parameters,t1/2,Cmax,and AUC were (60.5±17.3) min,(1 299.1±201.0) ng.mL-1,and (106.4±26.0) mg.min.L-1,respectively.The corresponding PD parameters,Kin,Ke,IC50 and Imax were (8.200±3.362) h-1,(1.080±0.378) h-1,(0.286±0.129) mg.L-1 and (6.93± 2.15) pH,respectively. Conclusion The PK of rabeprazole in healthy volunteers conforms to one compartment model,and the PD fits the indirect response inhibition model.The equation can effectively establish the relationship between the blood drug concentration and the effect.
  • 药物研究
    HUANG Jian-chun;LIU Cong-hui;ZHOU Huan-huan;TAN Li-feng;HUANG Jian-jing;LI Dian-peng;HUANG Ren-bin
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    Objective To investigate the effects of 17-methoxyl-7-hydroxybenzenefurabcgakcone (MHBFC) on isoproterenolinduced ventricular remodeling in mice.Methods Isoproterenol (ISO) was given subcutaneously (1 mg.kg-1,twice per day for 7 d) to induce ventricular remodeling in mice. Mice were divided into normal control group, model group, captopril group, MHBFC low and highdose groups. 65 mg.kg-1 captopril was given by intragastric administration in captopril group, 2.5,5.0 mg.kg-1 MHBFC were given by intravenous injection in MHBFC low and highdose groups. At the end of the 7th day, the hearts of the mice were weighted, and myocardial hypertrophy index was expressed as heart weight/body weight, double kidneys weight/body weight and lung weight/body weight (HW/BW, KW/BW and LW/BW). Colorimetric method was used to determine the content of hydroxyproline (Hyp) in heart, the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in serum. The histological changes were observed by HE and Masson’s staining, the changes of cross section area (CSA), collagen volume fraction, (CVF) and perivascular circumferential collagen area (PVCA) were determined. Results Compared with the model group, MHBFC potently inhibited cardiomyocyte hypertrophy, decreased the HW/BW, KW/BW and LW/BW, improved cardiac pathology changed, increased the of activity SOD, decreased the content of MDA in serum and the content of Hyp in heart tissue (P<0.01 or P<0.05), decreased the CVF and PVCA (P<0.01). Conclusion MHBFC possesses protective effects against ISO induced ventricular remodeling in mice, which may be related to its actions in reducing the oxidative stress and improving the antioxidant activity of the body.
  • 药物研究
    XIA Liang;ZENG Zhen-guo;LIU Pi;ZENG Hao;ZHU Yong;LV Nong-hua
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    Objective To discuss the effects of proteinaseactivated receptor2 (PAR2) agonists on intestinal SIgA levels in rats with severe acute necrotizing pancreatitis (SAP).Methods This study established SAP rat model and observed the levels of TNF-α and IL-6 in intestinal mucosa,SIgA content in intestinal mucus and histopathological changes of intestinal mucosa 6,12,and 24 h after establishment of model.The univariate analysis was used to compare the difference among groups.Linear correlation analysis was used to compare correlation between inflammatory mediators (TNF-α,IL-6) and SIgA content in intestinal mucus,as well as the histopathological scores of intestinal mucosa.Results The level of TNF-α and IL-6 in intestinal mucosa and histopathological scores of intestinal mucosa were all significantly increased but SIgA content was decreased in model group at each time point after establishment of model,as compared with the shamoperated group (P<0.05).The level of TNF-α and IL-6 in intestinal mucosa and histopathological scores of intestinal mucosa were all significantly decreased while SIgA content in intestinal mucus increased in pretreatment group at each time point after establishment of model,as compared with the model group (P<0.05).There was a positive relationship between inflammatory mediators (TNF-α,IL-6) in intestinal mucosa and histopathological scores of intestinal mucosa (P<0.01).There was a negative relationship between inflammatory mediators (TNF-α,IL-6) and SIgA content in intestinal mucus (P<0.05). Conclusion Intestinal mucosa immune barrier was impaired in the early stage of SAP in rats.PAR2 agonist has therapeutic effects on intestinal mucosa immune barrier,which is related to the inhibition of excessive release of inflammatory mediators (TNF-α and IL-6) in rats with SAP.
  • 药物研究
    GONG Zhi-gang;DING Shi-fang;JIANG Qi-jun;FU Wen-bo
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    Objective To investigate the effect of astaxanthin (ASX) on endothelial progenitor cells (EPCs) injury induced by oxidative stress in vitro and to explore its underlying mechanism.Methods Cultured EPCs isolated from peripheral blood were randomly divided into 5 groups: normal control,model group [tertbutyl hydroperoxide (tBHP) 100 μmol.L-1] ,and ASX+tBHP groups (the cells were preconditioned with ASX 0.1,1.0,and 10.0 nmol.L-1,respectively).The cell viability was measured by MTT method.The level of reactive oxygen species (ROS) was determined by DCFHDA method.The changes of mitochondrial membrane potential (MMP) and apoptosis ratio were detected by JC-1 method and DAPI method,respectively.caspase3 activity changes of EPCs were detected.Results The cell viability of EPCs was improved with the increasing concentration of ASX.Compared with the model group [(48.5±4.3)%] ,0.1,1.0,10.0 nmol.L-1 ASX significantly increased the cell viabilities [(57.6±8.2)%,(77.6±7.5)%,and (85.3±6.1)%,P<0.05] .The Results of DAPI staining revealed that ASX pretreatment could significantly reduce the apoptotic rate of EPCs.The apoptotic rate of the model group was (27.8±3.2)%,while that of ASX+tBHP groups was [(20.4±2.9)%,(14.9±1.7)%,and (7.8±0.7)%,P<0.05] ,respectively.The data from caspase3 activity assay indicated that ASX precondition could also remarkably decrease the caspase-3 activity for EPCs.The caspase3 activity of the model group was (0.345±0.018),while that of the ASX+tBHP group were [(0.291±0.013),(0.209±0.004),and (0.169±0.013),P<0.05] ,respectively.In addition,treatment with tBHP resulted in an increase of DCF fluorescence,while ASX precondition could decrease the DCF fluorescence,which suggested the accumulation of intercellular ROS for EPCs.Injury of michondrial membrane resulted in the loss of mitochondrial membrane potential (MMP).The MMP detected by JC-1 method revealed that compared with model group,pretreatment of ASX inversed the reduction of MMP. Conclusion Astaxanthin inhibits endothelial progenitor cell apoptosis induced by oxidative stress through inhibiting ROS production,improving the mitochondrial function and downregulating caspase-3 activity.
  • 药物研究
    LIN Xue-song;XIANG Jun;CAI Ya-na;WANG Le
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    Objective To investigate the protection mechanism of ulinastatin on bacterial endotoxininduced acute lung injury.Methods Acute lung injury was induced by Escherichia colilipopolysaccharide (LPS) 5 mg.kg-1.d-1,intratracheally. Twenty SD rats were randomly divided into control group (n=10) and ulinastatin group(n=10). Ulinastatid group received ulinastatin 50 kU.kg-1,the control groups received the same amount of 0.9% sodium chloride solution.Then the expression changes of rat AQP-1 and AQP-5,alveolar wall thickness change and the degree of pulmonary edema were detected.Results After the injection of LPS into the rat,the expression of AQP-1 and AQP-5 in control group were continuously decreased,but those in ulinastatin group decreased were not obvious. The lung wet/dry weight ratio in the control group increased significantly, the not obvious changes in the ulinastain group. The thickness of the alveolar in 24, 48, 72 h of the control group were (3.84±0.68),(6.32±1.08),(11.03±2.47) μm, respectively, and those in the ulinastian groups were (2.31±0.44),(3.76±0.82),(2.94±0.67) μm, respectively. Conclusion The AQP-1 and AQP-5 induced the occurrence of pulmonary edema by changing the cell permeability.Ulinastatin can slow down the process so as to reduce the degree of endotoxininduced lung injury.
  • 药物研究
    YANG Zeng-yan;ZHOU Hai-song;ZHAO Xiang-pei;TANG Jin;BAI Chun-hui
    Objective To study the acute toxicity of water and ethanol extracts of Radix millettiae speciosae.Methods The maximum tolerated dose (MTD) of water and ethanol extracts of Radix millettiae speciosae were measured for the safety evaluation.Results Maximal tolerated dose (MTD) of water extract was higher than 1 000 g.kg-1,which equaled to 110 times the dose for human adults (60 kg).MTD of ethanol extract was higher than 1 700 g.kg-1,which equaled to 186 times the dose for human adults (60 kg). Conclusion Radix millettiae speciosae does not have obvious toxicity,thus its routine clinical dose is safe and feasible.
  • 药物研究
    WU Ji;CHEN Hui;WU Jian-hong;ZHOU Shun-chang;ZENG Fan-dian
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    Objective To study the effects of pirfenidone on total enzyme and isoenzyme of liver microsomal cytochrome P450 in rats.Methods The activites of liver microsomal dimethyl nitrosamine Ndemethylase (NDMA)and erythromycin demethylase(ERD) were determined. Fiftysix SD rats were randomly divided into six groups, in which they received CMC, dexamethasone 100 mg&#8226;kg-1, ketoconazole 40 mg.kg-1, pirfenidone 25,50,100 mg.kg-1 ,respectively. After administration for 6 and 12 days, livers were prepared liver microsome, the concentration of proteinum in microsome and shade selection to plasma samples were determined by spectrophotometer.Results After administration of pirfenidone for 6 days,cytochrome P450 was significantly increased in 50 and 100 mg.kg-1 pirfenidone groups,as compared with solvent control group (1%sodium carboxymethylcellulose) (P<0.01).After administration of pirfenidone for 6 and 12 days,NDMA of liver microsome was not changed significantly (P>0.05).ERD of liver microsome was significantly increased in 100 mg.kg-1 pirfenidone group after administration for 12 days (P<0.01). Conclusion Pirfenidone can induce P450 and ERD activities in a doseand timedependent manner.
  • 药物研究
    CHEN Mi;CUI Hai-dong;HAO Su-fang;LU Yun;GUO Lian-jun
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    Objective To investigate the effect of daurinoline on basilar artery vascular smooth muscle.Methods The tension of isolated basilar artery ring of rabbit was measured.The effects of daurinoline on the basilar artery contracted by methoxamine,5hydroxytryptamine (5HT),KCl and Histamine (His) were also examined.Doseresponse curves of 5HT and KCl were observed as well.Results Daurinoline exerted obvious relaxation effect on the basilar artery vascular ring contracted by methoxamine,5HT,KCl and His in a concentrationdependent manner.IC50 of daurinoline in methoxamine,5-HT,KCl and Histreated rabbits was 8.67×10-5,1.78×10-6,6.79×10-7 and 4.98×10-4 mol.L-1,respectively.The change of concentrationresponse curves of methoxamine,5-HT,KCl and His showed that daurinoline was a noncompetitive antagonist. Conclusion Daurinoline exerts marked relaxation effect on basilar artery of rabbits through non competitive antagonism.The mechanism of relaxation action may be related to blockage of voltagedependent or receptordependent calcium channels.
  • 药物研究
    TIAN Ren-jun
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    Objective To study the antibiotic activities of leaf extract of Stellera chamaejasme L on the skin.Methods Activities of the leaf extract on Trichophyton gypseum and Staphylococcus aureus was examined by antibiotic susceptibility paper disk method and tube double dilution method.Results When extracted by 95%ethanol,the extract from Stellera chamaejasme L at 100 mg.mL-1 formed an inhibition zone with the diameter of 12.8 mm for Staphylococcus aureus and 12.0 mm for Trichophyton gypseum.When extracted by dichloromethane,the minimum inhibitory concentration (MIC) of the extract from Stellera chamaejasme L was 0.25 mg.mL-1 for Staphylococcus aureus and 0.50 mg.mL-1 for Trichophyton gypsem. Conclusion Leaf extract of Stellera chamaejasme L has an antibacterial activity against Staphylococcus aureus and Trichophyton gypseum and the antibacterial activity against Staphylococcus aureus is stronger.
  • 妇产科用药专栏
  • 妇产科用药专栏
    TONG Ming;CHEN Ying;WANG Jing
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    Objective To evaluate the optimal dosage of misoprostol administered in the rectum for dilation of the cervix.Methods Two hundred and forty women at 40-60 day gestational age without vaginal delivery history were randomly divided into three groups,with 80 cases in each group.Patients received 200,400 or 600 μg of misoprostol rectally one hour before electrical vacuum abortions in group A,B and C,respectively.Cervical dilation,blood loss,and drug side effects in the three groups were compared.Venous blood samples were taken before vein anesthesia,and misoprostol acid concentration in the serum was tested by liquid chromatography-mass spectrometry.Results The analgesic rate was 100.00%in all three dose groups,and cervical dilation rate was 23.75%,46.25%and 70.00%in groups A,B and C,respectively.The severity of drug side effects such as vaginal bleeding and abdominal pain is dosedependent.Blood concentration of misoprostal acid was (117±65),(206±98),and (303±149) pg.mL-1,in groups A,B and C,respectively. Conclusion The recommended dose of misoprostol is 400 μg administered in rectum.Rectal administration of misoprostol is cheap,safe,and convenient,and therefore could be widely applied.
  • 妇产科用药专栏
    TAN Xiu-qun;QIU Ying;HUANG Ying;TANG Zhi-li;MO Feng-mei
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    Objective To compare in vitro fertilization and embryo transfer (IVFET) outcome of gonadotropinreleasing hormone (GnRH) antagonist protocol and GnRH agonist long protocol in patients with polycystic ovary syndrome (PCOS) and to provide reference for rational selection of ovulation stimulation protocol for PCOS patients.Methods One hundred and four patients with PCOS who underwent IVFET were randomly divided into two groups.In the study group,41 patients were subjected to the GnRH antagonist protocol;In the control group,63 patients were subjected to a long protocol of GnRH agonist.Doses and duration of gonadotropin therapy,the thickness of endometrium and the profile of hormone level on the day of HCG administration,the number of retrieved oocytes,the ratio of fertilization,the ratio of cleavage,the ratio of the good quantity embryos,implantation rate of embryo,pregnancy rate,the cycle cancellation rate and the incidence rate of ovarian hyperstimulation syndrome (OHSS) were recorded.Results The IVFET outcome of the two groups was similar with respects to the number of oocytes,the ratio of fertilization,the ratio of cleavage,implantation rate of embryo and the pregnancy rate (P>0.05).Significant differences were found (P<0.05) between the two groups regarding to the doses and duration of gonadotropin therapy,the levels of serum E2 and LH on the day of HCG administration,and the cycle cancellation rate.The incidence rate of OHSS was not significantly different (2.44%vs.12.70%) between the two groups. Conclusion The duration of gonadotropins administration,the cycle cancellation rate,incidence of OHSS and the financial burdern are reduced in patients treated with GnRH antagonist.The growth of follicle,the ratio of fertilization,the ratio of cleavage,implantation rate of embryo and the pregnancy rate are not different between the two Methods .The GnRH antagonist protocol is optimal for patients with PCOS.
  • 药物与临床
  • 药物与临床
    DU Pei;WANG Yi-feng;ZHANG Xiao-wei;CHEN Li-quan;CHEN Guo-qin
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    Objective To investigate the association of ERCC1 and BRCA1 gene expression with clinical features and sensitivity to platinumcontaining chemotherapy in patients with ovarian epithelial carcinoma.Methods Primary ovarian epithelial carcinoma tissues were harvested from 48 patients receiving staging surgery or cytoreductive surgery.Expression of ERCC1 and BRCA1 in the tumor samples was detected by immunohistochemistry.Results ERCC1 expression was correlated with clinical stage (P<0.05) but not with age,pathological type or degree of differentiation (P>0.05).BRCA1 expression was not correlated with any of the clinicopathological features (P>0.05);ERCC1 expression was significantly higher in drugresistant tissues than in drug-sensitive samples (P<0.05);The expression of ERCC1 and BRCA1 was positive in 89.58%and 25.00%of the samples,respectively. Conclusion ERCC1 gene expression is correlated with clinical stage but not with age,pathological type or degree of differentiation.BRCA1 gene expression is not correlated with clinicopathological features.ERCC1 has high positive expression in epithelial ovarian cancer and is correlated with sensitivity of platinumcontaining adjuvant chemotherapy.
  • 药物与临床
    CUI Wei;ZANG Li-min;WANG Long-an
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    Objective To evaluate the effect of atorvastatin on human carotid plaque by high resolution nuclear magnetic resonance imaging (MRI 3.0T).Methods Forty patients with carotid artery plaque were treated with atorvastatin at the dose of 20 mg daily for one year.Changes of the artery plaques were observed by MRI,and the levels of blood lipoproteins and C reactive protein (hsCRP) were detected.Results After the treatment with atorvastatin for 6 months and 1 year,the number and average thickness of plaques were reduced.One year after the treatment,average thickness of stable plaques dropped from (2.41±0.54) mm to (2.17±0.49) mm,and the size of the unstable plaques decreased from (2.38±0.89) mm to (2.01±0.32) mm,with significant differences (P<0.05).The levels of TC,TG,LDLC and HsCRP were significantly decreased (P<0.05) and the level of HDLC was increased. Conclusion High resolution nuclear magnetic resonance (MRI3.0T) can clearly display the components of the atherosclerotic plaque and the degree of artery stenosis.Atorvastatin exerts a significant effect on carotid plaque by promoting the regression of the carotid atherosclerosis plaque.
  • 药物制剂与药品质量控制
  • 药物制剂与药品质量控制
    SHUAI Fang-wen;ZHANG Jia-wei;WANG Xiang-feng;ZHANG Ting;WANG Yu-tong;ZHOU Hong-hao
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    Objective To establish a capillary gas chromatography (GC) method for the determination of residual organic solvents in poly (lacticcoglycolide) (PLGA), including methanol,acetone,dichloromethane,and toluene.Methods A capillary GC method was carried out.DB624 capillary column (30 m× 0.32 mm,1.80 μm) with programmed temperature chromatography was employed.The initial temperature was kept at 40 ℃ for 8 min. Then the temperature was raised to 200 ℃ at a rate of 10 ℃&#8226;min-1.The injection port temperature was 180 ℃,and the split ratio was 10:1.The carrier gas was nitrogen.The temperature of FID was set at 250 ℃,and the sample volume was set at 3 μL.Results Four residual organic solvents consisting of methanol,acetone,dichloromethane and toluene in PLGA were completely separated.The linear range of concentration of methanol,acetone,dichloromethane and toluene was within 10.0-50.0 (r=0.999 8),16.7-83.3 (r=0.999 8),2.0-10.0 (r=0.999 3),and 3.0-14.8 (r=0.999 7) μg.mL-1,respectively.The recovery of methanol,acetone,dichloromethane and toluene was 99.9%(RSD=1.5%),100.8%(RSD=0.9%),100.1%(RSD=1.1%) ,and 99.5%(RSD=0.6%),respectively.Six batches of samples met the requirements. Conclusion The method is proven to be sensitive and accurate after the validation.It is suitable for the determination of residual organic solvents in PLGA.
  • 药物制剂与药品质量控制
    DU Hui;XING Cheng;SHI Yong-qiang;DU Guan-hua;LV Yang;
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    Objective To develop the ribavirin purity certified reference material (CRM) which has measurement traceability and high accuracy,and establish an effective method of evaluation.Methods The homogeneity and the stability were checked by differential scanning calorimetry (DSC).High performance liquid chromatography (HPLC) and DSC Methods were used for purity determination of ribavirin.Results Ribavirin showed satisfactory homogeneity and stability.The certified value of ribavirin was 99.5%with an uncertainty of 0.4%(k=2,P=0.95). Conclusion Ribavirin purity CRM obtained in this paper has been proven to be a national primary CRM with high accuracy and traceability,which can be used to validate analytical Methods ,improve the accuracy of measurement data,establish meteorological traceability of analytical Results as well as control the quality of ribavirin in the pharmaceutical industry.
  • 药物制剂与药品质量控制
    CHENG Yue-fa;LAN Jian-fang;REN Xin-ping;ZHANG Jun;XIE Yue-sheng
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    Objective To establish a new quality control standard for danshen capsules.Methods The qualitative identification of danshen capsules was characterized by ultraviolet fluorescence and thinlayer chromatography (TLC).The contents of tanshinone ⅡA,cryptotanshinone,salvianolic acid B,danshensu and protocatechuic aldehyde in danshen capsules were determined by high performance liquid chromatography (HPLC) on a C18 column.The flow rate was 1 mL.min-1,and the column temperature was 35 ℃.Results The HPLC linear ranges of tanshinone ⅡA,cryptotanshinone,salvianolic acid B,danshensu and protocatechuic aldehyde were 2.046-40.92 μg.mL-1,1.482 25-59.29 μg.mL-1,1.502 55-60.102 μg.mL-1,11.49-459.582 μg.mL-1,and 0.617 4-24.696 μg.mL-1,respectively,and r values were 0.999 9.The average recoveries were 99.66%(RSD of 0.91%) for tanshinone ⅡA,99.26%(RSD of 0.88%) for cryptotanshinone,99.09%(RSD of 0.76%) for salvianolic acid B,100.51%(RSD of 0.62%) for danshensu,and 100.62%(RSD of 0.82%) for protocatechuic aldehyde,respectively.The contents of the tanshinone ⅡA,cryptotanshinone,salvianolic acid B,danshensu showed a certain high level in the 3 batches of danshen capsule samples,but protocatechuic aldehyde was low by comparison. Conclusion The HPLC method is proven to be sensitive,accurate,repeatable,and can be used for quality control of the danshen capsules.
  • 药物制剂与药品质量控制
    ZHANG Yi;YUAN Zhong-wen;GUAN Shi-xia;LI Qing-guo;ZHOU Xiang-ping
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    Objective To prepare nifedipine (NF) sustainedrelease pellet tablets, and study of its release behavior in vitro.Methods Soluplus was selected as a carrier to prepare solid dispersion of NF by hot melt extrusion technique (HME),and the ratio of the drug to carrier was 1:1.The samples were validated as the solid dispersion by differential scanning calorimetry (DSC).Extrusionspheronization technique was introduced to prepare NF pellets and EudragitRS 30D was used as the coating material.The NF sustainedrelease tablets were prepared by direct compression of the coated pellets and suitable excipients.Results The release data in vitro proved that the drug release from the tablets was steady and complete over 24 hours. Conclusion The release of NF from sustainedrelease tablets is slow and steady.The method is easy to operate.The in vitro drug release pattern follows firstorder kinetics.