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Changes in structure of oral solid dosage forms (OSDF) elementally determine the drug release and its therapeutic effects. In this research, synchrotron radiation X-ray micro-computed tomography was utilized to visualize the 3D structure of enteric coated pellets recovered from the gastrointestinal tract of rats. The structures of pellets in solid state and in vitro compendium media were measured. Pellets in vivo underwent morphological and structural changes which differed significantly from those in vitro compendium media. Thus, optimizations of the dissolution media were performed to mimic the appropriate in vivo conditions by introducing pepsin and glass microspheres in media. The sphericity, pellet volume, pore volume and porosity of the in vivo esomeprazole magnesium pellets in stomach for 2 h were recorded 0.47, 1.55 × 108 μm3, 0.44 × 108 μm3 and 27.6%, respectively. After adding pepsin and glass microspheres, the above parameters in vitro reached to 0.44, 1.64 × 108 μm3, 0.38 × 108 μm3 and 23.0%, respectively. Omeprazole magnesium pellets behaved similarly. The structural features of pellets between in vitro media and in vivo condition were bridged successfully in terms of 3D structures to ensure better design, characterization and quality control of advanced OSDF.
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OBJECTIVE:To develop a method for simultaneous determination of 8 residual organic solvents in esomeprazole magnesium raw material,including ethanol,ethyl acetate,isopropylenzene,methanol,methylbenzene,2-phenyl-2-propanol,dichloromethane and acetonitrile.METHODS:Capillary GC was adopted.The determination was performed on HP-1 column by programmed temperature.The temperature of injector port was 220 ℃,with flame ionization detector at temperate of 250 ℃,using nitrogen as carrier gas,at the flow rate of 4.0 mL/min,with split ratio of 10∶1 and injection volume of 1 μL.RESULTS:The linear ranges of ethanol,ethyl acetate,isopropylenzene,methanol,methylbenzene,2-phenyl-2-propanol,dichloromethane and acetonitrile were 45.2-904 μg/mL(r=0.999 7),45.5-909 μg/mL(r=0.999 7),9.0-180 μg/mL(r=0.999 8),27.1-542 μg/mL(r=0.999 8),8.7-174 μg/mL(r=0.999 7),9.1-183 μg/mL(r=0.999 4),5.8-115 μg/mL(r=0.999 4),3.7-74 μg/mL(r=0.999 4),respectively.The quantitation limits were 4.5,3.0,1.4,2.7,0.6,3.0,3.9,2.8 ng,and the limits of detection were 2.2,1.0,0.4,1.4,0.3,1.0,2.0,1.4 ng,respectively.RSDs of precision tests were all lower than 2.0％.Only ethanol,methanol and methylbenzene were detected in reproducibility test,RSDs of their peak area were lower than 2.0％.The recoveries were 95.6％-104.9％ (RSD=3.3％,n=9),98.7％-102.0％ (RSD=1.1％,n=9),100.0％-103.1％ (RSD=1.1％,n=9),95.7％-104.4％ (RSD=3.0％,n=9),99.3％-104.4％ (RSD=1.7 ％,n=9),95.6％-102.2％ (RSD=2.6％,n=9),95.1％-103.3％ (RSD=2.6％,n=9),97.5％-103.3％ (RSD =1.7 ％,n =9),respectively.CONCLUSIONS:The method is sensitive and simple,and it is suitable for simultaneous determination of 8 residual organic solvents in esomerarazole magnesium raw material.
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OBJECTIVE:To investigate the clinical efficacy of itopride combined with esomeprazole magnesium in the treat-ment of esophageal motility dysfunction-induced gastroesophageal reflux disease(GERD). METHODS:A total of 100 patients with esophageal motility dysfunction-induced GERD were selected from our hospital during Sept. 2015-Sept. 2016,and then divided into control group and observation group according to random number table,with 50 cases in each group. Control group was given Esomeprazole magnesium enteric-coated tablets 40 mg,po,qd. Observation group was additionally given Itopride hydrochloride tablets 50 mg,po,tid,on the basis of control group. Both groups received treatment for consecutive 6 weeks. Clinical efficacies of 2 groups were observed,and symptom scores,LES resting pressure,liquid and solid swallowing and peristaltic pressure of esopha-geal body were observed before and after treatment. The occurrence of ADR was recorded. RESULTS:Total response rate of obser-vation group was 94.0％,which was significantly higher than 78.0％ of control group,with statistical significance(P<0.05). Be-fore treatment,there was no statistical significance in symptom scores,LES resting pressure,liquid and solid swallowing or peri-staltic pressure of esophageal body between 2 groups(P>0.05). After treatment,symptom scores of 2 groups were decreased sig-nificantly,and observation group was significantly lower than control group,with statistical significance (P<0.05). Compared with before treatment,LES resting pressure of observation group was increased significantly,and significantly higher than that of control group,with statistical significance (P<0.05). Success rate of liquid swallowing increased significantly in 2 groups,and that of observation group was significantly higher than that of control group,with statistical significance(P<0.05). Success rate of solid swallowing,liquid and solid peristaltic pressure of esophageal body(near segment,middle segment and far segment)in con-trol group were higher than before treatment,without statistical significance (P>0.05). Success rate of solid swallowing, liquid and solid peristaltic pressure of esophageal body(near segment,middle segment and far segment)in observation group were signifi-cantly higher than before treatment,and significantly higher than control group at corresponding period,with statistical significance (P<0.05). No obvious ADR was found in 2 groups during treatment. CONCLUSIONS:For esophageal motility dysfunction-in-duced GERD,itopride combined with esomeprazole magnesium can significantly improve clinical symptom,effectively increase LES resting pressure,strengthen esophageal motor function,improve success rate of esophageal swallowing and enhance anti-gas-troesophageal reflux ability with good safety.
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Objective:To establish a method for the content determination of magnesium in esomeprazole magnesium. Methods:The content of magnesium in esomeprazole magnesium was determined by inductive coupled plasma atomic emission spectrometry. Re-sults:The linear range was 10.0-80.0 μg·ml-1(r=0.999 8). The average recovery was 99.55% with RSD of 1.35% (n=9). The detection limit was 0. 000 75 μg·ml-1 and the quantitative limit was 0. 002 5 μg·ml-1 . Conclusion:The method is accurate, sensitive and reproducible, which can be used for the content determination of magnesium in esomeprazole magnesium.
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Objective To evaluate the similarity of dissolution behavior in vitro of self-made and reference listed drug (RLD) of esomeprazole magnesium enteric tablets. Methods The dissolution test method and HPLC method were established according to Chinese pharmacopoeia. The HPLC method was validated according to ICH guidance. The dissolution behavior of the 3 batches of the self-made drug and RLD were compared in dissolution medium of pH 1.2 HCl solutuion, pH 4.5 phosphate buffer, pH 6.8 phosphate buffer, pH 1.2 HCl solutuion (2 h) and pH 6.0 phosphate buffer, pH 1.2 HCl solutuion (2 h) and pH 6.8 phosphate buffer, and purified water with different rotation rates. Results The HPLC validation results for linearity, repeatability, recovery, etc. all met the requirement. The similarity factors F2 between the self-made drug and RLD were greater than 50 in different dissolution mediums. Conclusion The dissolution behaviors of the self-made drug and RLD are similar.
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OBJECTIVE: To prepare compound aspirin and esomeprazole magnesium enteric-coated pellet capsules and evaluate the drug release in vitro/in vivo. METHODS: The aspirin pellet cores were prepared by using extrusion-spheronization method, and the esomeprazole magnesium-containing drug pellets were prepared with fluidized bed. By using fluidized bed coating method, the two kinds of drug-containing pellets were respectively coated with enteric layer to obtain enteric-coated pellets. After determining the loading capacity by measuring drug content, the two kinds of drug-containing pellets were filled into No.1 capsules. In vitro release was evaluated by measuring release percentage. The in vivo release behavior was evaluated by determination of pharmacokinetic parameters in rats. RESULTS: The cumulative release percentage of the two drugs was less than 5% in 2 h in 0.1 mol·L-1 hydrochloric acid solution. The cumulative release percentage of aspirin was more than 70% in 45 min in pH 6.8 PBS and it was more than 80% in 30 min for esomeprazole magnesium. Aspirin was metabolized to salicylic acid in plasma and its main pharmacokinetic parameters were as follows:t1/2=9.47 h, MRT0-∞=14.43 h, tmax=3.00 h, ρmax=51.34 mg·L-1, AUC0-24=703.39 mg·h·L-1, AUC0-∞=860.52 mg·h·L-1. The pharmacokinetic parameters for esomeprazole magnesium were as follows:t1/2=3.72 h, MRT0-∞=7.44 h,tmax=1.50 h, ρmax=2.71 mg·L-1, AUC0-24=11.89 mg·h·L-1, AUC0-∞=13.79 mg·h·L-1. CONCLUSION: The formulation of compound enteric-coated pellet capsules is reasonable, and the preparation technology has good reproducibility. The drug release is located in the intestinal tract, thus esomeprazole magnesium can antagonize the gastrointestinal side effects of aspirin and aspirin can produce better antithrombotic effect.
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Objective To evaluate the similarity of dissolution behavior in vitro of self-made and reference listed drug(RLD) of esomeprazole magnesium enteric tablets. Methods The dissolution test method and HPLC method were established according to Chinese pharmacopoeia. The HPLC method was validated according to ICH guidance. The dissolution behavior of the 3 batches of the self-made drug and RLD were compared in dissolution medium of pH 1.2 HCl solutuion,pH 4.5 phosphate buffer,pH 6.8 phosphate buffer,pH 1.2 HCl solutuion(2 h)and pH 6.0 phosphate buffer,pH 1.2 HCl solutuion(2 h)and pH 6.8 phosphate buffer,and puri?fied water with different rotation rates. Results The HPLC validation results for linearity,repeatability,recovery,etc. all met the re?quirement. The similarity factors F2 between the self-made drug and RLD were greater than 50 in different dissolution mediums. Con?clusion The dissolution behaviors of the self-made drug and RLD are similar.
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OBJECTIVE: To prepare and evaluate esomeprazole magnesium enteric-coated capsules which is compacted by multiple-unit pellet system (MUPS). METHODS: The esomeprazole magnesium enteric-coated pellets were prepared by fluid bed coating technology, and the effects of isolation layer, amont of core, and thickness of enteric-coated film on the quality of the product were e-valuated. RESULTS: The prepared esomeprazole magnesium enteric-coated capsules showed good release behavior in artificial gastric fluid. The dissolution in artificial intestinal fluid was rapid and complete. CONCLUSION: The established process of preparing esomeprazole magnesium enteric-coated pellets is feasible and reproducible, and the product has similar quality with the original preparation. It is expected to be used in the industrial production.
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The present study was an attempt to formulate and evaluate enteric coated tablets for Esomeprazole magnesium dihydrate delayed release multiparticulate to reduce the Gastrointestinal tract side effects.The delayed release multiple units were prepared by using fluid-bed werster technology.These multiple units are selected by seal coating, drug coating and enteric coating.These Esomeprazole magnesium dehydrate were evaluated for assay, acid resistence, drug release,dissolution, Kinetic studies of Innovator and Optimized formulation, Stability studies of Optimized formulation. This study concluded Esomeprazole magnesium dihydrate can be prepared by using combination of polymers studied and we can reduce the GI tract side effects.
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Aims: Stability indicating simultaneous equation method for determination of Domperidone and Esomeprazole Magnesium in capsule dosage form using UVSpectrophotometry. Study Design: A new simultaneous equation method was developed and validated for the determination of esomeprazole magnesium and domperidone in capsule dosage form. Place and Duration of Study: Department of Pharmaceutical Chemistry, Invertis Institute of Pharmacy, Invertis University, Bareilly, Uttar Pradesh during July 2012 to June 2013. Methodology: Simultaneous equation method was performed for estimation of dosage form and degradants. Results: The maximum wavelength (λmax) was found to be 299 nm for esomeprazole magnesium and 287 nm for domperidone. The linearity range was found to be 1-6 μg ml-1 (r2= 0.998) and 5-30 μg ml-1 (r2= 0.999) for esomeprazole magnesium and domperidone, respectively. The value of limit of detection and limit of quantification was 0.116 and 0.386 μgml-1 for esomeprazole magnesium and 0.657 and 2.18 μgml-1 for domperidone, respectively. Forced degradations were carried out under acid, base, thermal, photolytic and oxidative stress conditions. The method was satisfactorily validated as per the ICH guideline. Conclusion: This study shows that the proposed spectrophotometric method is useful for the routine determination of esomeprazole magnesium and domperidone in its combined pharmaceutical dosage form.
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The present study was to prepare and evaluate the floating microspheres of Esomeprazole magnesium trihydrate as a model drug for prolongation of the gastric retention time for oral delivery. EMT is a proton pump inhibitor which acts by irreversibly blocking the (H+K+)-ATPase enzyme system of the gastric parietal cell. Its half life is 1-1.5 hrs. EMT poor absorption may be because of degradation in gastric acid which can be prevented by incorporation of sodium bi carbonate which is a systemic antacid and act as buffer. The EMT floating microspheres were prepared by double emulsion solvent diffusion method by using Ethyl cellulose and different grades of HPMC like K4M, K15M, using Dichloromethane and alcohol solvent systems. EMT Floating microspheres were evaluated for micromeritic properties, particle size, % yield, In-Vitro buoyancy, incorporation efficiency and drug release. The prepared microspheres were found to be spherical and free flowing and remain buoyant for more than 10 hrs and the particle sizes of microspheres were found to be in the range of 67.24±4.57 μm to 106.35±5.67μm. Incorporation efficiency was found in the range of 54.75±3.51to 83.97±2.54. In-vitro release profile of optimized formulations follows first order non-Fickian (Anomalous) release indicates diffusion and dissolution controlled release. FT-IR and DSC studies revealed the absence of any chemical interaction between drug and polymers used. During the stability period selected microspheres were found to be stable with respect to Entrapment efficiency and drug release characteristics.