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The subchronic toxicity and toxicokinetics of a combination of rabeprazole sodium and sodium bicarbonate were investigated in dogs by daily oral administration for 13 consecutive weeks with a 4-week recovery period. The dose groups consisted of control (vehicles), (5 + 200), (10 + 400), and (20 + 800) mg/kg of rabeprazole sodium + sodium bicarbonate, 20 mg/kg of rabeprazole sodium only, and 800 mg/kg of sodium bicarbonate only. Esophageal ulceration accompanied by inflammation was observed in only one animal in the male (20 + 800) mg/kg rabeprazole sodium + sodium bicarbonate group. However, the severity of the ulceration was moderate, and the site of occurrence was focally extensive; thus, it was assumed to be a treatment-related effect of rabeprazole sodium + sodium bicarbonate. In the toxicokinetics component of this study, systemic exposure to rabeprazole sodium (AUClast and Cmax at Day 91) was greater in males than females, suggesting sex differences. AUClast and Cmax at Day 91 were increased compared to those on Day 1 in a dose-dependent manner. A delayed Tmax and no drug accumulation were observed after repeated dosage. In conclusion, we suggest under the conditions of this study that the no-observed-adverse-effect level (NOAEL) of the combination of rabeprazole sodium + sodium bicarbonate in male and female dogs is (10 + 400) and (20 + 800) mg/kg, respectively. [ABSTRACT FROM AUTHOR]

Aims Clostridium perfringens infections affect food safety, human health, and the development of the poultry feed industry. Anti-virulence is an alternative strategy to develop new drug. Perfringolysin O (PFO) is an exotoxin of C. perfringens that has been demonstrated to play critical roles in the pathogenesis of this organism, promising it an attractive target to explore drugs to combat C. perfringens infection. Methods and results Based on an activity-based screening, we identified six PFO inhibitors from the Food and Drug Administration (FDA)-approved drug library, among which rabeprazole sodium (RS) showed an optimal inhibitory effect with an IC50 of 1.82 ± 0.746 µg ml−1. The GLY57, ASP58, SER190, SER193-194, ASN199, GLU204, ASN377, THR379, and ALA200 in PFO interacted with RS during binding based on an energy analysis and H-bond analysis. This interaction blocked the oligomer formation of PFO, thereby inhibiting its cytotoxicity. RS treatment significantly increased the survival rate and alleviated pathological damage in C. perfringens or PFO-treated Galleria mellonella. Conclusions RS could potentially be used as a candidate drug for treating C. perfringens infection. [ABSTRACT FROM AUTHOR]

Rabeprazole sodium is a widely used drug for gastrointestinal disorders. Several analytical methods for identifying rabeprazole sodium and its impurities have been reported. However, the genotoxicity of rabeprazole sodium and its impurities is still unclear. Thus, it is necessary to develop analytical methods that can identify the structures of its impurities and evaluate their genotoxicity. Here, we used high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry for identifying the impurities in rabeprazole sodium enteric-coated tablets. Impurities in the samples were matched with synthesized impurities based on the exact mass and secondary mass spectrometry characteristics and then subjected to in silico analysis using the Derek and Sarah software, as well as in vitro genotoxicity evaluations. Our method successfully identified the impurities as 2-[[4-(3-methoxy propane)-3-methyl-N-oxido-2-pyridyl] methyl sulfonyl]-1H-benzimidazole (impurity I), 2-[[4-(3-methoxy propane)-3-methyl-2-pyridyl]methyl sulfonyl]-benzimidazole (impurity II), 2-[[4-(3-methoxy propane)-3-methyl-2-pyridyl] methionyl]-1H-benzimidazole (impurity III), and 2-mercapto benzimidazole (impurity IV). In silico analysis predicted that impurity III demonstrated a structural alert; thus, this impurity was evaluated for in vitro genotoxicity using the Ames test and chromosomal aberration assay. Impurity III at concentrations of 7.5–30 μg/mL had an aberration rate of over 5% with or without S-9 mix. Furthermore, impurity III at concentrations of 40–1000 μg/plate significantly increased the number of mutagenic colonies with or without S-9 mix. These results indicated that impurity III should be regulated to the limit of 0.01%. [ABSTRACT FROM AUTHOR]

Clidinium bromide, rabeprazole sodium, chlordiazepoxide and dicyclomine hydrochloride(COLIWIN-R) drug combinations are used for the treatment of gastric acidity, anxiety, intestinal ulcers, abdominal cramps, irritable bowel syndrome and abdominal pain. A high performance liquid chromatographic method has been developed and validated for the simultaneous determination of clidinium bromide, rabeprazole sodium, chlordiazepoxide and dicyclomine hydrochloride in capsules dosage forms using WATERS C18 column (50 mm x 4.6 mm, 5 pm) with mobile phase consisting of methanol, acetonitrile and phosphate buffer 40:30:30 (V/V) (0.05M, pH 4.0 adjusting with 0.5% ortho phosphoric acid) at a flow rate of 1.0 mL/ min monitoring the effluents at 220 nm. The retention times of clidinium bromide, rabeprazole sodium, chlordiazepoxide and dicyclomine hydrochloride in capsule formulation were found to be 2.9 min, 3.5 min, 4.7 min, and 8.0 min, respectively. The method was validated according to the ICH guidelines for specificity, LOD, LOQ, precision, accuracy, linearity, ruggedness and robustness. The method show good reproducibility and recovery with % RSD less than 2. The proposed method was found to be simple, specific, precise, accurate and linear. Hence, it can be applied for routine analysis of clidinium bromide, rabeprazole sodium, chlordiazepoxide and dicyclomine hydrochloride in pharmaceutical combined dosage forms. [ABSTRACT FROM AUTHOR]

The aim of this study was to develop immediate-release oral rabeprazole sodium tablets with rapid efficacy and gastric stability for the treatment of gastroesophageal reflux disease. Rabeprazole sodium is a commonly prescribed proton pump inhibitor; however, it is extremely unstable and degrades in acidic environments. Hence, it has been manufactured and supplied only in enteric-coated tablet form, while immediate-release (IR) formulations for this drug are very limited. In this study, we applied the quality by design (QbD) approach to formulate and optimize an IR dry-coated tablet containing rabeprazole sodium as an inner core with an outer sodium bicarbonate layer to stabilize the active pharmaceutical ingredient at gastric pH. We also investigated the stability of the pharmaceutical dosage form and its pharmacokinetic profile. The results show that the developed tablets are stable for approximately 12 months and have a high dissolution rate, greater than or equal to 90% at 30 min. Further, in vivo beagle pharmacokinetics confirmed that the newly developed IR tablet had an AUCt which is bioequivalent to the existing delayed-release rabeprazole tablet; however, its Tmax was 0.5 h, which is up to seven times faster than that of the existing tablet. Moreover, the IR tablet was found to immediately absorb in the stomach. Hence, the development of IR tablets can be used as a platform to overcome the technical and commercial limitations currently associated with various proton pump inhibitors used to treat patients with gastroesophageal reflux disease that require immediate therapeutic relief.

The aim of present study was to prepare buffered tablets of acid labile drug, Rabeprazole sodium for oral administration using buffering agents to protect a drug from gastric fluid. Rabeprazole belongs to a class of antisecretory compounds (substituted benzimidazole proton-pump inhibitors) that do not exhibit anticholinergic or histamine H2-receptor antagonist properties, but suppress gastric acid secretion by inhibiting the gastric H+, K+ATPase at the secretory surface of the gastric parietal cell. Rabeprazole blocks the final step of gastric acid secretion. The tablets were prepared by direct compression and wet granulation method. The formulations contain water soluble buffers such as sodium bicarbonate and trisodium phosphate as well as water insoluble buffers as magnesium oxide, magnesium hydroxide and calcium carbonate and crospovidone as superdisintegrant. Preformulation studies like angle of repose, bulk density, tapped density, Carr’s index, hausner’s ratios, DSC and drug/excipient compatibility study were conducted and evaluated for hardness, friability, weight variation, drug content, disintegration and in-vitro dissolution. In the present study, pH of F6 batch was found to be optimum and disintegration time is 42 sec. The drug release was found to show maximum drug release in case of F6 with 99.3% in 60 minutes. In case of stability studies study of the optimized batch, all the results were found to be satisfactory and within limits. There were no significant changes after the period of 1 month study. [ABSTRACT FROM AUTHOR]

ABSTRACT: The present research work deals with the development of pH‐responsive hydrogel by free radical polymerization in aqueous media to protect the rabeprazole sodium from acidic environment of stomach. Swelling behavior of hydrogels that was observed in buffer of various pH indicated highly pH‐dependent swelling of hydrogels. Characterization of pH‐responsive hydrogels by FTIR, SEM, and thermal analysis revealed that hydrogel has porous structure, favors swelling, drug loading, and drug release at a specific site in gastrointestinal tract and thermally more stable than parent polymer. In comparison with simple drug solution and hydrogel formulations, pharmacokinetic parameters of hydrogels formulations showed a significant difference in Cmax values of (CMC‐g‐AA) CA and the same oral dose of rabeprazole sodium was 87.28 ± 12.671 and 61.263 ± 5.37 ng/mL, respectively, Tmax of graft copolymer matrices CA (4.43 h) was significantly (P < 0.05) higher than drug solution (1 h) and area under curves (AUCs) for CA (952.25 ± 191 ng⋅h/mL) was significantly (P < 0.05) higher than the drug solution (83.67 ± 8.28 ng⋅h/mL) indicated the effect of dosage form would last for longer duration. Thus, in vitro and in vivo drug release studies of hydrogels proved their controlled release behavior with preferential delivery into alkaline pH environment and for a prolonged period of time. [ABSTRACT FROM AUTHOR]

A polymerized film of eriochrome black T (EBT) was prepared on the surface of pencil graphite electrode in alkaline solution by cyclic voltammetry. The redox response of the poly (EBT) film at the electrode appeared in a couple of redox peak in 0.1 M sodium hydroxide. The poly (EBT) film-coated electrode exhibited excellent electrocatalytic activity towards the oxidation of rabeprazole sodium (RAB sodium) and domperidone (DOM) in Britton-Robinson buffer (pH 4.0). The polymer film modified electrode conspicuously enhanced the redox currents of the cited mixture and could sensitively and separately determine them. Both cyclic voltammetry (CV) and square wave adsorptive stripping voltammetric (SWAdSV) methods were utilized to determine this mixture. The linearity of CV ranged from 4.1-120 μM and 5.2-90 μM for RAB sodium and DOM, respectively while SWAdSV was 7.5-80×10−7M and 5-70×10−7M for RAB sodium and DOM, respectively. With good selectivity and sensitivity, the present method provides a simple method for selective detection of RAB sodium and DOM binary mixture in synthetic mixtures and biological fluids. [ABSTRACT FROM AUTHOR]

Rabeprazole sodium is one of the most effective proton pump inhibitors (PPIs) used in antiulcer therapy. Like most other PPIs, owing to its acid-labile nature, the drug is formulated as enteric-coated dosage form. Conventional means of producing delayed release multiparticulate dosage forms of PPIs require large quantities of enteric polymer coatings. In the present study, in order to better evaluate the effect of polymeric coating on product performance, the pellet core structure and composition was kept constant. Four different enteric-coating formulations and designs were evaluated. Enteric-coated drug multiparticulates prepared with single polymeric coatings (acrylic or cellulosic) were compared with two different polymeric layer coatings to evaluate the effectiveness of latter coatings in more effectively producing a better rabeprazole sodium delayed-release pellet product. The pH-dependent, enteric acrylic, and cellulosic polymers were used either alone, in combination, or applied one over the other to impart delayed-release properties to the core drug pellets. It was demonstrated that dual delayed-release coating with two different enteric polymers-an inner acrylic coating followed by an outer cellulosic coating-yields the best product that provides all the desired physicochemical and drug dissolution characteristics.

Objective To establish a HPLC method for the content determination of Rabeprazole Sodium for Injection. Methods The high-performance liquid chromatography(HPLC) was adopted with 0.01 mol/L dipotassium hydrogen phosphate buffer solution(pH7.0)-methanol(53:47) as the mobile phase, the detection wave length was 284 nm, the flow rate was 1.0 mL/min, the column temperature was 25°C. The content of Rabeprazole Sodium for Injection was detected. Results The rabeprazole sodi um concentration in the range of 19.968-199.680μg/mL has a good linear relationship(Y=21.803 5X-17.373 4, r=1.000 0),the average recovery rates of high, middle and low concentrations (n=9)were 99.9%[relative standard deviation (RSD)=0.08%];the in termediate precision RSD was 0.30%(n=6),the repeatability and durability were good. The contents of 3 batches of Rabeprazole Sodium for Injection (S28-140101, S28-140102, S28-140103) detected by HPLC were 101.3%,99.7%and 100.1%respectively. Conclusion The established HPLC method is simple, sensitive and accurate, which is suitable for the content determination of Rabeprazole Sodium for Injection. [ABSTRACT FROM AUTHOR]

The study was intended to develop a new intra-gastric floating in situ microballoons system for controlled delivery of rabeprazole sodium and amoxicillin trihydrate for the treatment of peptic ulcer disease. Eudragit S-100 and hydroxypropyl methyl cellulose based low density microballoons systems were fabricated by employing varying concentrations of Eudragit S-100 and hydroxypropyl methyl cellulose, to which varying concentrations of drug was added, and formulated by stirring at various speed and time to optimize the process and formulation variable. The formulation variables like concentration and ratio of polymers significantly affected the in vitro drug release from the prepared floating device. The validation of the gastro-retentive potential of the prepared microballoons was carried out in rabbits by orally administration of microballoons formulation containing radio opaque material. The developed formulations showed improved buoyancy and lower ulcer index as compared to that seen with plain drugs. Ulcer protective efficacies were confirmed in ulcer-bearing mouse model. In conclusion, greater compatibility, higher gastro-retention and higher anti-ulcer activity of the presently fabricated formulations to improve potential of formulation for redefining ulcer treatment are presented here. These learning exposed a targeted and sustained drug delivery potential of prepared microballoons in gastric region for ulcer therapeutic intervention as corroborated by in vitro and in vivo findings and, thus, deserves further attention for improved ulcer treatment. [ABSTRACT FROM AUTHOR]

The aim of the present study was to clarify whether gastric antisecretory drugs affect the clinical efficacy and toxicity of orally administered melphalan in patients with multiple myeloma. A total of 10 patients receiving bortezomib plus oral melphalan and prednisolone (VMP) therapy between December 2011 and November 2014 were analyzed retrospectively. The patients were divided into a control group (seven patients) and a concomitant group (three patients, who were also administered with gastric antisecretory drugs). The gastric antisecretory drugs included rabeprazole sodium (two patients) and famotidine (one patient). No significant differences between the groups were observed in either the characteristics of the patients or the VMP regimen. The levels of monoclonal protein (M protein) in the control group tended to decrease (with a VMP cycle-dependency), although they were primarily stable in the concomitant group. During the second and third VMP cycles, the levels of M protein were markedly lower in the control group compared with the concomitant group. All the patients in the control group achieved a partial response, whereas those in the concomitant group exhibited stable disease. Hematological toxicity levels were revealed to be comparable between the two groups, whereas gastrointestinal toxicity was more prevalent in the control group. In conclusion, the results of the present study suggested that the clinical efficacy of melphalan may be reduced by the co-administration of gastric antisecretory drugs. This interaction may result in decreased toxicity and clinical efficacy of melphalan. [ABSTRACT FROM AUTHOR]

Itopride hydrochloride (IT) and Rabeprazole sodium (RB) are co-formulated together for the treatment of gastro-esophageal reflux disease. Three simple, specific and accurate spectrophotometric methods were applied and validated for simultaneous determination of Itopride hydrochloride (IT) and Rabeprazole sodium (RB) namely; constant center (CC), ratio difference (RD) and mean centering of ratio spectra (MCR) spectrophotometric methods. Linear correlations were obtained in range of 10–110 μg/μL for Itopride hydrochloride and 4–44 μg/mL for Rabeprazole sodium. No preliminary separation steps were required prior the analysis of the two drugs using the proposed methods. Specificity was investigated by analyzing the synthetic mixtures containing the two cited drugs and their capsules dosage form. The obtained results were statistically compared with those obtained by the reported method, no significant difference was obtained with respect to accuracy and precision. The three methods were validated in accordance with ICH guidelines and can be used for quality control laboratories for IT and RB. [ABSTRACT FROM AUTHOR]

Three simple, specific and accurate spectrophotometric methods manipulating ratio spectra were developed and validated for simultaneous determination of Rabeprazole sodium (RB) and Domperidone (DP) in their binary mixture without prior separation. Method A, is constant center spectrophotometric method (CC). Method B is a ratio difference spectrophotometric one (RD), while method C is a combined ratio isoabsorptive point-ratio difference method (RIRD). Linear correlations were obtained in range of 4-44µg/mL for both Rabeprazole sodium and Domperidone. The mean percentage recoveries of RB were 99.69±0.504 for method A, 99.83±0.483 for (B) and 100.31±0.499 for (C), respectively, and that of DP were 99.52±0.474 for method A, 100.12±0.505 for (B) and 100.16±0.498 for (C), respectively. Specificity was investigated by analysis of laboratory prepared mixtures containing the cited drugs and their combined tablet dosage form. The obtained results were statistically compared with those obtained by the reported methods, showing no significant difference with respect to accuracy and precision. The three methods were validated as per ICH guidelines and can be applied for routine analysis in quality control laboratories. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To probe into the efficacy and safety of quadruple therapy of rabeprazole in treatment of Helicobacter pylori (Up) positive duodenal ulcer. METHODS: 118 patients with lip positive duodenal ulcer admitted into Yuzhou City Central Hospital from Jan. 2015 to Feb. 2016 were selected and divided into observation group and control group via the random number table, with 59 cases in each group. The control group was treated with quadruple therapy of omeprazole, amoxicillin, clarithromycin and bismuth potassium citrate, while the observation group was given quadruple therapy of rabeprazole sodium, amoxicillin, clarithromycin and bismuth potassium citrate, both groups received a two-week continuous treatment. The clinical efficacy and lip eradication were observed, and the incidence of adverse ding reactions of two groups was compared. RESULTS: After treatment, the total effective rate of the observation group (91. 53% , 54/59) was significantly higher than that of the control group (76.27% , 45/59) ; the rate of lip eradication of observation group (96.61% , 57/59) was significantly higher than that of the control group (81.36%, 48/59), with statistically significant difference (P <0.05); there was no statistical significance in incidence of adverse drug reactions between two groups (P > 0.05). CONCLUSIONS: The efficacy of quadruple therapy of rabeprazole sodium, amoxicillin, clarithromycin and bismuth potassium citrate in treatment of lip positive duodenal ulcer is remarkable, with effective Hp eradication, less adverse drug reactions and high safety. [ABSTRACT FROM AUTHOR]

Two selective stability-indicating HPLC methods are described for determination of rabeprazole sodium (RZ)-mosapride citrate (MR) and RZ-itopride hydrochloride (IO) mixtures in the presence of their ICH-stress formed degradation products. Separations were achieved on X-Bridge C18 column using two mobile phases: the first for RZ-MR mixture consisted of acetonitrile: 0.025 M KH2PO4 solution: TEA (30:69:1 v/v; pH 7.0); the second for RZ-IO mixture was at ratio of 25:74:1 (v/v; pH 9.25). The detection wavelength was 283 nm. The two methods were validated and validation acceptance criteria were met in all cases. Peak purity testing using contrast angle theory, relative absorbance and log A versus the wavelengths plots were presented. The % recoveries of the intact drugs were between 99.1% and 102.2% with RSD% values less than 1.6%. Application of the proposed HPLC methods indicated that the methods could be adopted to follow the stability of their formulations. [ABSTRACT FROM AUTHOR]

Statistical experimental design was used to optimize the chromatographic separations of two pharmaceutical compounds from their respective potential impurities. A fractional factorial design was utilized to study the effects of pH, organic solvent in mobile phases A&B, and flow rate on the resolution of Rabeprazole and Rabeprazole Sulfone, which had closely eluting peaks. A desirability function applied to the optimized conditions predicted the peak resolution between 2.2 and 2.7 for the Rabeprazole & Rabeprazole Sulfone impurity. The chromatographic method employed an Acquity UPLC, BEH C18 column (100 × 2.1 mm i.d., 1.7 μm particle size) with the mobile phase consisting of a phosphate buffer, pH 6.5, and acetonitrile in a gradient program. The flow rate and injection volumes were 0.45 mL/min & 5 μl, respectively, and detection was done at 254 nm. The chromatographic method was validated for linearity, accuracy, precision, specificity, and ruggedness according to ICH guidelines. The results clearly showed that the quality by design concept could be effectively applied to optimize a UPLC chromatographic method with fewer trials and error-free experimentation. [ABSTRACT FROM AUTHOR]

Two simple, accurate, precise, economical procedures, entailing neither irksome sample treatment nor tedious extraction process have been developed for the simultaneous estimation of rabeprazole sodium and levosulpiride in combined tablet dosage form. The first method was based on employing simultaneous equation method for analysis of both drugs. Rabeprazole sodium and levosulpiride have shown absorbance maxima at 284 and 232 nm in methanol, respectively. The second method was based on derivative spectrophotometric method involving the determination of both the drugs at their respective zero crossing point (ZCP). The first order derivative spectrum was obtained in methanol and the determinations were made at 231.2 nm (ZCP of levosulpiride) for rabeprazole sodium and 246.2 nm (ZCP of rabeprazole sodium) for levosulpiride. The linearity was obeyed in the concentration range of 1-20 μg/ml for both drugs. The medium of dissolution was used 900 ml of phosphate buffer pH 7.4 using a USP type 2 apparatus at a stirring rate of 100 rpm. The drug release was evaluated by developed spectroscopic methods. The suitability of the developed method for quantitative determination of rabeprazole sodium and levosulpiride was proved by validation. [ABSTRACT FROM AUTHOR]