Omeprazole preparations

Other Formulations. Neural networks have been applied to the modeling of pellet formulations to control the release of theophylline [63] and to control the rate of degradation of omeprazole [64]. They have also been applied to the preparation of acrylic microspheres [65] and to model the release of insulin from an implant [66]. In arecent study from Brazil, the release of hydrocortisone from a biodegradable matrix has been successfully modeled [67]. 

Quercia RA, Fan Cr Liu X, etaf. Stability of omeprazole in an extemporaneously prepared oral liquid Am J Health SystPharm 1997 54 1833-1836 and Dunn A, White M, Reddy P, et al Delivery of omeprazole and lansoprazole granules through a nasogastric tube in vitro. Am J Health Syst Pharm 1999 56 2327-2330. 

Berzas Nevado, J. J., Castaneda Penalvo, G., and Rodriguez Dorado, R. M. (2005). Method development and validation for the separation and determination of omeprazole enantiomers in pharmaceutical preparations by capillary electrophoresis. Anal. Chim. Acta 533, 127-133. 

Losec MUPS is a proprietary preparation of omeprazole available as dispersible tablets that can be dispersed either in water or fruit juice. Tablets should not be chewed. 

Figure 3.6 Resolution of the enantiomers of omeprazole using a protein-derived CSP. The chromatogram shows the analysis of esomeprazole API artificially enriched with 0.1% w/w of the R-enantiomer. (Conditions cti-AGP 10 cm X 0.4 cm i.d. mobile phase sodium phosphate [pH 6.0, 60 mM] acetonitrile [85 15, v/v] flow rate 1 mbmin detection UV at 302 nm column temperature ambient sample preparation 0.02mg/ml in sodium phosphate [pH 11.0, 18 mM] methanol [98 2, v/v] injection volume 20 pi.)...

Preparation and administration of orai suspension - Take on an empty stomach 1 hour before a meal. The powder for oral suspension is supplied as unit-dose packets containing an immediate-release formulation of omeprazole. 

Gastrointestinal ulceration may occur less frequently than with some other NSAIDs. A preparation combining diclofenac and misoprostol decreases upper gastrointestinal ulceration but may result in diarrhea. Another combination of diclofenac and omeprazole was also effective with respect to the prevention of recurrent bleeding, but renal adverse effects were common in high-risk patients. Diclofenac, 150 mg/d, appears to impair renal blood flow and glomerular filtration rate. Elevation of serum aminotransferases occurs more commonly with this drug than with other NSAIDs. 

Brandstrom and Lamm [12] used the following method for the preparation of omeprazole ... 

Slemon and Macel [13] used several intermediates for the preparation of omeprazole. The drug was produced from the corresponding acetamide-sulfide compounds by a process of oxidation to form the amide sulfinyl compound, followed by alkaline hydrolysis to the sulfinyl carboxylate or salt, and decarboxylation. The methods are as follows ... 

Cotton etal. [14] described an asymmetric synthesis of esomeprazole. Esomeprazole, the (S)-enantiomer of omeprazole, was synthesized via asymmetric oxidation of prochiral sulfide 5-methoxy-2-[[(4-methoxy-3,5-dimethyl pyridin-2-yl)methyl]thio]-lH-benzimidazole 1. The asymmetric oxidation was achieved by titanium-mediated oxidation with cumene hydroperoxide in the presence of (S,S)-diethyl tartarate (DET). The enan-tioselectivity was provided by preparing the titanium complex in the presence of sulfide 1 at an elevated temperature and/or during a prolonged preparation time and by performing the oxidation of sulfide 1 in the presence of amine. An enantioselectivity of 94% ee was obtained using this method. 

Omeprazole was prepared [19] by reaction of 4-methoxy-o-phenyl-enediamine 1 with potassium ethyl xanthogenate 2 to give 5-methoxy-2-mercapto-lH-benzimidazole 3. Treatment of compound 3 with 3,5-dimethyl-4-methoxy-2-chloromethyl pyridine 4 in sodium hydroxide... 

Rao et al. [20] reviewed the synthetic method used to prepare omeprazole. The advantages and the disadvantages of the various methods are described. 

Heavy metals This test should be carried out as directed in the general procedure (2.4.8). One gram of omeprazole sodium complies with limit test C for heavy metals (20 ppm). Prepare the standard using 2 ml of lead standard solution (10 ppm Pb) R. 

Test B Infrared absorption—Carry out this test as directed in the general procedure (197 K). The IR absorption spectrum of a potassium bromide dispersion of omeprazole previously dried, exhibits maxima only at the same wavelength as that of similar preparation of USP Omeprazole RS. 

Solvents Prepare a mixture of dichloromethane and methanol (1 1). Standard solutions Dissolve an accurately weighed quantity of USP Omeprazole RS in Solvent, and mix to obtain Standard solution A having a known concentration of about 0.5 mg/ml. Dilute this solution quantitatively with Solvent to obtain Standard solution B and Standard solution C having known concentrations of about 0.15 and 0.05 mg/ml, respectively. 

Test solution Prepare a solution of Omeprazole in Solvent containing 50 mg/ml. 

Test solution Dissolve an accurately weighed quantity of omeprazole in Diluent to obtain a solution containing about 0.16 mg/ml [Note Prepare this solution fresh]. 

Assay preparation Transfer about 100 mg of Omeprazole, accurately weighed, to a 50-ml volumetric flask, dissolve in and dilute with Diluent to volume, and mix. Transfer 5 ml of this solution to a 50-ml volumetric flask, dilute with Diluent to volume, and mix. 

Procedure Separately inject equal volumes (about 20 pT) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of C17H19N3O3S in the portion of omeprazole taken by the formula ... 

Procedure After 2 h, remove each sample from the basket, and quantitatively transfer into separate volumetric flasks to obtain a solution having a final concentration of about 0.2 mg/ml. Proceed as directed for the Assay preparation in the Assay, starting with "Add about 50 ml of Diluent. Calculate the quantity, in mg, of omeprazole (C17H19N3O3S) dissolved in the Medium by the formula ... 

Assay preparation Weigh and mix the contents of not fewer than 20 Capsules. Transfer an accurately weighed portion of the mixture, equivalent to about 20 mg of omeprazole, to a 100-ml volumetric flask, add about 50 ml of Diluent, and sonicate for 15 min. Cool, dilute with Diluent to volume, mix, and pass through a membrane filter having 0.45 /im or finer porosity. [Note Bubbles may form just before bringing the solution to volume. Add a few drops of dehydrated alcohol to dissipate the bubbles if they persist for more than a few minutes]. 

Tuncel and Dogrukol-Ak [29] developed a flow-through spectropho-tometric method for the determination of omeprazole in pharmaceutical preparations containing enteric-coated pellets. Sample was dissolved in 100 ml 0.1 M sodium hydroxide and filtered. Portions were analyzed by flow-through spectrophotometry using a Spectrophoresis 100 system with 75 ym fused-silica capillaries with detection at 305 nm. Samples were pumped through the system for 2 min. Results were compared with those obtained by standard spectrophotometry at 305 nm. Detection limits was 8 fiM omeprazole and the calibration graph was linear. The pellet matrix did not interfere. RSD was 1.9% (n = 6). 

Wahbi et al. [32] used a spectrophotometric method for the determination of omeprazole in pharmaceutical formulations. The compensation method and other chemometric methods (derivative, orthogonal function, and difference spectrophotometry) have been applied to the direct determination of omeprazole in its pharmaceutical preparations. The method has been validated the limits of detection was 3.3 x 10 2 /ig/ml. The repeatability of the method was found to be 0.3-0.5%. The linearity range is 0.5-3.5 /ig/ml. The method has been applied to the determination of omeprazole in its gastro-resistant formulation. The difference spectrophotometric (AA) method is unaffected by the presence of acid induced degradation products, and can be used as a stability-indicating assay method. 

Dogrukol-Ak et al. [55] determined omeprazole in pharmaceutical preparations by a TLC densitometric method. Pellets from eneric coated capsules were finely powdered and dissolved in ethanolic 0.05 M potassium hydroxide with sonication. Four microliters of the solution was subjected to TLC on a silica gel FG254 plates with chloroform-methanol-25% ammonia (97.5 2.5 1) as mobile phase and densitometric detection of omeprazole (Rf = 0.46) at 302 nm. Calibration graphs were linear for 0.42—1.68 jug omeprazole the detection limit was 25 ng. In the determination of omeprazole in 20 mg Omeprazit, Omeprol, and Losec capsules, the found amounts were 20.2, 20.3, and 19.8 mg omeprazole, respectively, with corresponding RSD 1.9,1.8, and 1.6% (n = 8). The results agree with those of UV spectrophotometry. 

Zarghi et al. [76] developed an HPLC method, using a monolithic column, for quantification of omeprazole in plasma. The method is specific and sensitive with a quantification limit of 10 ng/ml. Sample preparation involves simple, one-step extraction procedure, and analytical recovery was complete. The separation was carried out in reversed-phase conditions using a Chromolith Performance (RP-18e, 100 x 4.6 mm) column with an isocratic mobile phase consisting of 0.01 mol/1 disodium hydrogen phosphate buffer-acetonitrile (73 27) adjusted to pH 7.1. The wavelength was set at 302 nm. The calibration curve was linear over the concentration range 20-1500 ng/ml. The coefficients of variation for intra- and interday assay were found to be less than 7%. 

El-Sherif et al. [79] developed and validated a reversed-phase HPLC method for the quantitative determination of omeprazole and two other proton pump inhibitors in the presence of their acid-induced degradation products. The drugs were monitored at 280 nm using Nova-Pak Ci8 column and mobile phase consisting of 0.05 M potassium dihydrogen phosphate-methanol-acetonitrile (5 3 2). Linearity range for omeprazole was 2-36 fig/ml. The recovery of omeprazole was 100.50 0.8%, and the minimum detection was 0.54 /zg/ml. The method was applied to the determination of pure, laboratory prepared mixtures, and pharmaceutical dosage forms. The results were compared with the official USP method for omeprazole. 

Berzas Nevado et al. [138] developed a new capillary zone electrophoresis method for the separation of omeprazole enantiomers. Methyl-/ -cyclodextrin was chosen as the chiral selector, and several parameters, such as cyclodextrin structure and concentration, buffer concentration, pH, and capillary temperature were investigated to optimize separation and run times. Analysis time, shorter than 8 min was found using a background electrolyte solution consisting of 40 mM phosphate buffer adjusted to pH 2.2, 30 mM /1-cyclodextrin and 5 mM sodium disulfide, hydrodynamic injection, and 15 kV separation voltage. Detection limits were evaluated on the basis of baseline noise and were established 0.31 mg/1 for the omeprazole enantiomers. The method was applied to pharmaceutical preparations with recoveries between 84% and 104% of the labeled contents. 

Zhao and Lou [164] studied the metabolism of omeprazole to its two major metabolites, hydroxyomeprazole and omeprazole sulfone, in rat liver microsomes by a reversed-phase HPLC assay. The formation of metabolites of omeprazole depended on incubation time, substrate concentration, microsomal protein concentration, and was found to be optimal at pH 7.4. The Pmax and Km of omeprazole hydroxylation in the rat liver microsomal preparation were 2033 nmol /(min mg protein), and 46.8 ymol/l, respectively. The effects of seven drugs on omeprazole metabolism were tested. Mephenytoin, five benzodiazepines and pava-verine caused inhibition of omeprazole metabolism. 

Quercia et al. [171] studied the stability of omeprazole 2 mg/ml in an extemporaneously prepared oral liquid. The contents of five 20-mg omeprazole capsules were mixed with 50 ml of 8.4% sodium bicarbonate solution in a Luer-Lok syringe. Three vials of this liquid were prepared for storage at 24,5, and — 20 °C. A 3-ml sample of each was taken initially and on days 1, 2, 3, 4, 6, 8, 10, 12, 14, 18, 22, 26, and 30 and assayed by HPLC. The liquids stored at 5 and — 20 °C did not change color during the study period, but the color of the liquid stored at 24 °C changed from white to brown. 

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