Omeprazole solution

Add propylene glycol and poloxamer to a clean vessel (main mix). 

While stirring, heat the mixture as appropriate to sufficiently melt the poloxamer. 

Once a uniform solution is obtained, remove from heat source and continue mixing. 

In a separate vessel (alcohol premix) add alcohol, omeprazole base, and monoammonium glycerizzinate and mix until uniform. In another vessel (water premix), add water, EDTA, 

Add the alcohol containing premix to the main mixing vessel containing the poloxamer. 

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Cao and Zeng [52] used of an oscillopolarographic method for the determination and the electrochemical behavior of omeprazole. Portions of standard omeprazole solution were treated with 1 ml 1 M ammonia/ ammonium chloride at pH 8.9 and the solution was diluted with water to 10 ml. The diluted solution was subjected to single sweep oscillopolaro-graphy with measurement of the derivative reduction peak at —1.105 V versus saturated calomel electrode. The calibration graph was linear from 0.5 to 10 /iM omeprazole with a detection limit of 0.2 fiM. The method was applied to the analysis of omeprazole in capsules with recoveries of 100-118.6% and RSD of 6.78%. The electrochemical behavior of omeprazole at the mercury electrode was also investigated. 

Mathew, M., et al. Stability of omeprazole solutions at various pH values as determined by high-performance liquid chromatography. Drug. Dev. Ind. Pharm. 1995, 21, 965-971. 

Omeprazole Very slightly soluble in water, soluble in alcohol, methanol, and methylene chloride. It dissolves in dilute solution of alkali hydroxides [3]. 

Claramunt et al. [22] used a H and 13C NMR to study the tautomer-isim of omeprazole in solution. The tautomeric equilibrium constant, KT = 0.59 in tetrahydrofuran at 195 K, is in favor of the 6-methoxy tautomer. The assignment of the signals was made by comparison with its two N-methyl derivatives in acetone-d6 and through theoretical calculations of the absolute shieldings (GIAO/DFT/6-3111++G ). 

Test C Examine the chromatograms obtained in the test for omeprazole impurity C. The principal spot in the chromatogram obtained with test solution (b) is similar in position and size to the principal spot in the chromatogram obtained with reference solution (a). Place the plate in a tank saturated with vapor of acetic acid R. The spots rapidly turn brown. 

Solution S Dissolve 0.5 g of omeprazole in methylene chloride R and dilute to 25 ml with the same solvent. 

Absorbance When this test is carried out according to the general procedure (2.2.25), the absorbance of solution S measured at 440 nm is not more than 0.1 (this limit corresponds to 0.035% of omeprazole impurity F or omeprazole impurity G). 

Test solution (a). Dissolve 0.1 g of omeprazole in 2 ml of a mixture of equal volumes of methanol R and methylene chloride R. 

Apply to the plate 10 pi of each solution. Develop over a path of 15 cm using a mixture of 20 volumes of 2-propanol R, 40 volumes of methylene chloride R previously shaken with concentrated ammonia R (shake 100 ml of methylene chloride R with 30 ml of concentrated ammonia R in a separating funnel allow the layers to separate and use the lower layer) and 40 volumes of methylene chloride R. Allow the plates to dry in air. Examine in UV light at 254 nm. Any spot in the chromatogram obtained with test solution (a) with a higher R value than that of the spot due to omeprazole is not more intense than the spot in the chromatogram obtained with reference solution (b) (0.1%). 

Reference solution (a). Dissolve 1 mg of omeprazole CRS and 1 mg of omeprazole impurity D CRS in the mobile phase and dilute to 10 ml with the mobile phase. 

Test C Ignite 1 g of omeprazole and cool. Add 1 ml of water R to the residue and neutralize with hydrochloric acid R. Filter and dilute the filtrate to 4 ml with water R. 0.1 ml of the solution gives reaction (b) of sodium, this test should be carried according to the general procedure (2.3.1). 

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 A The Rf value of the principal spot observed in the chromatogram of the Identification solution corresponds to that of the principal spot observed in the chromatogram of the Standard solution containing 0.15 mg of USP Omeprazole RS per ml, obtained as directed in the test for Chromatographic purity, Method 1. 

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]. 

Procedure Inject equal volumes (about 40 p ) of the Test solution and Diluent into the chromatograph, and allow the Test solution to elute for not less than two times the retention time of omeprazole. Record the chromatograms, and measure the peak responses. Calculate the percentage of each impurity in the portion of omeprazole taken by the formula ... 

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 p ) of the Standard solution and Test solution into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of omeprazole (Ci7H19N303S) dissolved in the medium by the formula ... 

Standard solution 1 (for Capsules labeled 10 mg) Dissolve an accurately weighed quantity of USP Omeprazole RS in alcohol to obtain a solution having a known concentration of about 2 mg/ml. Dilute with pH 6.8 Phosphate buffer quantitatively, and stepwise if necessary, to obtain a solution having a known concentration of about 0.01 mg/ml. Immediately add 2 ml of 0.25 M sodium hydroxide to 10 ml of this solution, and mix. [Note Do not allow the solution to stand before adding the sodium hydroxide solution.]... 

Procedure Proceed as directed for Acid resistance stage with a new set of capsules from the same batch. After 2 h, replace the acid Medium with the buffer Medium and continue the test for 45 more minutes. Determine the amount of C17H19N3O3S dissolved from UV absorbances at the wavelength of maximum absorbance at about 305 nm on portions of the solutions under test passed through 0.2-p.m nylon filter, in comparison with a Standard solution having a known concentration of USP Omeprazole RS and the same Medium. 

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]. 

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