Mesalamine Delayed-Release Tablets
» Mesalamine Delayed-Release Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of mesalamine (C7H7NO3).
Packaging and storage— Preserve in tight containers.
USP Reference standards 11
USP Mesalamine RS Click to View Structure
USP Salicylic Acid RS Click to View Structure
Identification, Infrared Absorption 197K
Test specimen— To about 50 mL of water add a quantity of finely powdered Tablets, equivalent to about 800 mg of mesalamine. Boil the mixture for about 5 minutes, with constant stirring. Filter the hot solution, and allow the filtrate to cool. Collect the precipitated crystals, and dry at about 110.
Dissolution 711
pH 6.0 Phosphate buffer— Transfer about 43.35 g of monobasic potassium phosphate and 1.65 g of sodium hydroxide to a 2-L volumetric flask. Dissolve in and dilute with water to volume, and mix. Adjust with 1 N sodium hydroxide or phosphoric acid to a pH of 6.0, and mix.
Sodium hydroxide solution— Transfer 133.6 g of sodium hydroxide to a 2-L volumetric flask, dissolve in and dilute with water to volume, and mix.
Media: 0.1 N hydrochloric acid, 500 mL for Acid stage; pH 6.0 Phosphate buffer, 900 mL for Buffer stages.
Apparatus 2: 100 rpm for Acid stage and for Buffer stage 1; 50 rpm for Buffer stage 2.
Times: 2 hours for Acid stage; 1 hour for Buffer stage 1; 90 minutes for Buffer stage 2.
acid stage— After 2 hours of operation, withdraw an aliquot of the fluid, discard the remaining solution, and retain the Tablets in proper order, so that each will be returned to its respective vessel later on. Blot the Tablets with a paper towel to dry, and proceed immediately as directed for Buffer stage 1.
Procedure— Determine the amount of C7H7NO3 dissolved by employing UV absorption at the wavelength of maximum absorbance at about 302 nm on filtered portions of the solution under test, suitably diluted with Medium, if necessary, in comparison with a Standard solution having a known concentration of USP Mesalamine RS, equivalent to about 1% of the labeled amount of C7H7NO3, in the same Medium.
Tolerances— The percentage of the labeled amount of C7H7NO3 dissolved from the units tested conforms to the Acceptance Table shown below. Continue testing through all levels unless the results conform at an earlier level.
buffer stage 1 [note—Use buffer that has been equilibrated to a temperature of 37 ± 0.5. ] Transfer pH 6.0 Phosphate buffer to each of the dissolution vessels, and place each Tablet from the Acid stage into its respective vessel. After 1 hour remove a 50-mL aliquot, and proceed immediately as directed for Buffer stage 2.
Procedure— Determine the amount of C7H7NO3 dissolved by employing UV absorption at the wavelength of maximum absorbance at about 330 nm on filtered portions of the solution under test, suitably diluted with Medium, if necessary, in comparison with a Standard solution having a known concentration of USP Mesalamine RS, equivalent to about 1% of the labeled amount of C7H7NO3, in the same Medium.
Tolerances— The percentage of the labeled amount of C7H7NO3 dissolved from the units tested conforms to the Acceptance Table shown below. Continue testing through all levels unless the results conform at an earlier level.
Acceptance Table
Level Number
Tested
Criteria
L1 6 No individual value exceeds 1% dissolved.
L2 6 Average of the 12 units (L1 + L2) is not more than 1% dissolved, and no individual unit is greater than 10% dissolved.
L3 12 Average of the 24 units (L1 + L2 + L3) is not more than 1% dissolved, and not more than one individual unit is greater than 10% dissolved.
buffer stage 2 Add 50 mL of Sodium hydroxide solution to each dissolution vessel to adjust to a pH of 7.2, and continue the run.
Procedure— Determine the amount of C7H7NO3 dissolved by employing UV absorption at the wavelength of maximum absorbance at about 332 nm on filtered portions of the solution under test, suitably diluted with Medium, if necessary, in comparison with a Standard solution having a known concentration of USP Mesalamine RS in the same Medium.
Tolerances— Not less than 80% (Q) of the labeled amount of C7H7NO3 is dissolved. The requirements are met if the quantities dissolved from the product conform to Acceptance Table 4. Continue testing through all levels unless the results conform at an earlier level.
Uniformity of dosage units 905: meet the requirements for Weight Variation.
Chromatographic purity—
Mobile phase— Proceed as directed in the Assay.
Chromatographic system— Proceed as directed in the Assay. To evaluate the system suitability requirements, use the System suitability preparation, Standard stock preparation, and the Standard preparation prepared as directed in the Assay.
Test solution— Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 400 mg of mesalamine, to a 500-mL volumetric flask. Add 50 mL of 1 N hydrochloric acid, and sonicate to dissolve. Shake by mechanical means for 10 minutes, dilute with water to volume, mix, and pass through a filter having a 0.5-µm or finer porosity. [note—Use an aliquot of this solution for the Assay preparation. ]
Procedure— Inject a volume (about 20 µL) of the Test solution into the chromatograph, record the chromatogram, and measure the areas for all the peaks. Calculate the percentage of each impurity in the portion of Tablets taken by the formula:
100(ri / rs)
in which ri is the peak response for each impurity; and rs is the sum of the responses of all the peaks: the largest secondary peak is not more than 1.0% of the total area; not more than 0.5% of any other individual impurity is found; and not more than 2.0% of total impurities is found.
Assay—
Mobile phase— Dissolve 4.3 g of sodium 1-octanesulfonate in 1 L of water. Adjust with phosphoric acid to a pH of 2.15, pass through a filter having a 0.45-µm or finer porosity, and degas.
System suitability preparation— Transfer about 20 mg each of 3-aminosalicylic acid and USP Salicylic Acid RS, accurately weighed, to a 200-mL volumetric flask. Dissolve in 50 mL of 1 N hydrochloric acid, sonicating to dissolve, dilute with water to volume, and mix. Dilute the solution so obtained quantitatively and stepwise with water, and mix to obtain a solution having known concentrations of about 0.01 mg each of 3-aminosalicylic acid and salicylic acid per mL.
Standard stock preparation— Transfer about 25 mg of USP Mesalamine RS, accurately weighed, to a 25-mL volumetric flask. Dissolve in 5 mL of 0.25 N hydrochloric acid, sonicating to dissolve, dilute with water to volume, and mix.
Standard preparation— Transfer 10.0 mL of Standard stock preparation and 5.0 mL of System suitability preparation to a 50-mL volumetric flask. Dilute with water to volume, mix, and pass through a filter having a 0.5-µm or finer porosity.
Assay preparation— Pipet a 25.0-mL aliquot of the Test solution, obtained as directed for the Chromatographic purity test, into a 100-mL volumetric flask, dilute with water to volume, mix, and pass through a filter having a 0.5-µm or finer porosity.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 230-nm detector, a 4.6-mm × 3.3-cm analytical column that contains 3-µm base-deactivated packing L1, and two 4.6-mm × 3.0-cm precolumns, each containing 10-µm packing L1 and being located between the pump and the injector. The flow rate is about 2 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the resolution, R, between mesalamine and salicylic acid or 3-aminosalicylic acid is not less than 2; the tailing factor is not more than 2; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— Separately inject equal volumes (about 20 µL) 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 mesalamine (C7H7NO3) in the portion of Tablets taken by the formula:
2000C(rU / rS)
in which C is the concentration, in mg per mL, of USP Mesalamine RS in the Standard preparation; and rU and rS are the mesalamine peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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