Clarithromycin Extended-Release Tablets
» Clarithromycin Extended-Release Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of clarithromycin (C38H69NO13).
Packaging and storage
Preserve in well-closed containers, protected from light. Store at 25, excursions permitted between 15 and 30.
Labeling
When more than one Dissolution Test is given, the labeling states the Dissolution Test used only if Test 1 is not used.
Identification
The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
Dissolution 711
test 1
Medium:
0.3 M phosphate buffer, pH 6.0 (prepared by dissolving 816.5 g of monobasic potassium phosphate and 48 g of sodium hydroxide in about 4 L of water, mixing, and diluting with water to 20 L. Adjust with either concentrated phosphoric acid or 1 N sodium hydroxide to a pH of 6.0 ± 0.05); 900 mL.
Apparatus 2:
75 rpm.
Times:
30, 45, 60, and 120 minutes.
Determine the percentages of the labeled amount of clarithromycin (C38H69NO13) dissolved using the following method.
Standard solutions
Prepare five solutions of USP Clarithromycin RS dissolved in acetonitrile and diluted in Medium, with known concentrations over the range of about 60 to 600 µg per mL.
Test solution
Use portions of the solution under test passed through a 35-µm polyethylene filter.
Chromatographic system
Proceed as directed in the Assay.
Procedure
Separately inject equal volumes (about 50 µL) of the five Standard solutions and the Test solution into the chromatograph, and measure the responses for the major peaks. Perform a linear regression analysis to generate a standard curve using the peak area of each Standard solution versus its concentration. Determine the amount of clarithromycin (C38H69NO13) dissolved at each specified time interval, using the peak area of each Test solution and the linear regression statistics for the Standard solutions.
Tolerances
The percentages of the labeled amounts of clarithromycin (C38H69NO13) dissolved at the times specified conform to the following Acceptance Table.
Acceptance Table 1
test 2
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.
Medium:
0.05 M phosphate buffer, pH 6.8 containing 0.5% of sodium lauryl sulfate; 900 mL, degassed by sonication and vacuum.
Apparatus 1:
100 rpm.
Times:
2, 12, and 24 hours.
Determine the percentages of the labeled amount of clarithromycin (C38H69NO13) dissolved using the following method.
0.067 M Phosphate buffer, pH 2.5
Dissolve 9.2 g of monobasic sodium phosphate monohydrate in about 800 mL of water. Adjust with phosphoric acid to a pH of 2.5. Dilute with water to 1000 mL.
Mobile phase
Prepare a filtered and degassed mixture of methanol and 0.067 M Phosphate buffer, pH 2.5 (65:35). Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard solution
Transfer about 56 mg of USP Clarithromycin RS, accurately weighed, to a 100-mL volumetric flask. Add 10 mL of methanol, and sonicate to dissolve. Dilute with Medium to volume.
Test solution
Centrifuge the solution under test at 2500 rpm for 10 minutes.
Chromatographic system (see Chromatography 621)
The liquid chromatograph is equipped with a 210-nm detector and a 4.6-mm × 15-cm column that contains 5-µm packing L1. The flow rate is about 1.0 mL per minute. The column temperature is maintained at 50. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the tailing factor is not more than 2.0; the column efficiency is not less than 2000; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure
Separately inject equal volumes (about 5 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Determine the amount, in percentage, of clarithromycin dissolved by the formula:
in which CU is the concentration, in mg per mL, of clarithromycin in the sample at each time point; rU and rS are the peak responses obtained from the Test solution and the Standard solution, respectively; and CS is the concentration, in mg per mL, of clarithromycin in the Standard solution.
Calculate the amount, in percentage, of clarithromycin dissolved with volume correction:
in which Cn is the concentration, in mg per mL, of clarithromycin in the Test solution at each time point; 900 is the volume, in mL, of Medium; VU is the volume, in mL, of sample withdrawn at each time point; n is the number of time points [noteThe summation of the amount of clarithromycin removed at previous sampling time points is applicable only where n>1.]; 100 is the conversion factor to percentage; and LC is the Tablet label claim, in mg.
Tolerances
The percentages of the labeled amounts of clarithromycin (C38H69NO13) dissolved at the times specified conform to Acceptance Table 2.
test 3
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3.
Medium:
acetate buffer, pH 4.75 (prepared by dissolving 3.59 g of sodium acetate trihydrate and 11.0 mL of 2 N acetic acid in 1000 mL of water, and adjusting with 2 N acetic acid to a pH of 4.75); 1000 mL.
Apparatus 1:
10 mesh; 50 rpm.
Times:
1, 2, 4, 8, and 12 hours.
Determine the percentages of the labeled amount of clarithromycin (C38H69NO13) dissolved by employing the following method.
0.067 M Phosphate buffer
Dissolve 9.12 g of monobasic potassium phosphate in 1000 mL of water, and mix.
Mobile phase
Prepare a filtered and degassed mixture of methanol and 0.067 M Phosphate buffer (65:35), mix, and adjust with phosphoric acid to a pH of 4.0. Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard stock solution
Dissolve quantitatively an accurately weighed quantity of USP Clarithromycin RS in methanol, shaking and sonicating if necessary to ensure dissolution, to obtain a stock solution having a known concentration of about 625 µg of clarithromycin per mL, taking into account the stated potency, in µg per mg, of USP Clarithromycin RS.
Standard solution
Transfer 10.0 mL of the Standard stock solution to a 50-mL volumetric flask, dilute with Mobile phase to volume, and mix. This solution contains about 125 µg of clarithromycin per mL.
System suitability solution
Dissolve quantitatively an accurately weighed quantity of USP Clarithromycin Related Compound A RS in methanol to obtain a solution containing about 625 µg of clarithromycin related compound A per mL. Transfer 10 mL of this solution and 10 mL of the Standard stock solution to a 50-mL volumetric flask, dilute with Mobile phase to volume, and mix.
Test solution
Withdraw 10-mL of the solution under test. Transfer 3 mL to a 25-mL volumetric flask, and dilute with Mobile phase to volume. Pass portions of this dilution through a 0.45-µm filter. Replace 10 mL of Medium in each vessel.
Chromatographic system (see Chromatography 621)
The liquid chromatograph is equipped with a 210-nm detector and a 4.6-mm × 15-cm column that contains 5-µm packing L1. The flow rate is about 1.0 mL per minute. The column temperature is maintained at 50. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.75 for clarithromycin and 1.0 for clarithromycin related compound A; and the resolution, R, between clarithromycin and clarithromycin related compound A is not less than 2.0. Chromatograph the Standard solution, and record the responses as directed for Procedure: the column efficiency, determined from the clarithromycin peak, is not less than 750 theoretical plates; the tailing factor is not less than 0.9 and not more than 2; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure
Separately inject equal volumes (about 50 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Determine the amount, in percentage, of clarithromycin (C38H69NO13) dissolved by the formula:
in which CU is the concentration, in mg per mL, of clarithromycin in the sample at each time point; rU and rS are the peak responses obtained from the Test solution and the Standard solution, respectively; CS is the concentration, in mg per mL, of clarithromycin in the Standard solution; 100 is the conversion factor to percentage; and LC is the Tablet label claim, in mg.
Calculate the amount, in percentage, of clarithromycin dissolved with volume correction at time points n 2:
in which Cn is the concentration, in mg per mL, of clarithromycin in the Test solution at each time point; 900 is the volume, in mL, of Medium; VU is the volume, in mL, of sample withdrawn at each time point; n is the time point (at 2 hours, n = 2), summation of the concentration of the Test solution from the first to the (n 1)th time point (only applicable for n 2); 100 is the conversion factor to percentage; and LC is the Tablet label claim, in mg.
Tolerances
The percentages of the labeled amount of clarithromycin (C38H69NO13) dissolved at the times specified conform to Acceptance Table 2.
test 4
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 4.
Medium:
phosphate buffer, pH 6.0 (prepared by dissolving 68.0 g of potassium dihydrogen phosphate and 1.8 g of sodium hydroxide in 10 L of water, and adjusting with dilute sodium hydroxide or phosphoric acid to a pH of 6.0 ± 0.1); 900 mL.
Apparatus 2:
50 rpm.
Times:
2, 4, 8, and 12 hours.
Determine the percentages of the labeled amount of clarithromycin (C38H69NO13) dissolved by employing the following method.
Buffer solution
Dissolve 6.8 g of potassium dihydrogen phosphate in 1 L of water. Adjust with dilute sodium hydroxide or phosphoric acid to a pH of 4.5 ± 0.1.
Mobile phase
Prepare a filtered and degassed mixture of methanol and Buffer solution (64:36). Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard solution
Transfer about 20 mg of USP Clarithromycin RS, accurately weighed, to a 50-mL volumetric flask. Add about 30 mL of Medium, and sonicate until dissolved, about 10 minutes. Add 2 mL of methanol, and dilute with Medium to volume.
Test solution
Use the solution under test passed through a 0.45-µm suitable filter.
Chromatographic system (see Chromatography 621)
The liquid chromatograph is equipped with a 203-nm detector and a 4.0-mm × 12.5-cm column that contains 5-µm packing L7. The flow rate is about 1.0 mL per minute. The column temperature is maintained at 30. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the tailing factor is not more than 2.0, 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 solution and the Test solution into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Determine the amount, in percentage, of clarithromycin dissolved by the formula:
in which CU is the concentration, in mg per mL, of clarithromycin in the Test solution at each time point; rU and rS are the peak responses obtained from the Test solution and the Standard solution, respectively; and CS is the concentration, in mg per mL, of clarithromycin in the Standard solution.
Calculate the amount, in percentage, of clarithromycin dissolved at each time point by the formula:
in which Cn is the concentration, in mg per mL, of clarithromycin in the Test solution at each time point; 900 is the volume, in mL, of Medium; VS is the volume, in mL, of the sample taken at each time point; and LC is the Tablet label claim, in mg.
Tolerances
The percentages of the labeled amount of clarithromycin (C38H69NO13) dissolved at the times specified conform to Acceptance Table 2.
Loss on drying 731
Dry a portion of powdered Tablets in vacuum at a pressure not exceeding 5 mm of mercury at 110 for 3 hours: it loses not more than 5.0% of its weight.
Uniformity of dosage units 905:
meet the requirements.
Assay
Mobile phase, Resolution solution, and Chromatographic system
Proceed as directed in the Assay under Clarithromycin Tablets.
Standard preparation
Prepare as directed for Standard preparation in the Assay under Clarithromycin Tablets.
Assay preparation
Finely powder an accurately counted number of Tablets, equivalent to about 2000 mg of clarithromycin. With the aid of methanol quantitatively transfer the powder to a 500-mL volumetric flask, add about 350 mL of methanol, and shake by mechanical means for 30 minutes. Dilute with methanol to volume, and mix. Sonicate for 30 minutes. Cool to room temperature, and allow to stand for at least 16 hours. Mix, and allow any insoluble matter to settle. Transfer 3.0 mL of the supernatant to a 100-mL volumetric flask, dilute with Mobile phase to volume, and mix. Pass a portion of this solution through a filter having a 0.5-µm or finer porosity, and use the filtrate as the Assay preparation.
Procedure
Proceed as directed for Procedure in the Assay under Clarithromycin Tablets. Calculate the quantity, in mg, of clarithromycin (C38H69NO13) in each Extended-Release Tablet taken by the formula:
(50/3)(C/N)(rU / rS)
in which N is the number of Tablets taken, and the other terms are as defined therein.
Auxiliary Information
Please check for your question in the FAQs before contacting USP.
Chromatographic Column
USP32NF27 Page 1959
Pharmacopeial Forum: Volume No. 32(3) Page 775
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.
|