Oxycodone Hydrochloride Extended-Release Tablets
» Oxycodone Hydrochloride Extended-Release Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of oxycodone hydrochloride (C18H21NO4·HCl).
Packaging and storage
Preserve in tight, light-resistant containers, and store at controlled room temperature.
Labeling
When more than one Dissolution Test is given, the labeling states the Dissolution Test used only if Test 1 is not used.
Identification
A: Thin-Layer Chromatographic Identification Test 201
Test solution
Transfer a portion of powdered Tablets, equivalent to about 5 mg of oxycodone hydrochloride, to a suitable screw-capped tube, add 5 mL of chloroform, sonicate for about 30 seconds, shake for several minutes, and centrifuge. Use the clear supernatant.
Standard solution:
0.9 mg of USP Oxycodone RS per mL of chloroform.
Application volume:
20 µL.
Developing solvent solution:
a mixture of acetone, toluene, ether, and ammonium hydroxide (6:4:1:0.3).
Procedure
Proceed as directed in the chapter. Spray with iodoplatinate TS: the RF value, color, and size of the principal spot obtained from the Test solution correspond to those obtained from the Standard solution; and no other spot is observed.
B:
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:
simulated gastric fluid (without enzymes); 900 mL.
Apparatus 1:
100 rpm.
Times:
1, 2, 4, 6, and 8 hours, for Tablets labeled to contain 10 mg, 20 mg, or 40 mg; 1, 2, 4, and 6 hours, for Tablets labeled to contain 80 mg.
Determine the amount of oxycodone (C18H21NO4) dissolved by employing the following method.
Standard stock solution
For Tablets labeled to contain 10 mg, transfer about 39.8 mg of USP Oxycodone RS, accurately weighed, into a 100-mL volumetric flask, and dissolve in and dilute with Medium to volume. For Tablets labeled to contain 20 mg, 40 mg, or 80 mg, transfer about 39.8 mg of USP Oxycodone RS, accurately weighed, into a 50-mL volumetric flask, and dissolve in and dilute with Medium to volume.
Working standard solution
Dilute the Standard stock solution with Medium to obtain solutions containing L/900 mg per mL, with L being the oxycodone Tablet label claim, in mg.
Procedure
Determine the amount of oxycodone (C18H21NO4) dissolved from UV absorption at a wavelength of about 226 nm (shoulder), using filtered portions of the solution under test, suitably diluted with Medium, if necessary, in comparison with the appropriate Working standard solution. Use Medium as the blank, and a 1.0-cm cell for Tablets labeled to contain 10 mg, 20 mg, or 40 mg; and a 0.5-cm cell for Tablets labeled to contain 80 mg. For Tablets labeled to contain 10 mg, 20 mg, or 40 mg, calculate the amount of oxycodone (C18H21NO4) dissolved by formula (1),
in which C is the concentration, in mg per mL, of the appropriate Working standard solution; AU and AS are the absorbances of the solution under test and of the appropriate Working standard solution, respectively; V is the initial volume, in mL, of Medium in the vessel; VS is the volume, in mL, withdrawn from the vessel for previous samplings; C1 is the concentration, in mg per mL, of oxycodone in the Medium determined at 1 hour; C2 is the concentration, in mg per mL, of oxycodone in the Medium determined at 2 hours; C4 is the concentration, in mg per mL, of oxycodone in the Medium determined at 4 hours; C6 is the concentration, in mg per mL, of oxycodone in the Medium determined at 6 hours; C8 is the concentration, in mg per mL, of oxycodone in the Medium determined at 8 hours; 100 is the conversion factor to percentage; and L is the Tablet label claim, in mg.
For Tablets labeled to contain 80 mg, calculate the amount of oxycodone (C18H21NO4) dissolved by formula (2),
in which C is the concentration, in mg per mL, of the appropriate Working standard solution; AU and AS are the absorbances of the solution under test and of the appropriate Working standard solution, respectively; V is the initial volume, in mL, of Medium in the vessel; VS is the volume, in mL, withdrawn from the vessel for previous samplings; C1 is the concentration, in mg per mL, of oxycodone in the Medium determined at 1 hour; C2 is the concentration, in mg per mL, of oxycodone in the Medium determined at 2 hours; C4 is the concentration, in mg per mL, of oxycodone in the Medium determined at 4 hours; C6 is the concentration, in mg per mL, of oxycodone in the Medium determined at 6 hours; 100 is the conversion factor to percentage; and L is the Tablet label claim, in mg.
Tolerances
The percentages of the labeled amount of oxycodone (C18H21NO4) dissolved at the times specified conform to Acceptance Table 2.
for tablets labeled to contain 10 mg, 20 mg, or 40 mg:
for tablets labeled to contain 80 mg:
test 2
If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 2.
Medium:
simulated gastric fluid (without enzymes); 900 mL.
Apparatus 1:
100 rpm.
Times:
1, 4, and 12 hours.
Determine the amount of oxycodone (C18H21NO4) dissolved by employing the following method.
0.85% Phosphoric acid
Dilute 10 mL of phosphoric acid with water to 1 L.
Standard stock solution
Prepare a solution of USP Oxycodone RS in 0.85% Phosphoric acid containing about 0.9 mg per mL.
Working standard solution
Dilute the Standard stock solution, quantitatively and stepwise, with Medium to obtain a solution having a concentration of about 40% of the Tablet label claim. [noteThis solution is stable for two weeks at room temperature.]
Test solution
Pass the solution under test through a suitable 0.45-µm filter.
Mobile phase
Weigh 23.1 g of monobasic potassium phosphate into a 4-L flask, and dissolve with 3400 mL of water. Add 4 mL of triethylamine, and adjust with 0.85% Phosphoric acid to a pH of 3.0 ± 0.1. Add 600 mL of methanol and 20 mL of tert-butyl methyl ether, and mix well. Filter and degas. Make adjustments if necessary (see System Suitability under Chromatography 621).
Chromatographic system (see Chromatography 621)
The liquid chromatograph is equipped with a 230-nm detector and a 3.9-mm × 30-cm column that contains 10-µm packing L1 and that is maintained at a temperature of 60. The flow rate is about 1.0 mL per minute. Chromatograph the Working standard solution, and record the peak responses as directed for Procedure: the tailing factor is not more than 1.5 and not less than 0.75; the capacity factor is not less than 0.5; and the relative standard deviation for replicate injections is not more than 2%.
Procedure
Separately inject equal volumes (about 50 µL) of the Working standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the peak reponses. Calculate the amount of oxycodone (C18H21NO4) dissolved by formula (3),
in which C is the concentration, in mg per mL, of the appropriate Working standard solution; rU and rS are the peak responses of the solution under test and of the appropriate Working standard solution, respectively; V is the initial volume, in mL, of Medium in the vessel under test; VS is the volume, in mL, withdrawn from the vessel for previous samplings; C1 is the concentration, in mg per mL, of oxycodone in the Medium determined at 1 hour; C4 is the concentration, in mg per mL, of oxycodone in the Medium determined at 4 hours; C12 is the concentration, in mg per mL, of oxycodone in the Medium determined at 12 hours; 100 is the conversion factor to percentage; and L is the Tablet label claim, in mg.
Tolerances
The percentages of the labeled amount of oxycodone (C18H21NO4) dissolved at the times specified conform to Acceptance Table 2.
for tablets labeled to contain 10 mg:
for tablets labeled to contain 20 mg:
for tablets labeled to contain 40 mg:
for tablets labeled to contain 80 mg:
Uniformity of dosage units 905:
meet the requirements.
Assay
Buffer solution
Dissolve 1.5 g of sodium heptanesulfonate in 740 mL of water. Mix with 10 mL of glacial acetic acid, adjust with 5 N sodium hydroxide solution to a pH of 3.50 ± 0.05, and mix.
Mobile phase
Prepare a filtered and degassed mixture of Buffer solution and acetonitrile (75:25). Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation
Dissolve an accurately weighed quantity of USP Oxycodone RS in Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having a known concentration of about 0.036 mg per mL.
Assay stock preparation
Transfer 10 Tablets into an appropriate volumetric flask, add a volume of a mixture of methanol and acetonitrile (50:50) equivalent to 50% of the volumetric flask volume, sonicate for about 10 minutes, and stir for about 20 minutes. Dilute with Buffer solution to volume, and mix.
Assay preparation
Transfer a volume of the Assay stock preparation, equivalent to 4 mg of oxycodone hydrochloride, into a 100-mL volumetric flask, dilute with Mobile phase to volume, and mix. Pass a portion of the solution through a suitable filter, and use the filtrate.
Chromatographic system (see Chromatography 621)
The liquid chromatograph is equipped with a 280-nm detector and a 4.6-mm × 15-cm column that contains packing L1. The flow rate is about 1.0 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the column efficiency is not less than 4000 theoretical plates; 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 preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the oxycodone peak. Calculate the quantity, in mg, of oxycodone hydrochloride (C18H21NO4·HCl) in the portion of Tablets taken by the formula:
(351.82/315.37)CD(rU / rS)
in which 351.82 and 315.37 are the molecular weights of oxycodone hydrochloride and oxycodone base, respectively; C is the concentration, in mg per mL, of USP Oxycodone RS in the Standard preparation; D is the dilution factor, in mL, for the Assay preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information
Please check for your question in the FAQs before contacting USP.
Chromatographic Column
USP32NF27 Page 3167
Pharmacopeial Forum: Volume No. 32(6) Page 1745
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.
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