Oxybutynin Chloride Extended-Release Tablets
» Oxybutynin Chloride Extended-Release Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of oxybutynin chloride (C22H31NO3·HCl).
Packaging and storage—
Preserve in tight containers. 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: Infrared Absorption 
197
—
197—
Test specimen—
Add a quantity of finely powdered Tablets, equivalent to about 15 mg of oxybutynin chloride, to 5 mL of water per Tablet. Mix for 1 minute. Adjust with 0.1 N sodium hydroxide to a pH between 7 and 8. Extract the solution twice with 10 mL of ether. Combine the extracts, evaporate the ether, and dry under vacuum over silica gel for at least 30 minutes. Redissolve the dried residue in a small amount of acetone, transfer the solution to an IR salt plate, and evaporate to cast a thin film.
Standard specimen—
Dissolve 15 mg of USP Oxybutynin Chloride RS in 5 mL of water. Proceed as directed for the Test specimen, beginning with “Adjust with”.
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—
711—
test 1—
Medium:
simulated gastric fluid without enzymes; 50 mL.
Apparatus 7:
Drug Release 724, 30 cycles per minute; 2- to 3-cm amplitude.
724, 30 cycles per minute; 2- to 3-cm amplitude.
Times:
4, 10, and 24 hours.
Determine the amount of C22H31NO3·HCl dissolved by employing the following method.
0.035 M Phosphate buffer, pH 2.2—
Dissolve about 4.83 g of monobasic sodium phosphate in 1000 mL of water, add 2.3 mL of triethylamine, and adjust with phosphoric acid to a pH of 2.2 ± 0.2.
Acidified water—
To 1 L of water add phosphoric acid dropwise to a pH of 3.5, and mix well.
Standard stock solutions—
Dissolve accurately weighed quantities of USP Oxybutynin RS in acetonitrile, and dilute quantitatively, and stepwise if necessary, with acetonitrile to obtain solutions having known concentrations of about 250, 300, and 350 µg per mL.
Standard solutions—
Prepare a series of dilutions of the Standard stock solutions in acidified water having final concentrations similar to those expected in the Test solution.
Test solution—
Use portions of the solution under test. If the solution is cloudy, centrifuge at 2000 rpm for 10 minutes, and use the supernatant.
Mobile phase—
Prepare a suitable filtered and degassed mixture of 0.035 M Phosphate buffer, pH 2.2 and acetonitrile (65:35). Make adjustments if necessary (see System Suitability under Chromatography 621).
621).
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 230-nm detector and a 4.6-mm × 5-cm column that contains packing L11. The flow rate is about 1.5 mL per minute. The column temperature is maintained at about 35
. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the tailing factor is greater than 0.5 and less than 2.5; and the relative standard deviation for replicate injections is not more than 2.0%.
621)—
The liquid chromatograph is equipped with a 230-nm detector and a 4.6-mm × 5-cm column that contains packing L11. The flow rate is about 1.5 mL per minute. The column temperature is maintained at about 35. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the tailing factor is greater than 0.5 and less than 2.5; 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 solutions and the Test solution into the chromatograph, record the chromatograms, and measure the peak responses. Construct a calibration curve by plotting the peak response versus concentration of the Standard solutions. A weighing factor, 1/x, is applied to the regression line of the calibration curve to enhance the accuracy of the low standard concentrations. Determine the amount of C22H31NO3·HCl dissolved in each interval from a linear regression analysis of the calibration curve.
Tolerances—
The percentages of the labeled amount of C22H31NO3·HCl dissolved at the times specified conform to Acceptance Table 2.
for tablets labeled to contain 5 mg or 10 mg of oxybutynin chloride:
| Time (hours) |  Amount dissolved |
| 4 | not more than 20% |
| 10 | between 34.5% and 59.5% |
| 24 | not less than 80% |
for tablets labeled to contain 15 mg of oxybutynin chloride:
| Time (hours) | Amount dissolved |
| 4 | not more than 20% |
| 10 | between 34.5% and 59.5% |
| 24 | not less than 75% |
test 2—
If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 2.
Medium—
acid stage:
simulated gastric fluid, without enzymes, pH 1.2 ± 0.05; 250 mL (first row).
buffer stage:
simulated intestinal fluid, without enzymes, pH 6.8 ± 0.1; 250 mL (rows 2 to 4).
Apparatus 3:
25 dips per minute; 20-mesh polypropylene screen on top and bottom; 30 seconds drip time.
Times:
2 hours in the Acid stage (first row); 4, 8, and 16 hours in the Buffer stage (rows 2 to 4).
Determine the amount of C22H31NO3·HCl dissolved by employing the following method.
Buffer solution—
Transfer 1 mL of triethylamine to 1000 mL of water. Adjust with phosphoric acid to a pH of 3.50 ± 0.05.
Mobile phase—
Prepare a filtered and degassed mixture of acetonitrile and Buffer solution (4:1). Make adjustments if necessary (see System Suitability under Chromatography 621).
621).
Standard stock solution—
Transfer 20 mg, accurately weighed, of USP Oxybutynin Chloride RS to a 100-mL volumetric flask, dissolve in and dilute with Acid stage Medium to volume, and mix.
Working standard solution—
Transfer 5.0 mL of the Standard stock solution, for Tablets labeled to contain 5 mg, or 10 mL, for Tablets labeled to contain 10 mg, to a 100-mL volumetric flask; dilute with Buffer stage Medium to volume; and mix.
Test solution—
Centrifuge a portion of the solution under test at approximately 3000 rpm for 10 minutes. Use the supernatant.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 203-nm detector and a 4.6-mm × 25-cm column that contains packing L7. The flow rate is about 1.5 mL per minute. Chromatograph the Working 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 3.0%.
621)—
The liquid chromatograph is equipped with a 203-nm detector and a 4.6-mm × 25-cm column that contains packing L7. The flow rate is about 1.5 mL per minute. Chromatograph the Working 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 3.0%.
Procedure—
Separately inject equal volumes (about 25 µL) of the Working standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the amount of C22H31NO3·HCl dissolved by the following formulas:
Percentage dissolved at each time point (Ct):
in which rU and rS are the peak responses for the Test solution and the Working standard solution, respectively; CS is the concentration, in mg per mL, of the Working standard solution; 250 is the volume, in mL, of Medium; 100 is the conversion factor to percentage; and LC is the Tablet label claim, in mg.
Percentage dissolved at 4 hours:
C2 + C4
Percentage dissolved at 8 hours:
C2 + C4 + C8
Percentage dissolved at 16 hours:
C2 + C4 + C8 + C16
Tolerances—
The percentages of the labeled amount of C22H31NO3·HCl dissolved at the times specified conform to Acceptance Table 2.
| Time (hours) | Amount dissolved |
| 2 | between 0% and 10% |
| 4 | between 10% and 30% |
| 8 | between 40% and 65% |
| 16 | not less than 80% |
Uniformity of dosage units 905:
meet the requirements.
905:
meet the requirements.
Related compounds—
Mobile phase, Diluent, Preparation medium, Impurity stock solution, System suitability solution, and Chromatographic system—
Proceed as directed in the Assay.
Impurity standard solution—
Dilute the Impurity stock solution with Diluent to obtain a solution having a known concentration of about 1 µg of oxybutynin related compound A per mL. [note—Oxybutynin related compound A is phenylcyclohexylglycolic acid.]
Test solution—
Use the Assay preparation.
Procedure—
Separately inject equal volumes (about 50 µL) of the Impurity standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the percentage of each impurity in the portion of Tablets taken by the formula:
C(rU / rS)
in which C is the concentration, in µg per mL, of oxybutynin related compound A in the Impurity standard solution; and rU and rS are the peak responses for each impurity obtained from the Test solution and the Impurity standard solution, respectively. Disregard any peak less than 0.1%: not more than 1% of oxybutynin related compound A is found, and not more than 2% of total impurities is found.
Assay—
Mobile phase—
Prepare a mixture of water, acetonitrile, and triethylamine (65:35:0.15). Adjust with phosphoric acid to a pH of 3.9, degas, and filter.
Diluent—
Use water adjusted with phosphoric acid to a pH of 3.5.
Preparation medium—
Prepare a solution of methanol and acetonitrile (1:1).
Impurity stock solution—
Dissolve an accurately weighed quantity of USP Oxybutynin Related Compound A RS in acetonitrile to obtain a solution having a known concentration of about 0.11 mg per mL.
Standard stock preparation—
Dissolve an accurately weighed quantity of USP Oxybutynin Chloride RS in acetonitrile to obtain a solution having a known concentration of about 0.37 mg per mL.
System suitability solution—
Transfer 10 mL of the Standard stock preparation and 1 mL of the Impurity stock solution into a 100-mL volumetric flask, dilute with Diluent to volume, and mix.
Standard preparation—
Dilute the Standard stock preparation with Diluent to obtain a solution having a known concentration of about 0.1 mg per mL.
Assay preparation—
for tablets that contain 5 mg of oxybutynin chloride—
Place 10 Tablets in a 500-mL volumetric flask, add 150 mL of Preparation medium, and stir for at least 4 hours or until dissolved. Dilute with Diluent to volume. Mix thoroughly, centrifuge, and use the clear supernatant.
for tablets that contain 10 mg of oxybutynin chloride or more—
Place 10 Tablets in a 1000-mL volumetric flask, add 300 mL of Preparation medium, and stir for at least 4 hours or until dissolved. Dilute with Diluent to volume. If necessary, make a further dilution with Diluent to obtain a solution having a final concentration equivalent to 0.1 mg per mL of oxybutynin chloride. Mix thoroughly, centrifuge, and use the clear supernatant.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 220-nm detector and a 4.6-mm × 15-cm column that contains packing L11. The flow rate is about 1.5 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are about 1.0 for oxybutynin and about 1.6 for oxybutynin related compound A; the resolution, R, between oxybutynin and oxybutynin related compound A is not less than 1.5; the tailing factor is greater than 0.75 and not more than 2.5 for each peak; and the relative standard deviation of peak area responses for six replicate injections is not more than 3% for each compound.
621)—
The liquid chromatograph is equipped with a 220-nm detector and a 4.6-mm × 15-cm column that contains packing L11. The flow rate is about 1.5 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are about 1.0 for oxybutynin and about 1.6 for oxybutynin related compound A; the resolution, R, between oxybutynin and oxybutynin related compound A is not less than 1.5; the tailing factor is greater than 0.75 and not more than 2.5 for each peak; and the relative standard deviation of peak area responses for six replicate injections is not more than 3% for each compound.
Procedure—
Separately inject equal volumes (about 50 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the area responses for the major peaks. Calculate the quantity, in mg, of oxybutynin chloride (C22H31NO3·HCl) in the portion of Tablets taken by the formula:
CVD(rU / rS)
in which C is the concentration, in mg per mL, of oxybutynin chloride in the Standard preparation; V is the volume, in mL, of the Assay preparation; D is the dilution factor; and rU and rS are the peak area 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—
| Topic/Question | Contact | Expert Committee |
| Monograph | Elena Gonikberg, Ph.D.
Senior Scientist 1-301-816-8251 |
(MDGRE05) Monograph Development-Gastrointestinal Renal and Endocrine |
| Reference Standards | Lili Wang, Technical Services Scientist 1-301-816-8129 RSTech@usp.org |
|
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientist 1-301-816-8106 |
(BPC05) Biopharmaceutics05 |
USP32–NF27 Page 3163
Pharmacopeial Forum: Volume No. 33(4) Page 671
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.