Methylphenidate Hydrochloride Extended-Release Tablets
» Methylphenidate Hydrochloride Extended-Release Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of methylphenidate hydrochloride (C14H19NO2·HCl).
Packaging and storage—
Preserve in tight containers.
Labeling—
When more than one Dissolution Test is given, the labeling states the Dissolution Test used only if Test 1 is not used.
Identification—
Place a portion of powdered Tablets, equivalent to about 100 mg of methylphenidate hydrochloride, in a 100-mL beaker. Add 20 mL of chloroform, stir for 5 minutes, and filter, collecting the filtrate. Evaporate the filtrate to about 5 mL. Add ethyl ether slowly, with stirring, until crystals form. Filter the crystals, wash with ethyl ether, and dry at 80
for 30 minutes: the IR absorption spectrum of a mineral oil dispersion of the crystals so obtained exhibits maxima only at the same wavelengths as that of a similar preparation of USP Methylphenidate Hydrochloride RS.
for 30 minutes: the IR absorption spectrum of a mineral oil dispersion of the crystals so obtained exhibits maxima only at the same wavelengths as that of a similar preparation of USP Methylphenidate Hydrochloride RS.
Dissolution 
711
—
711—
test 1—
Medium:
water; 500 mL.
Apparatus 2:
50 rpm.
Times:
1, 2, 3.5, 5, and 7 hours.
Test solution—
Use portions of the solution under test passed through a suitable 0.45-µm filter. [note—Do not use glass fiber filters.]
Procedure—
Determine the amount of C14H19NO2·HCl dissolved, employing the procedure set forth in the Assay, making any necessary volumetric adjustments.
Tolerances—
The percentages of the labeled amount of C14H19NO2·HCl dissolved at the times specified conform to Acceptance Table 2.
| Time (hours) |  Amount dissolved |
| 1 | between 25% and 45% |
| 2 | between 40% and 65% |
| 3.5 | between 55% and 80% |
| 5 | between 70% and 90% |
| 7 | not less than 80% |
test 2 (for products labeled for dosing every 24 hours)—
If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.
Medium:
acidified water (adjust with phosphoric acid to a pH of 3); 50 mL, at 37 ± 0.5.
.
Apparatus 7
(see Drug Release 724): 30 cycles per minute; 2–3 cm amplitude. Use Sample Preparation A using a metal coil sample holder (Figure 4d). Place 1 Tablet in the holder with the Tablet orifice facing down, and cover the top of the holder with Parafilm™. At the end of each specified test interval, the systems are transferred to the next row of new test tubes containing 50 mL of fresh Medium.
724): 30 cycles per minute; 2–3 cm amplitude. Use Sample Preparation A using a metal coil sample holder (Figure 4d). Place 1 Tablet in the holder with the Tablet orifice facing down, and cover the top of the holder with Parafilm™. At the end of each specified test interval, the systems are transferred to the next row of new test tubes containing 50 mL of fresh Medium.
Times:
1-hour intervals for a duration of 10 hours.
Determine the percentages of the labeled amount of C14H19NO2·HCl dissolved by employing the following method.
Dilution medium—
Prepare a mixture of Medium and acetonitrile (75:25).
Standard stock solution—
Dissolve an accurately weighed quantity of USP Methylphenidate Hydrochloride RS in Dilution medium to obtain a solution having a concentration of about 0.3 mg per mL.
Standard solution—
Prepare at least six solutions by making serial dilutions of the Standard stock solution in Dilution medium to bracket the expected drug concentration range.
Solution A—
Dissolve 2.0 g of 1-octanesulfonic acid sodium salt in 700 mL of water, mix well, and adjust with phosphoric acid to a pH of 3.0.
Mobile phase—
Prepare a filtered and degassed mixture of Solution A and acetonitrile (70:30). Make adjustments if necessary (see System Suitability under Chromatography 621).
621).
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 220-nm detector and a 3.2-mm × 5-cm column that contains 5-µm packing L1. The flow rate is about 1.0 mL per minute. The column temperature is maintained at 30. Chromatograph the Standard solution, and record the chromatogram as directed for Procedure: the tailing factor is not more than 2; the capacity factor is not less than 2; the relative standard deviation of the response is not more than 2%; and the relative standard deviation of the retention time is not more than 2%.
621)—
The liquid chromatograph is equipped with a 220-nm detector and a 3.2-mm × 5-cm column that contains 5-µm packing L1. The flow rate is about 1.0 mL per minute. The column temperature is maintained at 30. Chromatograph the Standard solution, and record the chromatogram as directed for Procedure: the tailing factor is not more than 2; the capacity factor is not less than 2; the relative standard deviation of the response is not more than 2%; and the relative standard deviation of the retention time is not more than 2%.
Procedure—
Separately inject equal volumes (about 25 µL) of the Standard solutions and the solution under test into the chromatograph. Record the chromatograms, and measure the peak responses. Construct a calibration curve by plotting the peak response versus the concentration of the Standard solutions. Determine the amount of C14H19NO2·HCl in each interval by linear regression analysis of the standard curve.
Tolerances—
The percentages of the labeled amount of C14H19NO2·HCl dissolved at the times specified conform to Acceptance Table 2.
Calculate the average percentage released from 3 to 6 hours using the formula:
in which Y is the cumulative drug released, in percentage, from 0 to 6 hours; and X is the cumulative drug released, in percentage, from 0 to 3 hours.
| Time (hours) | Amount dissolved |
| 1 | between 12% and 32% |
| 4 | between 40% and 60% |
| 10 | not less than 85% |
| average from 3 to 6 hours | between 9% and 15% per hour |
Uniformity of dosage units 905:
meet the requirements.
905:
meet the requirements.
Assay—
Proceed as directed in the Assay under Methylphenidate Hydrochloride Tablets, using Extended-Release Tablets.
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
Chromatographic Column—
| Topic/Question | Contact | Expert Committee |
| Monograph | Ravi Ravichandran, Ph.D.
Senior Scientist 1-301-816-8330 |
(MDPP05) Monograph Development-Psychiatrics and Psychoactives |
| 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 2950
Pharmacopeial Forum: Volume No. 33(4) Page 667
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.