Orphenadrine Citrate Extended-Release Tablets
» Orphenadrine Citrate Extended-Release Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of orphenadrine citrate (C18H23NO·C6H8O7).
Packaging and storage—
Preserve in well-closed, 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.
USP Reference standards 
11
—
11—
USP Orphenadrine Citrate RS 
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USP Orphenadrine Related Compound B RS
N-Ethyl-N,N-dimethyl [2-2(methylbenzhydryloxy)ethyl]ammonium chloride.
C20H28ClNO 333.90
N-Ethyl-N,N-dimethyl [2-2(methylbenzhydryloxy)ethyl]ammonium chloride.
C20H28ClNO 333.90
USP Orphenadrine Related Compound C RS
N-Methyl [2-(2-methylbenzhydryloxy)ethyl]amine hydrochloride.
C17H22ClNO 291.82
N-Methyl [2-(2-methylbenzhydryloxy)ethyl]amine hydrochloride.
C17H22ClNO 291.82
Identification—
A:
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:
water; 900 mL, deaerated.
Apparatus 2:
50 rpm.
Times:
1, 2, 6, and 12 hours.
Determine the amount of C18H23NO·C6H8O7 dissolved by employing the following procedure.
0.05 M Ammonium phosphate—
Transfer 5.75 g of monobasic ammonium phosphate to a 1000-mL volumetric flask, dissolve in and dilute with water to volume, and mix well.
Mobile phase—
Prepare a filtered and degassed mixture of 0.05 M Ammonium phosphate and acetonitrile (3:2), and adjust with phosphoric acid to a pH of 3.2 ± 0.1. Make adjustments if necessary (see System Suitability under Chromatography 621).
621).
Standard solution—
Transfer about 25 mg, accurately weighed, of USP Orphenadrine Citrate RS to a 25-mL volumetric flask. Add about 10 mL of Mobile phase, and sonicate until dissolved. Dilute with Mobile phase to volume, and mix. Transfer 5.0 mL of this solution to a 50-mL volumetric flask, dilute with Medium to volume, and mix.
Test solution—
Pass a portion of the solution under test through a suitable filter having a porosity of 0.45 µm, and discard the first few mL of the filtrate.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 225-nm detector and a 3.9-mm × 30-cm column that contains packing L1. The flow rate is about 2.0 mL per minute. 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%.
621)—
The liquid chromatograph is equipped with a 225-nm detector and a 3.9-mm × 30-cm column that contains packing L1. The flow rate is about 2.0 mL per minute. 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 peak responses. Calculate the quantity of C18H23NO·C6H8O7 dissolved by the following formulas.
The percentage dissolved after 1 hour is determined by the formula:
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The percentage dissolved after 2 hours is determined by the formula:
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where
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The percentage dissolved after 6 hours is determined by the formula:
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where
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The percentage dissolved after 12 hours is determined by the formula:
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where
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In the formulas above, rU and rS are the peak responses for the Test solution and the Standard solution, respectively; CS is the concentration, in mg per mL, of the Standard solution; 900 is the volume, in mL, of Medium; 100 is the conversion factor to percentage; LC is the Tablet label claim, in mg; V1 is the volume, in mL, of sample withdrawn at the first hour; V2 is the volume, in mL, of the sample withdrawn at the second hour; and V3 is the volume, in mL, of the sample withdrawn at the sixth hour.
Tolerances—
The percentages of the labeled amount of C18H23NO·C6H8O7 dissolved at the times specified conform to Acceptance Table 2.
| Time (hours) |  Amount dissolved |
|---|---|
| 1 | between 10% and 40% |
| 2 | between 30% and 50% |
| 6 | between 50% and 80% |
| 12 | not less than 80% |
test 2—If the product complies with this test, the labeling indicates that the product meets USP Dissolution Test 2.
Medium:
water; 900 mL.
Apparatus 2:
50 rpm.
Times:
1, 4, and 12 hours.
Determine the amount of C18H23NO·C6H8O7 dissolved by employing the following procedure.
Standard solution—
Transfer about 50 mg, accurately weighed, of USP Orphenadrine Citrate RS to a 50-mL volumetric flask, and dissolve in and dilute with Medium to volume. Transfer 1.0 mL of this solution to a 50-mL volumetric flask, and dilute with Medium to volume.
Test solution—
Withdraw 10 mL of the solution under test from each vessel at each specified time point. Replace 10 mL of Medium in each vessel. Pass the solution under test through a suitable filter having a porosity of 0.45 µm. Transfer 1.0 mL of the filtrate to a 50-mL volumetric flask, and dilute with Medium to volume.
Procedure—
Determine the amount of C18H23NO·C6H8O7 dissolved by UV absorption at the wavelength of maximum absorbance at about 210 nm on portions of the Test solution in comparison with the Standard solution, using a cell with a path length of 1 cm and using Medium as the blank. Calculate the percentage of C18H23NO·C6H8O7 dissolved at each time point.
Tolerances—
The percentages of the labeled amount of orphenadrine citrate dissolved at the times specified conform to Acceptance Table 2.
| Time (hours) | Amount dissolved |
|---|---|
| 1 | between 10% and 40% |
| 4 | between 40% and 70% |
| 12 | not less than 80% |
Uniformity of dosage units 905:
meet the requirements.
905:
meet the requirements.
Related compounds—
Buffer solution and Mobile phase—
Proceed as directed for the Assay.
System suitability solution—
Dissolve accurately weighed quantities of USP Orphenadrine Citrate RS, USP Orphenadrine Related Compound B RS, and USP Orphenadrine Related Compound C RS in Mobile phase to obtain a solution having a known concentration of about 0.1 mg per mL of USP Orphenadrine Citrate RS and about 0.01 mg per mL each of USP Orphenadrine Related Compound B RS and USP Orphenadrine Related Compound C RS.
Test solution—
Use the Assay preparation.
Chromatographic system—
Prepare as directed for the Assay. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the resolution, R, between orphenadrine citrate and orphenadrine related compound C is not less than 1.2; and that between orphenadrine citrate and orphenadrine related compound B is not less than 2.0. Identify the peaks using the approximate relative retention times shown in the table.
| Peak Identification | Relative Retention Time (RRT) |
Relative Response Factor (F) |
Limit (%) |
|---|---|---|---|
| Citric acid | 0.4 | — | — |
| Orphenadrine related compound C1 | 0.9 | 1.5 | NMT 0.5 |
| Orphenadrine citrate | 1 | — | — |
| Orphenadrine related compound B2 | 1.3 | 1.3 | NMT 0.5 |
| 2-Methyl benzhydrol | 2.1 | 2.1 | NMT 0.5 |
| 2-Methyl benzophenone | 4 | 1.0 | NMT 0.5 |
| Any other individual impurity | — | 1.0 | NMT 0.10 |
| Total of all related compounds | — | — | NMT 1.5 |
|
1
N-Methyl [2-(2-methylbenzhydryloxy)ethyl]amine hydrochloride.
2
N-Ethyl-N,N-dimethyl[2-2(methylbenzhydryloxy)ethyl]ammonium chloride.
|
|||
Procedure—
Inject a volume (about 20 µL) of the Test solution into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the percentage of each of the (known or unknown) individual orphenadrine citrate related compounds in the portion of Tablets taken by the formula:
(100/F) (rU / rS)
in which F is the appropriate relative response factor as listed in the table; rU is the individual peak response of each of the related compounds in the Test solution; and rS is the peak response of the orphenadrine citrate in the Test solution.
Assay—
Buffer solution—
Dissolve 5.75 g of monobasic ammonium phosphate in 1000 mL of water, and adjust with phosphoric acid to a pH of 3.2 ± 0.1.
Mobile phase—
Prepare a filtered and degassed mixture of Buffer solution and acetonitrile (6:4). Make adjustments if necessary (see System Suitability under Chromatography 621).
621).
Standard preparation—
Dissolve an accurately weighed quantity of USP Orphenadrine Citrate RS in Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having a known concentration of about 0.1 mg per mL.
Assay preparation—
Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 100 mg of orphenadrine citrate, to a 200-mL volumetric flask; add 100 mL of Mobile phase; sonicate for about 5 minutes; and shake mechanically for 15 minutes. Dilute with Mobile phase to volume, and mix. Pass a portion of this solution through a suitable filter of type PVDF having a porosity of 0.45 µm or finer. Transfer about 10 mL of the filtrate to a 50-mL volumetric flask, dilute with Mobile phase to volume, and mix.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 225-nm detector and a 3.9-mm × 30-cm column that contains packing L1. The flow rate is about 2.0 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the tailing factor for orphenadrine citrate is not more than 2.0; and the relative standard deviation for replicate injections is not more than 2.0%.
621)—
The liquid chromatograph is equipped with a 225-nm detector and a 3.9-mm × 30-cm column that contains packing L1. The flow rate is about 2.0 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the tailing factor for orphenadrine citrate 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 major peaks. Calculate the percentage, based on the label claim, of orphenadrine citrate (C18H23NO·C6H8O7) in the portion of Tablets taken by the formula:
100(CS / CU) (rU / rS)
in which CS is the concentration, in mg per mL, of USP Orphenadrine Citrate RS in the Standard preparation; CU is the concentration, in mg per mL, of orphenadrine citrate, based on the label claim, in 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.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Hariram Ramanathan, M.S.
Associate Scientific Liaison 1-301-816-8313 |
(SM42010) Monographs - Small Molecules 4 |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
|
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
USP35–NF30 Page 4136
Pharmacopeial Forum: Volume No. 34(3) Page 643