Drug release 
724
—
Medium:
water; 900 mL, 1800 mL for 400-mg Tablets.
Apparatus 1:
100 rpm.
Times:
3, 6, 12, and 24 hours.
Procedure—
Determine the amount of C
15H
12N
2O dissolved by employing UV absorption at the wavelength of maximum absorbance at about 284 nm on filtered portions of the solution under test, suitably diluted with
Medium, if necessary, in comparison with a Standard solution having a known concentration of
USP Carbamazepine RS in the same
Medium.
Tolerances—
The percentages
(Q) of the labeled amount of C
15H
12N
2O dissolved at the times specified conform to
Acceptance Table 1.
| Time (hours) |
Amount dissolved |
| 3 |
between 10% and 35% |
| 6 |
between 35% and 65% |
| 12 |
between 65% and 90% |
| 24 |
not less than 75% |
Dissolution 711—
Medium:
water; 900 mL, 1800 mL for 400-mg Tablets.
Apparatus 1:
100 rpm.
Times:
3, 6, 12, and 24 hours.
Procedure—
Determine the amount of C
15H
12N
2O dissolved by employing UV absorption at the wavelength of maximum absorbance at about 284 nm on filtered portions of the solution under test, suitably diluted with
Medium, if necessary, in comparison with a Standard solution having a known concentration of
USP Carbamazepine RS in the same
Medium.
Tolerances—
The percentages
(Q) of the labeled amount of C
15H
12N
2O dissolved at the times specified conform to
Acceptance Table 2.
| Time (hours) |
 Amount dissolved |
| 3 |
between 10% and 35% |
| 6 |
between 35% and 65% |
| 12 |
between 65% and 90% |
| 24 |
not less than 75% |
(Official April 1, 2006)
Uniformity of dosage units 905:
meet the requirements.
PROCEDURE FOR CONTENT UNIFORMITY—
Standard stock solution—
Dissolve an accurately weighed quantity of USP Carbamazepine RS in methanol to obtain a solution containing 2 mg per mL.
Standard solution—
Quantitatively dilute an accurately measured volume of Standard stock solution with methanol to obtain a solution having a known concentration of 10 µg per mL.
Test solution—
Finely powder 1 Tablet, and quantitatively transfer the powder, with the aid of methanol, to a 100-mL volumetric flask. Add about 70 mL of methanol, and shake by mechanical means for 60 minutes. Sonicate for 15 minutes, and dilute with methanol to volume. Allow to stand for 10 to 15 minutes. Dilute a portion of the clear solution quantitatively, and stepwise if necessary, with methanol to obtain a solution containing about 10 µg of carbamazepine per mL.
Procedure—
Concomitantly determine the absorbances of the
Test solution and the
Standard solution by employing UV absorption at the wavelength of maximum absorbance at about 284 nm, using methanol as a blank. Calculate the quantity, in mg, of carbamazepine (C
15H
12N
2O) in the Tablet taken by the formula:
(LC / D)(AU / AS),
in which
L is the labeled quantity, in mg, of carbamazepine in the Tablet;
C is the concentration, in µg per mL, of
USP Carbamazepine RS in the
Standard solution; D is the concentration, in µg per mL, of the
Test solution, based on the labeled quantity per Tablet and the extent of dilution; and
AU and
AS are the absorbances obtained from the
Test solution and the
Standard solution, respectively.
Limit of residual solvents—
Standard solution—
Dissolve accurately measured quantities of methanol and methylene chloride in dimethylformamide to obtain a solution having known concentrations of about 5 µg of each per mL.
Test solution—
Finely powder 10 Tablets, and quantitatively transfer the powder to a 50-mL volumetric flask. Add about 30 mL of dimethylformamide, shake by mechanical means for 60 minutes, and sonicate for 2 minutes. Dilute with dimethylformamide to volume, and mix. Centrifuge a portion of the solution at about 2500 rpm for 20 minutes, and use the clear supernatant.
Chromatographic system (see Chromatography 621)—
The gas chromatograph is equipped with a flame-ionization detector and a 2-mm × 3-m glass column containing 0.2% phase G39 on support S7. The injection port and detector temperatures are maintained at about 170
and 300
, respectively. The column temperature is programmed as follows. Initially it is maintained at 75
for 10 minutes, then increased at a rate of 20
per minute to 155
, and maintained at 155
for 30 minutes. The carrier gas is helium, flowing at a rate of about 10 mL per minute.
Procedure—
Separately inject equal volumes (about 2 µL) of the
Test solution and the
Standard solution into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the amount, in µg, of methylene chloride and methanol in each Tablet taken by the formula:
5C(rU / rS),
in which
C is the concentration, in µg per mL, of methylene chloride or methanol in the
Standard solution; and
rU and
rS are the responses of the corresponding analyte obtained from the
Test solution and the
Standard solution, respectively: not more than 23 µg of methylene chloride per Tablet is found; and not more than 100 µg of methanol per Tablet is found.
Chromatographic purity—
Not more than 0.2% of any individual impurity is found; and not more than 0.5% of total impurities is found, the results from both
Test 1 and
Test 2 being used.
TEST 1—
Mobile phase and Chromatographic system—
Prepare as directed in the Assay.
System suitability solution—
Dissolve suitable quantities of phenytoin and
USP Carbamazepine RS in methanol to obtain a solution containing about 0.6 and 0.2 mg per mL, respectively. Dilute this solution quantitatively, and stepwise if necessary, with methanol to obtain a solution containing about 60 µg of phenytoin and 20 µg of
USP Carbamazepine RS per mL.
Standard solution—
Dissolve an accurately weighed quantity of
USP Carbamazepine RS in methanol, and dilute quantitatively, and stepwise if necessary, with methanol to obtain a solution having a known concentration of about 4 µg per mL.
Test solution—
Use the Assay stock preparation.
Procedure—
Separately inject equal volumes (about 10 µL) of the
Test solution and the
Standard 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:
100(CS / CT)(ri / rS),
in which
CS is the concentration, in mg per mL, of
USP Carbamazepine RS in the
Standard solution; CT is the concentration, in mg per mL, of carbamazepine in the
Test solution; ri is the peak response of each impurity obtained from the
Test solution; and
rS is the peak response for carbamazepine obtained from the
Standard solution.
TEST 2—
Mobile phase—
Prepare a filtered and degassed mixture of water, methanol, and acetonitrile (10:7:3). Make adjustments if necessary (see
System Suitability under
Chromatography 621).
System suitability solution—
Dissolve suitable quantities of iminostilbene and
USP Carbamazepine RS in methanol to obtain a solution containing about 12.5 and 5.0 µg per mL, respectively.
Standard solution—
Use the Standard solution, prepared as directed for Test 1.
Test solution—
Use the Assay stock preparation.
Chromatographic system (see Chromatography 621)—
Prepare as directed in the
Assay. Chromatograph the
System suitability solution, and record the peak responses as directed for
Procedure: the relative retention times are about 0.3 for carbamazepine and 1.0 for iminostilbene; the resolution,
R, between carbamazepine and iminostilbene is not less than 10.0; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure—
Proceed as directed for Test 1.
Assay—
Mobile phase—
Prepare a filtered and degassed mixture of water, methanol, and methylene chloride (600:450:45). Make adjustments if necessary (see
System Suitability under
Chromatography 621).
Internal standard solution—
Prepare a solution of phenytoin in methanol containing about 600 µg per mL.
Standard preparation—
Dissolve an accurately weighed quantity of
USP Carbamazepine RS in methanol, and dilute quantitatively, and stepwise if necessary, with methanol to obtain a solution having a known concentration of about 200 µg per mL. Pipet 10.0 mL of this solution into a conical flask, add 10.0 mL of
Internal standard solution, mix, and filter. This solution contains about 100 µg of
USP Carbamazepine RS per mL.
System suitability solution—
Pipet equal volumes of Internal standard solution and Standard preparation into a suitable flask, and mix.
Assay stock preparation—
Finely powder 10 Tablets, and quantitatively transfer the powder, with the aid of alcohol, to a volumetric flask of such volume that when the solution is diluted to volume a final concentration estimated to be about 4 mg of carbamazepine per mL is obtained. Shake by mechanical means for 60 minutes. Sonicate for 15 minutes, and dilute with methanol to volume. Allow to stand for 10 to 15 minutes, then filter a portion of the supernatant, and use the clear filtrate.
Assay preparation—
Transfer 5.0 mL of the Assay stock preparation to a 100-mL volumetric flask, dilute with methanol to volume, and mix. Pipet 10.0 mL of this solution into a conical flask, add 10.0 mL of Internal standard solution, mix, and filter.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 230-nm detector, a 4.6-mm × 30-mm guard column that contains 7-µm packing L7, and a 3.9-mm × 30-cm column that contains packing L1.
[NOTE—Wash the column with 50 to 100 mL of methanol before and after use.
] The flow rate is about 2 mL per minute. Chromatograph the
System suitability solution, and record the peak responses as directed for
Procedure: the relative retention times are about 0.8 for phenytoin, and 1.0 for carbamazepine; the resolution,
R, between phenytoin and carbamazepine is not less than 2.8; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 10 µL) of the
Standard preparation and the
Assay preparation into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the quantity, in mg, of carbamazepine (C
15H
12N
2O) in each Tablet taken by the formula:
0.004(CV)(RU / RS),
in which
C is the concentration, in µg per mL, of
USP Carbamazepine RS in the
Standard preparation; V is the volume, in mL, of the volumetric flask used to prepare the
Assay stock preparation; and
RU and
RS are the peak response ratios of carbamazepine to the internal standard obtained from the
Assay preparation and the
Standard preparation, respectively.
