Dissolution 
711
—
Test 1:
Medium:
water; 900 mL.
Apparatus 1:
50 rpm.
Times:
30, 60, and 120 minutes.
Determine the amount of C15H11N2NaO2 dissolved by employing the following method.
Mobile phase—
Prepare a filtered and degassed mixture of methanol and water (7:3). Make adjustments if necessary (see
System Suitability under
Chromatography 621).
Standard solution—
Prepare a solution of
USP Phenytoin RS in methanol, and dilute with water to obtain a solution having a concentration similar to that of the solution under test.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 229-nm detector and a 4.6-mm × 25-cm column that contains packing L1. The flow rate is about 1 mL per minute. Chromatograph the
Standard solution, and record the peak responses as directed for
Procedure: the column efficiency is not less than 3200 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 10 µL) of the
Standard solution and the solution under test into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of phenytoin sodium (C
15H
11N
2NaO
2) dissolved by the formula:
(274.25/252.27)900C(rU /rS),
in which 274.25 and 252.27 are the molecular weights of phenytoin sodium and phenytoin, respectively;
C is the concentration, in mg per mL, of
USP Phenytoin RS in the
Standard solution; and
rU and
rS are the peak responses obtained from the solution under test and the
Standard solution, respectively.
Tolerances (for products labeled as 30-mg capsules)—
The percentage of the labeled amount of C
15H
11N
2NaO
2 dissolved is not more than 40%
(Q) in 30 minutes, is 56% (
Q¢) in 60 minutes, and is not less than 65% (
Q¢¢) in 120 minutes. The requirements are met if the quantities dissolved from the Capsules tested conform to the accompanying
Acceptance Table.
Acceptance Table
| Stage |
Number Tested |
Acceptance Criteria |
| S1 |
6 |
Each unit is within the range between Q  15% and Q 5%, is within the range Q¢ ± 10%, and is not less than Q ¢¢ + 5% at the stated Times. |
| S2 |
6 |
Average of 12 units (S1 + S2) is within the range between Q 10% and Q, is within the range Q¢ ± 8%, and is not less than Q¢¢; no unit is outside the range between Q 20% and Q + 10%, no unit is outside the range Q¢ ± 18%, and no unit is less than Q¢¢ 10% at the stated Times. |
| S3 |
12 |
Average of 24 units (S1 + S2 + S3) is within the range between Q 10% and Q, is within the range Q¢ ± 8% and is not less than Q¢¢; not more than 2 units are outside the range between Q 20% and Q + 10%, and no unit is outside the range Q 30% and Q + 20%; not more than 2 units are outside the range Q¢ ± 18%, and no unit is outside the range Q¢ ± 25%; not more than 2 units are less than Q¢¢ 10%, and no unit is less than Q¢¢ 20% at the stated Times. |
Tolerances (for products labeled as 100-mg capsules)—
The percentage of the labeled amount of C
15H
11N
2NaO
2 dissolved is not more than 45%
(Q) in 30 minutes, is 60% (
Q¢) in 60 minutes, and is not less than 70% (
Q¢¢) in 120 minutes. The requirements are met if the quantities dissolved from the Capsules tested conform to the accompanying
Acceptance Table.
Acceptance Table
| Stage |
Number Tested |
Acceptance Criteria |
| S1 |
6 |
Each unit is within the range between Q 25% and Q 5%, is equal to Q¢ ± 20%, and is not less than Q ¢¢ + 5% at the stated Times. |
| S2 |
6 |
Average of 12 units (S1 + S2) is within the range between Q 20% and Q, is within the range Q¢ ± 15%, and is not less than Q¢¢; no unit is outside the range between Q 30% and Q + 10%, no unit is outside the range Q¢ ± 25%, and no unit is less than Q¢¢ 10% at the stated Times. |
| S3 |
12 |
Average of 24 units (S1 + S2 + S3) is within the range between Q 20% and Q, is within the range Q¢ ± 15% and is not less than Q¢¢; not more than 2 units are outside the range between Q 30% and Q + 10%, and no unit is outside the range between Q 40% and Q + 20%; not more than 2 units are outside the range Q¢ ± 25%, and no unit is outside the range Q¢ ± 35%; not more than 2 units are less than Q¢¢ 10%, and no unit is less than Q¢¢ 20% at the stated Times. |
Test 2:
If the product complies with this test, the labeling indicates that it meets USP
Dissolution Test 2. Proceed as directed in
Test 1, except for using
Apparatus 1 at 75 rpm and the following
Tolerances.
Tolerances (for products labeled as 100-mg capsules)—
The percentage of the labeled amount of C
15H
11N
2NaO
2 dissolved is not more than 45%
(Q) in 30 minutes, is 65% (
Q¢) in 60 minutes, and is not less than 70% (
Q¢¢) in 120 minutes. The requirements are met if the quantities dissolved from the Capsules tested conform to the accompanying
Acceptance Table.
Test 3:
If the product complies with this test, the labeling indicates that it meets USP
Dissolution Test 3.
Medium:
water; 900 mL.
Apparatus 1:
75 rpm.
Times:
30, 60, and 120 minutes.
Determine the amount of C15H11N2NaO2 dissolved by employing the method described under Test 1.
Tolerances (for products labeled as 200-mg and 300-mg capsules)—
The percentage of the labeled amount of C
15H
11N
2NaO
2 dissolved is not more than 30%
(Q) in 30 minutes, is 50% (
Q¢) in 60 minutes, and is not less than 60% (
Q¢¢) in 120 minutes. The requirements are met if the quantities dissolved from the Capsules tested conform to the accompanying
Acceptance Table.
Related compounds—
Phosphate buffer and Mobile phase—
Proceed as directed in the Assay.
Standard solution—
Dissolve accurately weighed quantities of
USP Phenytoin RS, USP Phenytoin Related Compound A RS, and
USP Phenytoin Related Compound B RS in methanol, and dilute quantitatively, and stepwise if necessary, with methanol to obtain a solution having known concentrations of about 600, 3, and 3 µg per mL, respectively.
Test solution—
Use the Assay preparation.
Chromatographic system (see Chromatography 621)—
Prepare as directed in the
Assay. Chromatograph the
Standard solution, and record the peak responses as directed for
Procedure: the relative retention times are about 0.38 for phenytoin related compound A, 0.45 for phenytoin related compound B, and 1.0 for phenytoin; the resolution,
R, between phenytoin related compound B and phenytoin is not less than 8, and the resolution,
R, between phenytoin related compound A and phenytoin related compound B is not less than 1.5; the tailing factor for the phenytoin peak is not more than 2.0; and the relative standard deviation for replicate injections is not more than 2.0% determined from phenytoin, and not more than 5.0% determined from phenytoin related compound A or phenytoin related compound B.
Procedure—
Separately inject equal volumes (about 10 µL) of the
Standard solution and the
Test solution into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in µg, of each phenytoin related compound in the portion of Capsules taken by the formula:
100C(rU / rS),
in which
C is the concentration, in µg per mL, of the appropriate USP Reference Standard in the
Standard solution; and
rU and
rS are the peak responses for the corresponding phenytoin related compound obtained from the
Test solution and the
Standard solution, respectively: not more than 0.5% of phenytoin related compound A is found; and not more than 1.0% of phenytoin related compound B is found.
Assay—
Phosphate buffer—
Prepare a solution of 0.05 M monobasic potassium phosphate in water, adjust with phosphoric acid to a pH of 3.5, and mix.
Mobile phase—
Prepare a filtered and degassed mixture of methanol and
Phosphate buffer (11:9). Make adjustments if necessary (see
System Suitability under
Chromatography 621).
Standard preparation—
Dissolve an accurately weighed quantity of
USP Phenytoin RS in methanol, and dilute quantitatively, and stepwise if necessary, with
Mobile phase to obtain a solution having a known concentration of about 0.6 mg per mL.
Assay preparation—
Transfer the contents of 10 Capsules to a 250-mL volumetric flask. Add about 150 mL of methanol, and sonicate for 20 minutes. Cool to room temperature, dilute with methanol to volume, mix, and filter. Transfer an accurately measured portion of the filtered solution, equivalent to about 60 mg of phenytoin, to a 100-mL volumetric flask, dilute with Mobile phase to volume, and mix.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 229-nm detector and a 4.6-mm × 25-cm column that contains packing L1. The flow rate is about 1 mL per minute. Chromatograph the
Standard preparation, and record the peak responses as directed for
Procedure: the column efficiency is not less than 3000 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 10 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 quantity, in mg, of phenytoin sodium (C
15H
11N
2NaO
2) in the portion of Capsules taken by the formula:
(274.25/252.27)100C(rU / rS),
in which 274.25 and 252.27 are the molecular weights of phenytoin sodium and phenytoin, respectively;
C is the concentration, in mg per mL, of
USP Phenytoin RS in the
Standard preparation; and
rU and
rS are the peak responses obtained from the
Assay preparation and the
Standard preparation, respectively.
for 30 minutes. Sonicate for 60 minutes with occasional shaking. Dilute with methanol to volume, and mix. Dilute with Mobile phase, if necessary, to obtain a final concentration of about 0.5 mg per mL.