Packaging and storage—
Preserve in tight, light-resistant containers.
Labeling—
Capsules that contain the macrocrystalline form of Nitrofurantoin are so labeled. When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.
Identification—
A:
Add 10 mL of 6 N acetic acid to a quantity of the contents of Capsules, equivalent to about 100 mg of nitrofurantoin, boil for a few minutes, and filter while hot. Cool to room temperature, collect the precipitate of nitrofurantoin, and dry at 105
for 1 hour: the IR absorption spectrum of a mineral oil dispersion of the precipitate so obtained exhibits maxima only at the same wavelength as that of a similar preparation of
USP Nitrofurantoin RS.
Dissolution 
711
—
TEST 1
(where it is labeled as containing Nitrofurantoin macrocrystals)—
Medium:
pH 7.2 (±0.05) phosphate buffer; 900 mL.
Apparatus 1:
100 rpm.
Times:
1, 3, and 8 hours.
Procedure—
Determine the amount of C
8H
6N
4O
5 dissolved by employing UV absorption at the wavelength of maximum absorbance at about 375 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 Nitrofurantoin RS in the same
Medium.
Tolerances—
The percentage of the labeled amount of C
8H
6N
4O
5 dissolved at the 1-hour point conforms to
Acceptance Table 1 under
Drug Release 724, and the percentages dissolved at the 3- and 8-hour points conform to the criteria for the final test time in
Acceptance Table 1 under
Drug Release 724.
| Time (hours) |
 Amount dissolved |
| 1 |
between 20% and 60% |
| 3 |
not less than 45% |
| 8 |
not less than 60% |
TEST 2
(where it is labeled as containing both Nitrofurantoin macrocrystalline and monohydrate forms)—If the product complies with this test, the labeling indicates that it meets USP
Dissolution Test 2.
Acid medium:
0.01 N hydrochloric acid for 1 hour; 900 mL.
pH 7.5 Buffer medium—
Prepare a pH 7.5 buffer concentrate by dissolving 62.2 g of potassium hydroxide and 129.3 g of monobasic potassium phosphate in water, dilute with water to 1 L, and mix. After 1 hour change the Acid medium to pH 7.5 Buffer medium by adding 50 mL of pH 7.5 buffer concentrate, for an additional 6 hours.
Apparatus 2:
100 rpm, with sinkers made of teflon-coated steel wire prepared by forming a coil approximately 22 mm long from a 13-cm length of 20-gauge wire (see
Figure 1).
Times:
1, 3, and 7 hours.
Acid-stage standard solution—
Prepare a solution of
USP Nitrofurantoin RS in
Acid medium to obtain a solution having a known concentration of about 0.025 mg per mL.
Buffer-stage standard solution—
Prepare a solution of
USP Nitrofurantoin RS in
pH 7.5 Buffer medium to obtain a solution having a known concentration of about 0.075 mg per mL.
Procedure—
Determine the amount of C8H6N4O5 dissolved from UV absorbances at the isosbestic wavelength at about 375 nm on filtered portions of each solution under test, suitably diluted, if necessary, with Acid medium or pH 7.5 Buffer medium when appropriate in comparison with the appropriate Standard solution.
Tolerances—
The percentages of the labeled amount of C
8H
6N
4O
5 dissolved at the specified times conform to the accompanying
Acceptance Table.
Time
(hours) |
Amount dissolved
(individual) |
Amount dissolved
(mean) |
| 1 |
between 2% and 16% |
between 5% and 13% |
| 3 |
between 27% and 69% |
between 39% and 56% |
| 7 |
not less than 68% |
not less than 81% |
Acceptance Table
| Level |
Number
Tested |
Criteria |
| L1 |
12 |
The mean percentage of dissolved label claim lies within the range for the means at each interval and is not less than the stated amount at the final test time. All individual values lie within the ranges for the individuals at each interval and are not less than the stated amount at the final test time. |
| L2 |
12 |
The mean percentage of dissolved label claim lies within the range for the means at each interval and is not less than the stated amount at the final test time. Not more than 2 of the 24 individual values lie outside the stated ranged for individuals at each interval, and not more than 2 of 24 are less than the stated amount at the final test time. |
Dissolution 711—
TEST 1
(where it is labeled as containing nitrofurantoin macrocrystals)—
Medium:
pH 7.2 (±0.05) phosphate buffer; 900 mL.
Apparatus 1:
100 rpm.
Times:
1, 3, and 8 hours.
Procedure—
Determine the amount of C
8H
6N
4O
5 dissolved by employing UV absorption at the wavelength of maximum absorbance at about 375 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 Nitrofurantoin RS in the same
Medium.
Tolerances—
The percentage of the labeled amount of C
8H
6N
4O
5 dissolved at the 1-hour point conforms to
Acceptance Table 2, and the percentages dissolved at the 3- and 8-hour points conform to the criteria for the final test time in
Acceptance Table 2.
| Time (hours) |
Amount dissolved |
| 1 |
between 20% and 60% |
| 3 |
not less than 45% |
| 8 |
not less than 60% |
TEST 2
(where it is labeled as containing both nitrofurantoin macrocrystalline and monohydrate forms)—If the product complies with this test, the labeling indicates that it meets USP
Dissolution Test 2.
Acid medium:
0.01 N hydrochloric acid for 1 hour; 900 mL.
pH 7.5 Buffer medium—
Prepare a pH 7.5 buffer concentrate by dissolving 62.2 g of potassium hydroxide and 129.3 g of monobasic potassium phosphate in water, dilute with water to 1 L, and mix. After 1 hour change the Acid medium to pH 7.5 Buffer medium by adding 50 mL of pH 7.5 buffer concentrate, for an additional 6 hours.
Apparatus 2:
100 rpm, with sinkers made of teflon-coated steel wire prepared by forming a coil approximately 22 mm long from a 13-cm length of 20-gauge wire (see
Figure 1).
Times:
1, 3, and 7 hours.
Acid-stage standard solution—
Prepare a solution of
USP Nitrofurantoin RS in
Acid medium to obtain a solution having a known concentration of about 0.025 mg per mL.
Buffer-stage standard solution—
Prepare a solution of
USP Nitrofurantoin RS in
pH 7.5 Buffer medium to obtain a solution having a known concentration of about 0.075 mg per mL.
Procedure—
Determine the amount of C8H6N4O5 dissolved from UV absorbances at the isosbestic wavelength at about 375 nm on filtered portions of each solution under test, suitably diluted, if necessary, with Acid medium or pH 7.5 Buffer medium when appropriate in comparison with the appropriate Standard solution.
Tolerances—
The percentages of the labeled amount of C
8H
6N
4O
5 dissolved at the specified times conform to the accompanying
Acceptance Table.
Time
(hours) |
Amount dissolved
(individual) |
Amount dissolved
(mean) |
| 1 |
between 2% and 16% |
between 5% and 13% |
| 3 |
between 27% and 69% |
between 39% and 56% |
| 7 |
not less than 68% |
not less than 81% |
Acceptance Table
| Level |
Number
Tested |
Criteria |
| L1 |
12 |
The mean percentage of dissolved label claim lies within the range for the means at each interval and is not less than the stated amount at the final test time. All individual values lie within the ranges for the individuals at each interval and are not less than the stated amount at the final test time. |
| L2 |
12 |
The mean percentage of dissolved label claim lies within the range for the means at each interval and is not less than the stated amount at the final test time. Not more than 2 of the 24 individual values lie outside the stated ranged for individuals at each interval, and not more than 2 of 24 are less than the stated amount at the final test time. |
(Official April 1, 2006)
Uniformity of dosage units 905:
meet the requirements.
Procedure for content uniformity—
Test solution—
Transfer the contents of 1 Capsule to a suitable flask, and add a volume of dimethylformamide to obtain a solution having a concentration of about 1.2 mg of nitrofurantoin per mL. Shake the flask for 15 minutes. [NOTE—If necessary, the sample may be homogenized using a disperser.] In the case of a 50- or 100-mg Capsule transfer 40.0 mL of this solution to a suitable flask, and proceed as directed for Assay preparation in the Assay, beginning with “add 50.0 mL of Internal standard solution.” In the case of a 25-mg Capsule, transfer 20.0 mL of the solution to a suitable flask, and add 25.0 mL of Internal standard solution instead of 50.0 mL.
Procedure—
Proceed as directed in the Assay, using the following Test solution instead of the Assay preparation.
Limit of nitrofurazone—
pH 7.0 Phosphate buffer, Mobile phase, Standard preparation, Chromatographic system, and Procedure—
Proceed as directed in the Limit of nitrofurazone test under Nitrofurantoin.
Test preparation—
Into a glass-stoppered, 25-mL flask weigh a portion of contents of Capsules equivalent to 100 mg of nitrofurantoin. Add 2.0 mL of dimethylformamide, and shake for 5 minutes. Add 20.0 mL of water, mix, and allow to stand for 15 minutes. Pass a portion of the mixture through a 0.45-µm pore size nylon filter.
Assay—
pH 7.0 phosphate buffer, Mobile phase, Internal standard solution, Standard preparation, and Chromatographic system—
Proceed as directed in the
Assay under
Nitrofurantoin.
Assay preparation—
Transfer, as completely as possible, the contents of 20 Capsules to a 500-mL flask. Place the emptied capsules in a beaker, add 25 mL of dimethylformamide, and agitate for 1 minute. Decant into the flask containing the Capsule contents. Rinse the emptied capsules with another two 25-mL portions of dimethylformamide, and decant into the flask. Add sufficient dimethylformamide to bring the volume to about 250 mL. Insert the stopper in the flask, and shake by mechanical means for 15 minutes. Dilute with dimethylformamide to volume, and mix. [NOTE—If necessary, the sample may be homogenized using a disperser.] Pass through a medium-porosity, sintered-glass filter into a suitable flask. Transfer an aliquot, equivalent to about 50 mg of nitrofurantoin, to a flask. Add an accurately measured volume of dimethylformamide to bring the volume in the flask to 40.0 mL. To the flask add 50.0 mL of Internal standard solution, mix, and cool to room temperature. Pass a portion of the solution through a 0.45-µm pore size nylon filter, discarding the first few mL of the filtrate.
Procedure—
Proceed as directed for
Procedure in the
Assay under
Nitrofurantoin. Calculate the quantity, in mg, of nitrofurantoin (C
8H
6N
4O
5) in the portion of the powder included in the sample aliquot by the formula:
W(RU / RS),
in which
W is the weight, in mg, of
USP Nitrofurantoin RS in the
Standard preparation; and
RU and
RS are the ratios of the peak responses of the nitrofurantoin to the internal standard obtained from the
Assay preparation and the
Standard preparation, respectively.
Auxiliary Information—
Staff Liaison :
Behnam Davani, Ph.D., MBA, Senior Scientist
Expert Committee : (MDAA05) Monograph Development-Antivirals and Antimicrobials
USP29–NF24 Page 1537
Pharmacopeial Forum : Volume No. 31(1) Page 170
Phone Number : 1-301-816-8394
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