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 range for individuals at each interval, and not more than 2 of 24 are less than the stated amount at the final test time. |
Test 3
(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 3.
Acid medium, pH 7.5 Buffer medium, Apparatus 2, Times, Acid-stage standard solution, Buffer-stage standard solution, and Procedure—
Proceed as directed for Test 2.
Tolerances—
The percentages of the labeled amount of C
8H
6N
4O
5 dissolved at the specified times conform to
Acceptance Table 2.
Time
(hours) |
Amount dissolved
(individual) |
Amount dissolved
(mean) |
| 1 |
between 2% and 16% |
between 5% and 13% |
| 3 |
between 50% and 80% |
between 55% and 75% |
| 7 |
not less than 85% |
not less than 90% |
Test 4
(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 4.
Acid medium:
0.01 N hydrochloric acid for 1 hour; 900 mL, deaerated.
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, and run for an additional 9 hours.
Apparatus 2:
100 rpm, with helix sinkers.
Times:
1, 3, and 10 hours.
Stock standard solution—
Transfer about 25 mg, accurately weighed, of
USP Nitrofurantoin RS to a 10-mL volumetric flask. Add 7.5 mL of dimethylformamide, and sonicate until dissolved. Allow to cool to room temperature, dilute with dimethylformamide to volume, and mix.
Acid-stage standard solution—
Transfer 2.0 mL of the Stock standard solution to a 200-mL volumetric flask. Dilute with Acid medium to volume, and mix.
Buffer-stage standard solution—
Transfer 3.0 mL of the Stock standard solution to a 100-mL volumetric flask. Add 5.6 mL of pH 7.5 buffer concentrate, dilute with Acid medium to volume, and mix.
Stock capsule shell blank—
Place 10 empty, clean capsules into a 900-mL volumetric flask. Add approximately 800 mL of
Acid medium. Gently heat to 37 ± 0.5
, and stir until all the capsules are dissolved. Allow to cool to room temperature, dilute with
Acid medium to volume, and mix.
Acid-stage capsule shell blank—
Transfer 100.0 mL of the Stock capsule shell blank to a 1000-mL volumetric flask, dilute with Acid medium to volume, and mix. Filter using the same filter as for the Test solution.
Buffer-stage capsule shell blank—
Transfer 100.0 mL of the Stock capsule shell blank to a 1000-mL volumetric flask. Add 56 mL of pH 7.5 buffer concentrate, dilute with Acid medium to volume, and mix. Filter using the same filter as for the Test solution.
Test solution—
Pass portions of the solution under test through a 1.2-µm glass/0.45-µm polyethersulfone combination filter, discarding the first few mL.
Procedure—
Determine the amount of C8H6N4O5 dissolved by UV/Vis absorption at the wavelength of maximum absorbance at about 375 nm on portions of the Test solution in comparison with the appropriate Acid- or buffer-stage standard solution. Correct for the appropriate capsule shell blank absorbance, using a 0.1 cm cell, and the appropriate medium as blank.
Tolerances—
The percentages of the labeled amount of C
8H
6N
4O
5 dissolved at specified times conform to
Acceptance Table 2.
| Time (hours) |
Amount dissolved |
| 1 |
not more than 25% |
| 3 |
between 25% and 50% |
| 10 |
not less than 80% |
711
—
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;)