Nitrofurantoin Capsules
»Nitrofurantoin Capsules contain not less than 90.0percent and not more than 110.0percent of the labeled amount of nitrofurantoin (C8H6N4O5).
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 1is not used.
Identification—
A:
Add 10mLof 6Nacetic acid to a quantity of the contents of Capsules,equivalent to about 100mg 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 1hour:the IRabsorption 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.
for 1hour:the IRabsorption 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 á711ñ—
TEST1
(where it is labeled as containing Nitrofurantoin macrocrystals)—
Medium:
pH7.2(±0.05)phosphate buffer;900mL.
Apparatus 1:
100rpm.
Times:
1,3,and 8hours.
Procedure—
Determine the amount of C8H6N4O5dissolved by employing UVabsorption at the wavelength of maximum absorbance at about 375nm 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 RSin the same Medium.
Tolerances—
The percentage of the labeled amount of C8H6N4O5dissolved at the 1-hour point conforms to Acceptance Table 1under Drug Release á724ñ,and the percentages dissolved at the 3-and 8-hour points conform to the criteria for the final test time in Acceptance Table 1under Drug Release á724ñ.
| Time (hours) | Amount dissolved |
| 1 | between 20%and 60% |
| 3 | not less than 45% |
| 8 | not less than 60% |
TEST2
(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 USPDissolution Test 2.
Acid medium:
0.01Nhydrochloric acid for 1hour;900mL.
pH7.5Buffer medium—
Prepare a pH7.5buffer concentrate by dissolving 62.2g of potassium hydroxide and 129.3g of monobasic potassium phosphate in water,dilute with water to 1L,and mix.After 1hour change the Acid mediumto pH7.5Buffer mediumby adding 50mLof pH7.5buffer concentrate,for an additional 6hours.
Apparatus 2:
100rpm,with sinkers made of teflon-coated steel wire prepared by forming a coil approximately 22mm long from a 13-cm length of 20-gauge wire (see Fig.1).
;)
Fig.1.Sinker.
Times:
1,3,and 7hours.
Acid-stage standard solution—
Prepare a solution of USP Nitrofurantoin RSin Acid medium to obtain a solution having a known concentration of about 0.025mg per mL.
Buffer-stage standard solution—
Prepare a solution of USP Nitrofurantoin RSin pH7.5Buffer medium to obtain a solution having a known concentration of about 0.075mg per mL.
Procedure—
Determine the amount of C8H6N4O5dissolved from UVabsorbances at the isosbestic wavelength at about 375nm on filtered portions of each solution under test,suitably diluted,if necessary,with Acid medium or pH7.5Buffer medium when appropriate in comparison with the appropriate Standard solution.
Tolerances—
The percentages of the labeled amount of C8H6N4O5dissolved 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 2of the 24individual values lie outside the stated ranged for individuals at each interval,and not more than 2of 24are less than the stated amount at the final test time. |
Change to read:
Uniformity of dosage units á905ñ:
meet the requirements.
Procedure for content uniformity—
Test solution—
Transfer the contents of 1Capsule to a suitable flask,and add a volume of dimethylformamide to obtain a solution having a concentration of about 1.2mg of nitrofurantoin per mL.Shake the flask for 15minutes.[
NOTE—If necessary,the sample may be homogenized using a disperser.]USP28In the case of a 50-or 100-mg Capsule transfer 40.0mLof this solution to a suitable flask,and proceed as directed for Assay preparationin the Assay,beginning with “add 50.0mLof Internal standard solution.”In the case of a 25-mg Capsule,transfer 20.0mLof the solution to a suitable flask,and add 25.0mLof Internal standard solutioninstead of 50.0mL.
NOTE—If necessary,the sample may be homogenized using a disperser.]USP28In the case of a 50-or 100-mg Capsule transfer 40.0mLof this solution to a suitable flask,and proceed as directed for Assay preparationin the Assay,beginning with “add 50.0mLof Internal standard solution.”In the case of a 25-mg Capsule,transfer 20.0mLof the solution to a suitable flask,and add 25.0mLof Internal standard solutioninstead of 50.0mL.
Procedure—
Proceed as directed in the Assay,using the following Test solutioninstead of the Assay preparation.
Limit of nitrofurazone—
pH7.0Phosphate buffer,Mobile phase,Standard preparation,Chromatographic system,andProcedure—
Proceed as directed in the Limit of nitrofurazonetest under Nitrofurantoin.
Test preparation—
Into a glass-stoppered,25-mLflask weigh a portion of contents of Capsules equivalent to 100mg of nitrofurantoin.Add 2.0mLof dimethylformamide,and shake for 5minutes.Add 20.0mLof water,mix,and allow to stand for 15minutes.Pass a portion of the mixture through a 0.45-µm pore size nylon filter.
Change to read:
Assay—
pH7.0phosphate buffer,Mobile phase,Internal standard solution,Standard preparation,andChromatographic system—
Proceed as directed in the Assayunder Nitrofurantoin.
Assay preparation—
Transfer,as completely as possible,the contents of 20Capsules to a 500-mLflask.Place the emptied capsules in a beaker,add 25mLof dimethylformamide,and agitate for 1minute.Decant into the flask containing the Capsule contents.Rinse the emptied capsules with another two 25-mLportions of dimethylformamide,and decant into the flask.Add sufficient dimethylformamide to bring the volume to about 250mL.Insert the stopper in the flask,and shake by mechanical means for 15minutes.Dilute with dimethylformamide to volume,and mix.[NOTE—If necessary,the sample may be homogenized using a disperser.]USP28Pass through a medium-porosity,sintered-glass filter into a suitable flask.Transfer an aliquot,equivalent to about 50mg of nitrofurantoin,to a flask.Add an accurately measured volume of dimethylformamide to bring the volume in the flask to 40.0mL.To the flask add 50.0mLof 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 mLof the filtrate.
NOTE—If necessary,the sample may be homogenized using a disperser.]USP28Pass through a medium-porosity,sintered-glass filter into a suitable flask.Transfer an aliquot,equivalent to about 50mg of nitrofurantoin,to a flask.Add an accurately measured volume of dimethylformamide to bring the volume in the flask to 40.0mL.To the flask add 50.0mLof 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 mLof the filtrate.
Procedure—
Proceed as directed for Procedurein the Assayunder Nitrofurantoin.Calculate the quantity,in mg,of nitrofurantoin (C8H6N4O5)in the portion of the powder included in the sample aliquot by the formula:
W(RU/RS),
in which Wis the weight,in mg,of USP Nitrofurantoin RSin the Standard preparation;and RUand RSare the ratios of the peak responses of the nitrofurantoin to the internal standard obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information—
Staff Liaison:Behnam Davani,Ph.D.,MBA,Senior Scientist
Expert Committee:(PA7)Pharmaceutical Analysis 7
USP28–NF23Page 1381
Pharmacopeial Forum:Volume No.30(1)Page 139
Phone Number:1-301-816-8394