Nicotine Transdermal System
» Nicotine Transdermal System contains not less than 90.0 percent and not more than 110.0 percent of the labeled amount of nicotine (C10H14N2).
Packaging and storage
Preserve in the hermetic, light-resistant, unit-dose pouch.
Labeling
The labeling indicates the Drug Release Test with which the product complies.
Identification
The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
Drug release 724
test 1
If the product complies with this test, the labeling indicates that it meets USP Drug Release Test 1.
Medium:
Phosphoric acid solution (1 in 1000); 250 mL, in a tall-form beaker.
Apparatus 7
Proceed as directed in the chapter, using the transdermal system holdercylinder (see Figure 4b). Center the Transdermal System onto a dry, unused 10-cm × 10-cm piece of Cuprophan dialysis membrane with the adhesive side against the membrane, taking care to eliminate air bubbles between the membrane and the release surface. Attach the membrane to the cylinder using two Parker O-rings, such that one of the borders of the transdermal system is aligned to the groove and it is wrapped around the cylinder. The filled beakers are weighed and pre-equilibrated to 32.0 ± 0.3, prior to immersing the test sample. Reciprocate at a frequency of about 30 cycles per minute with an amplitude of 2.0 ± 0.1 cm. At the end of each time interval, transfer the test sample to a fresh beaker containing the appropriate volume of Medium, weighed and pre-equilibrated to 32.0 ± 0.3. At the end of each release interval, allow the beakers to cool to room temperature, make up for evaporative losses by adding water to obtain the original weight, and mix. This solution is the final Test solution.
Times:
2, 12, and 24 hours.
Determine the amount of C10H14N2 released by employing the following method.
Mobile phase
Transfer 0.2 mL of N,N-dimethyloctylamine to a 1-L volumetric flask, add 220 mL of acetonitrile, and mix. Add 300 mL of water, 0.2 mL of glacial acetic acid, 0.20 g of anhydrous sodium acetate, and 0.55 g of sodium 1-dodecanesulfonate, and dilute with water to volume. Mix for 1 hour until clear. Filter and degas. Make adjustments if necessary (see System Suitability under Chromatography 621). [noteEquilibration of the column may take as long as 3 hours.]
Standard solution
Dissolve an accurately weighed quantity of USP Nicotine Bitartrate Dihydrate RS in Medium, and dilute quantitatively, and stepwise if necessary, with Medium to obtain a solution having a known concentration of about 0.142 mg of nicotine bitartrate per mL (or 0.046 mg nicotine as free base per mL). [noteAbout 80 mL of this solution is required in order to prepare the System suitability solution.]
System suitability solution
Transfer 8 mg (free base) of nicotine to a 100-mL volumetric flask, and dissolve in 10 mL of acetonitrile. Add 5 mL of 30% hydrogen peroxide, and allow 15 minutes to react. Dilute with Medium to volume, and mix. Transfer 20 mL of this solution to a 100-mL volumetric flask, dilute with Standard solution to volume, and mix.
Chromatographic system (see Chromatography 621)
The liquid chromatograph is equipped with a 254-nm detector and a 4.6-mm × 15-cm column that contains packing L1. The flow rate is about 1 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the resolution, R, between nicotine and any degradation peaks is not less than 1.1; the tailing factor is not more than 2.0; and the relative standard deviation for replicate injections is not more than 1.5%.
Procedure
Separately inject equal volumes (about 50 µL) of filtered portions of the Standard solution and the solution under test into the chromatograph, record the chromatograms, and measure the responses for the major peaks.
Tolerances
The amount of C10H14N2 released, as a percentage of the labeled amount of the dose absorbed in vivo, at the times specified below, conforms to Acceptance Table 1.
test 2
If the product complies with this test, the labeling indicates that it meets USP Drug Release Test 2.
Phosphate buffer
Dissolve 40.0 g of sodium chloride, 1.0 g of potassium chloride, 8.66 g of dibasic sodium phosphate, and 1.0 g of monobasic potassium phosphate in 5 L of water.
Medium:
Phosphate buffer; 500 mL.
Apparatus 6:
50 rpm, double-sided tape being used to attach the Transdermal System to the cylinder.
Times:
6 and 24 hours.
Determine the amount of C10H14N2 released by employing the following method.
Mobile phase
Proceed as directed in the Assay.
System suitability solution
Transfer 1.0 mL of the System suitability solution, prepared as directed in the Assay, to a 100-mL volumetric flask, dilute with Medium to volume, and mix.
Standard solution
Pipet 6.0 mL of the Standard preparation, prepared as directed in the Assay, into a 50-mL volumetric flask, dilute with Medium to volume, and mix. Dilute quantitatively and stepwise with Medium to obtain an appropriate final concentration.
Test solution
At each of the test times, withdraw a 2-mL aliquot of the solution under test. [noteReplace the aliquots withdrawn for analysis with fresh portions of Medium.]
Chromatographic system (see Chromatography 621)
The liquid chromatograph is equipped with a 260-nm detector and a 4.6-mm × 12.5-cm column that contains packing L1. The flow rate is about 1 mL per minute. Chromatograph the Standard solution used for the 6-hour interval, and record the peak responses as directed for Procedure: the resolution, R, between 4,4¢-dipyridyl and nicotine is not less than 5.0; 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 100 µL) of the filtered portion of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the responses for the major peaks.
Tolerances
The amount of C10H14N2 released, as a percentage of the labeled amount of the dose absorbed in vivo, at the times specified, conforms to Acceptance Table 1.
test 3
If the product complies with this test, the labeling indicates that it meets USP Drug Release Test 3.
Medium:
water; 900 mL.
Apparatus 5:
50 rpm, the stainless steel disk assembly being replaced with a 5-cm watch glass for an 11-mg Transdermal System and an 8-cm watch glass for a 22-mg Transdermal System.
Times:
1, 2, and 4 hours.
Standard solution
Prepare a solution of USP Nicotine Bitartrate Dihydrate RS in water having a known concentration of nicotine similar to that of the solution under test.
Procedure
Determine the amount of C10H14N2 released by employing UV absorption at the wavelength of maximum absorbance at about 259 nm, in comparison with the Standard solution, using water as the blank.
Tolerances
The amount of C10H14N2 released, as a percentage of the labeled amount of the dose absorbed in vivo, at the times specified, conforms to the following Acceptance Table.
Acceptance Table
test 4
If the product complies with this test, the labeling indicates that it meets USP Drug Release Test 4.
Medium:
0.025 N hydrochloric acid; 600 mL.
Apparatus 5:
50 rpm, a convex screen being used to hold the Transdermal System in position during testing.
Times:
4 and 16 hours.
Standard solution and Procedure
Proceed as directed under Test 3.
Tolerances
The amount of C10H14N2 released, as a percentage of the labeled amount of the dose absorbed in vivo, at the times specified, conforms to Acceptance Table 1.
test 5
If the product complies with this test, the labeling indicates that it meets USP Drug Release Test 5.
Phosphate buffer, Medium, and Apparatus
Proceed as directed under Test 2.
Times:
3, 6, and 24 hours.
Mobile phase
Proceed as directed in the Assay.
System suitability solution, Standard solution, Test solution, and Chromatographic system
Proceed as directed under Test 2.
Procedure
Proceed as directed under Test 2 except to inject about 30 µL.
Tolerances
The amount of C10H14N2 released, as a percentage of the labeled amount of the dose absorbed in vivo, at the times specified, conforms to Acceptance Table 1.
Uniformity of dosage units 905:
meets the requirements.
Assay
Mobile phase
Mix 300 mL of acetonitrile, 700 mL of water, and 1 mL of triethylamine, filter, and degas. Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation
Dissolve an accurately weighed quantity of USP Nicotine Bitartrate Dihydrate RS in water to obtain a stock solution having a known concentration of about 26.87 mg per mL. Quantitatively dilute a volume of the stock solution with methanol to obtain a solution having a known concentration of about 5.37 mg of USP Nicotine Bitartrate Dihydrate RS per mL. [noteThis solution contains 1.75 mg of nicotine per mL.]
System suitability solution
Transfer about 8 mg of 4,4¢-dipyridyl to a 25-mL volumetric flask, add 5.0 mL of the Standard preparation, dilute with methanol to volume, and mix.
Assay preparation
Cut an accurately counted number of Transdermal Systems, equivalent to about 175 mg of nicotine, based on the label claim, into strips 5 cm2 in area. Remove the protective liners, if any, from the strips, and discard. Transfer the strips to a 250-mL flask, and add 100.0 mL of methanol. Insert the stopper into the flask, and shake by mechanical means for about 3 hours. Filter, and use the clear filtrate as the Assay preparation.
Chromatographic system (see Chromatography 621)
The liquid chromatograph is equipped with a 260-nm detector and a 4.6-mm × 25-cm column containing packing L1. The flow rate is about 1.5 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the resolution, R, between nicotine and 4,4¢-dipyridyl is not less than 5.0. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 1.0%.
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 areas for the major peaks. Calculate the percent label claim of nicotine (C10H14N2) in each Transdermal System taken by the formula:
100(162.23/462.41)(CS / CU)(rU / rS)
in which 162.23 and 462.41 are the molecular weights of nicotine and anhydrous nicotine bitartrate, respectively; CS is the concentration, in mg per mL, of USP Nicotine Bitartrate Dihydrate RS in the Standard preparation; CU is the nominal concentration of nicotine in the Assay preparation, based on the label claim; and rU and rS are the nicotine peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information
Please check for your question in the FAQs before contacting USP.
Chromatographic Column
USP32NF27 Page 3079
Pharmacopeial Forum: Volume No. 33(5) Page 927
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.
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