Action and use
Central nervous system stimulant; nicotine replacement therapy.
DEFINITION
Nicotine Transdermal Patches contain Nicotine in a suitable matrix or reservoir presentation.
PRODUCTION
A suitable dissolution test is carried out to demonstrate the appropriate release of nicotine.
The transdermal patches comply with the requirements stated under Patches and with the following requirements.
Content of nicotine, C10H14N2
90.0 to 110.0% of the stated amount.
Carry out all of the following procedures protected from light.
IDENTIFICATION
Remove the protective liner from a patch, cut into small pieces and place a quantity of the patch containing 20 mg of Nicotine into a centrifuge tube, add 10 mL of chloroform, disperse with the aid of ultrasound for 30 minutes, cool and centrifuge for a further 10 minutes. Add 6 mL of 0.5M hydrochloric acid and centrifuge for 10 minutes. Transfer 5 mL of the aqueous layer to a separating funnel and adjust the pH to 10.5 with 0.5M sodium hydroxide. Extract with 3 mL of chloroform, shake and retain the chloroform layer. The infrared absorption spectrum of the solution, Appendix II A, is concordant with the reference spectrum of nicotine (RS 452).
TESTS
Related substances
Carry out the method for liquid chromatography, Appendix III D, using the following solutions in 0.2M potassium dihydrogen orthophosphate adjusted to pH 2.0 with orthophosphoric acid (solvent A).
(1) Remove the protective liner from a whole patch and cover the exposed surface with a porous material (glass wool or tissue may be suitable). Transfer the whole patch into a separating funnel containing 50 mL of hexane and shake for 10 minutes. Ensure that the layers in the patch are separated and shake for a further 10 minutes. Add 20 mL of solvent A and shake for a further 10 minutes. Remove the lower aqueous layer, dilute, if necessary with solvent A to give a concentration of approximately 0.04% w/v and filter through a 0.7-μm glass filter.
(2) Dilute 1 volume of solution (1) to 100 volumes.
(3) Dilute 1 volume of solution (2) to 10 volumes.
(4) 0.04% w/v of nicotine impurity standard BPCRS.
CHROMATOGRAPHIC CONDITIONS
(a) Use a stainless steel column (15 cm × 4.6 mm) packed with end-capped polar-embedded octadecylsilyl amorphous organosilica polymer (3.5 μm) (Waters XBridge is suitable) fitted with a guard column (3 cm × 4.6 mm) packed with the
same material.
(b) Use gradient elution and the mobile phase described below.
(c) Use a flow rate of 1.0 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 254 nm.
(f) Inject 20 μL of each solution.
MOBILE PHASE
Mobile phase A: Dilute 25 volumes of 1M acetic acid to 1000 volumes with water, add 6.2 volumes of 18M ammonia and adjust the pH to 10 with 18M ammonia.
Mobile phase B: acetonitrile.
In the chromatogram obtained with solution (4):
identify the peaks due to cotinine, myosmine, cis-nicotine-1′-oxide and trans-nicotine-1′-oxide.
In the chromatogram obtained with solution (1):
identify any peak corresponding to cis-nicotine-1′-oxide and multiply the area of this peak by a correction factor of 1.5;
identify any peak corresponding to trans-nicotine-1′-oxide and multiply the area of this peak by a correction factor of 1.5.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (4), the resolution between cotinine and trans nicotine-1′-oxide is at least 2.0.
LIMITS
In the chromatogram obtained with solution (1):
the area of any peak corresponding to cotinine is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (1.0%);
the area of any peak corresponding to myosmine is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (1.0%);
the area of any peak corresponding to cis-nicotine-1′-oxide is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (1.0%);
the area of any peak corresponding to trans-nicotine-1′-oxide is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (1.0%);
the area of any other secondary peak is not greater than 0.2 times the area of the principal peak in the chromatogram obtained with solution (2) (0.2%);
the sum of the areas of any other secondary peaks is not greater than the area of the principal peak in the chromatogram obtained with solution (2) (1.0%);
the sum of the areas of all secondary peaks is not greater than 3 times the area of the principal peak in the chromatogram obtained with solution (2) (3.0%).
Disregard any peak with an area less than the area of the principal peak in the chromatogram obtained with solution (3) (0.1%).
Uniformity of content
Comply with the requirements stated under Uniformity of content, Appendix XII C3, Test C, with respect to the individual content of each dosage unit and using the following method of analysis. Carry out the method for liquid chromatography,
Appendix III D, using the following solutions in solvent A described under Related substances test.
(1) Remove the protective liner from a whole patch and cover the exposed surface with a porous material (glass wool or tissue may be suitable). Transfer a whole patch into a separating funnel containing 50 mL of hexane and shake for 10 minutes. Ensure that the layers in the patch are separated and shake for a further 10 minutes. Add sufficient solvent A to produce a concentration of 0.04% w/v of nicotine and shake for a further 10 minutes. Remove the lower aqueous layer and
filter through a 0.7-μm glass filter. Dilute 1 volume of the resulting solution to 10 volumes with solvent A.
(2) 0.04% w/v of nicotine impurity standard BPCRS.
(3) 0.0124% w/v of nicotine ditartrate dihydrate BPCRS.
CHROMATOGRAPHIC CONDITIONS
The chromatographic conditions described under Related substances may be used.
SYSTEM SUITABILITY
The test is not valid unless, in the chromatogram obtained with solution (3), the resolution between trans-nicotine-1′-oxide and cotinine is at least 2.0.
DETERMINATION OF CONTENT
Calculate the content of C10H14N2 in the transdermal patch using the declared content of C10H14N2 in nicotine ditartrate dihydrate BPCRS. Each mg of C10H14N2 is equivalent to 3.074 mg of C10H14N2,C8H12O12,2H2O.
ASSAY
Use the average of the 10 results obtained in the test for Uniformity of content.
IMPURITIES
The impurities limited by the requirements of this monograph include those listed under Nicotine.
