The purpose of this experiment was to illustrate the ruggedness of drug release from a Nicotine Transdermal System Patch when subjected to various potential misuse conditions, by measuring the impact of these conditions on the in vitro release profile of the product. Transdermal delivery of drugs is a growing alternative to oral delivery, as well as hypodermic injection. The first transdermal system (Scopolamine) was approved in 1979, and the first transdermal smoking cessation therapies were approved in 1991 (Nicoderm, Habitrol, and ProStep). 1 Smoking cessation therapies have continued to make common use of this drug delivery mechanism.
Nicotine Transdermal System (Rugby® Step One, 21 mg delivered over 24 hours) patches were subjected to in vitro dissolution using USP Apparatus V (paddle over disk) at 50 rpm in 900 mL of media at 32.0°C ± 0.3°C, at time points ranging from 15 minutes to a maximum of 6 hours, as well as following manipulation to simulate potential misuse. Samples were subjected to dissolution at pH levels of 1.2, 4.5, and 6.8, as indicated in the bioequivalence guidance for the product2 , along with the release conditions specified in the USP monograph for Test 33 . In order to simulate potential misuse of the product, additional product treatment conditions of a lotion pre-treatment (obstruction from other dermal products), saline pre-wetting (sweaty skin), a torn patch, as well as incomplete removal of the protective layer from the patch (obstructions on the skin), were assessed in water as a medium. Sample concentrations were determined by HPLC, based on conditions from the USP monograph, using an Agilent 1100 equipped with a Sunfire C18 4.6 x 250 mm, 5µm column, using 70/30 water:acetonitrile mobile phase with 0.1% triethylamine at a flow rate of 1.0 mL/min, with a variable wavelength detector set at 260 nm, and a 10µL injection volume with a run time of 12 min. Samples were evaluated relative to the release specifications noted in the USP monograph (35-75% at 1 hour, 55-95% at 2 hours, and not less than 73% at 4 hours), as a benchmark for the results of this study.
Patches at the in vitro dissolution conditions indicated in the bioequivalence guidance, as well as the USP monograph, met the acceptance criteria for release (Figure 1).
This indicates appropriate conduct of the in vitro dissolution and quantitation, and provides a baseline against which the potential misuse conditions can be compared. When subjected to various potential misuse conditions, it was noted that the lotion, saline, and tearing did not cause the release profile of the patches to fail to meet the criteria of the USP monograph. Only the partial or fully covered patches failed to meet the release criteria. See Figure 2 for the dissolution profiles.
Conditions for testing were appropriate, as demonstrated by successful release profiles of unadulterated patches.
The transdermal system examined (Rugby® Step One, 21 mg delivered over 24 hours) are robust to various potential misuse conditions (sweat, oil/lotion, wetting, and tearing).
The only conditions noted in this study that would impact proper release were when the patches are obstructed from full contact from the skin.
1. Prausnitz, M.R., Langer, R. Transdermal Drug Delivery. Nature Biotechnology. 26, 1261‐1268 (2008).
2. Draft Guidance on Nicotine. Food and Drug Administration. Recommended November 2013; Revised October 2016.
3. Nicotine Transdermal System. United States Pharmacopeia and National Formulary (USP 40‐NF 35). Rockville, MD: United States Pharmacopeia Convention; 2017: 5345‐5347.
Myers, Adam C.; Guerra, Justin; Hasler, Ashlee. Robustness of Drug Release from Transdermal Patches. Poster Presentation. AAPS National Meeting, San Diego, CA, November 12-16, 2017.