A Comparison among Three Skin Preparations for the Transdermal Delivery of Vitamin B12 by Iontophoresis: A Novel Approach to Determine Systemic Absorption

Background: Poor skin permeability precludes the use of the transdermal route for the administration of most medications that require entry into the systemic circulation. However, charged compounds may be delivered systemically by Iontophoresis (ION). The relative safety and efficacy of the transdermal delivery of vitamin B12 (Methylcobalamin) by ION was determined by testing three different skin preparations. Subjects and Methods: Vitamin B12 15 mg was transdermally administered to 8 healthy subjects after the skin was prepared for ION delivery by three methods that were performed on each subject in a random order 1. Cleaning the skin with isopropyl alcohol (control) 2. Epilation followed by cleaning the skin with isopropyl alcohol 3. Pre-soaking the skin with oleic acid followed by cleaning the skin with isopropyl alcohol. The serum vitamin B12 concentration was determined by chemiluminescence methodology (Advia Centaur-XP). Blood was drawn immediately prior to and 10 min after each vitamin B12 administration, with the latter blood collection 30 min after the initiation of ION. The serum vitamin B12 absorbed systemically by transdermal ION was calculated from the measured rise in the serum concentration and the estimated blood volume. Results: The control group had an average of 5.8% (0.88 ± 0.90 mg; p<0.05) of vitamin B12 systemically absorbed. Epilation prior to ION was the most effective method to facilitate delivery of vitamin B12 with the average vitamin B12 systemically absorbed of at least 26.5% (3.97 ± 3.25 mg; p<0.005). The method of pre-soaking the skin with oleic acid was the least effective to promote absorption of vitamin B12 with 1.87% systemically absorbed (0.28 ± 0.28 mg; p<0.05). Minor, transient skin irritation was the only adverse reaction observed. Conclusion: Epilation prior to transdermal ION administration of vitamin B12 achieved the greatest delivery of agent of the three skin preparation methods tested. However, the transdermal administration of agent after only cleaning the skin with alcohol offered reasonably adequate systemic delivery with less preparatory effort and without the discomfort associated with epilation. Because of the variability in drug absorption among individuals, the anticipated systemic dose of a positively charged compound of similar molecular weight delivered by ION may be safely estimated by measuring the absorption of vitamin B12.