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Effects of Iontophoresis and Chemical Enhancers on the Transport of Lidocaine and Nicotine Across the Oral Mucosa

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ABSTRACT

Purpose

To analyze the effects of chemical enhancers and iontophoresis on the buccal transmucosal delivery of lidocaine and nicotine.

Methods

Porcine oral mucosal samples were pretreated with chemical enhancers before conducting 8-hr Franz diffusion-cell experiments. In studies addressing the influence of iontophoresis on molecular transport, the current density was set at 0.3 mA/cm2. Data were analyzed using graphical and non-linear regression optimization techniques.

Results

Both permeation enhancement techniques promote drug transport. In the absence of electricity, the flux increased as high as 4- and 200-fold, relative to a control, in the case of lidocaine hydrochloride (LHCl) and nicotine hydrogen tartrate (NHT) gel formulations, respectively. The combination of iontophoresis and chemical enhancers produced an even higher flux compared to the original passive diffusion process: up to 8-fold for LHCl and 450-fold for NHT. Mostly, the current helped to decrease the response time. However, a balance should be maintained between reaching a high delivery rate and reducing the time it takes to attain a desired flux value. In addition, the influence of chemical enhancers was drug-specific.

Conclusions

The estimation of model parameters allows for a systematic approach to the design of chemical and physical penetration enhancers for transmucosal drug delivery.

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ACKNOWLEDGMENTS & DISCLOSURES

We thank NexMed (USA), Inc., San Diego, CA, USA for their generous gifts of the chemical enhancers DDAIP and DDAIP HCl. We also thank Iomed, Inc., Salt Lake City, UT for their donation of the Phoresor II Auto (model PM 850) devices to our laboratory. Peter J. Zhang from Ernest Mario School of Pharmacy, Rutgers-The State University of New Jersey, Piscataway, NJ is acknowledged for synthesizing the enhancer Br-iminosulfurane. New Jersey Center for Biomaterials, Rutgers-The State University of New Jersey, Piscataway, NJ, USA provided the azone for this study.

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Authors and Affiliations

  1. Otto H. York Dept. of Chemical, Biological & Pharmaceutical Engineering, New Jersey Institute of Technology, Newark, New Jersey, 07102, USA

    Ran Wei & Laurent Simon

  2. Ernest Mario School of Pharmacy, Rutgers—The State University of New Jersey, Piscataway, New Jersey, 08854, USA

    Longsheng Hu & Bozena Michniak-Kohn

Authors
  1. Ran Wei
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  2. Laurent Simon
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  3. Longsheng Hu
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  4. Bozena Michniak-Kohn
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Correspondence to Laurent Simon.

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Wei, R., Simon, L., Hu, L. et al. Effects of Iontophoresis and Chemical Enhancers on the Transport of Lidocaine and Nicotine Across the Oral Mucosa. Pharm Res 29, 961–971 (2012). https://doi.org/10.1007/s11095-011-0636-x

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  • DOI: https://doi.org/10.1007/s11095-011-0636-x

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