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Influence of Critical Parameters of Nanosuspension Formulation on the Permeability of a Poorly Soluble Drug through the Skin—A Case Study

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Abstract

In transdermal drug delivery systems, it is always a challenge to achieve stable and prolonged high permeation rates across the skin since the concentrations of the drug dissolved in the matrix have to be high in order to maintain zero order release kinetics. Several attempts have been reported to improve the permeability of poorly soluble drug compounds using supersaturated systems. However, due to thermodynamic challenges, there was a high tendency for the drug to nucleate immediately after formulating or even during storage. The present study focuses on the efficiency of nanoparticles and influence of different concentrations of solubilizer such as vitamin E TPGS (d-a-tocopheryl polyethylene glycol 1000 succinate) to improve the permeation rate through the skin. Effects of several formulation factors were studied on the nanosuspension systems using ibuprofen as a model drug. The overall permeation enhancement process through the skin was influenced mostly by the solubilizer and also by the size of nanoparticles. The gel formulation developed with vitamin E TPGS + HPMC nanosuspension, consequently represent a promising approach aiming to improve the permeability performance of a poorly water soluble drug candidate.

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Acknowledgments

The authors would like to thank Theresa Bello, Ami Shah, Hakim Robinson (Ernest Mario School of Pharmacy) and Joshua Wang (Biomedical Engineering) for their support with the permeation experiments and HPLC studies. The author would also like to thank Victoria Kai (Novartis Pharmaceuticals) for her support with the MVDA studies.

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Authors and Affiliations

  1. Ernest Mario School of Pharmacy, Rutgers-The State University of NJ, Piscataway, New Jersey, USA

    Indrajit Ghosh & Bozena Michniak-Kohn

  2. Novartis Pharmaceuticals Corporation, One Health Plaza, East Hanover, New Jersey, USA

    Indrajit Ghosh

  3. Celgene Corporation, Basking Ridge, New Jersey, USA

    Indrajit Ghosh

Authors
  1. Indrajit Ghosh
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  2. Bozena Michniak-Kohn
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Correspondence to Bozena Michniak-Kohn.

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Ghosh, I., Michniak-Kohn, B. Influence of Critical Parameters of Nanosuspension Formulation on the Permeability of a Poorly Soluble Drug through the Skin—A Case Study. AAPS PharmSciTech 14, 1108–1117 (2013). https://doi.org/10.1208/s12249-013-9995-4

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  • DOI: https://doi.org/10.1208/s12249-013-9995-4

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