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AAPS PharmSciTech

, 20:167 | Cite as

Preformulation and Evaluation of Tofacitinib as a Therapeutic Treatment for Asthma

  • Usir S. YounisEmail author
  • Ernest Vallorz
  • Kenneth J. Addison
  • Julie G. Ledford
  • Paul B. Myrdal
Research Article Theme: Paul Myrdal Memorial Issue - Pharmaceutical Formulation and Aerosol Sciences
  • 97 Downloads
Part of the following topical collections:
  1. Theme: Paul Myrdal Memorial Issue - Pharmaceutical Formulation and Aerosol Sciences

Abstract

Preformulation studies on tofacitinib citrate, a small molecule JAK3 specific inhibitor, have not been previously reported in literature. We therefore conducted several preformulation studies on tofacitinib citrate, and its free base, to better understand factors that affect its solubility, stability, and solid-state characteristics. Further, the results of the preformulation studies helped facilitate the development of a nebulized formulation of tofacitinib citrate for inhalational delivery to house dust mite allergen-challenged, BALB/c mice as a potential treatment for eosinophilic asthma. The preformulation results indicated tofacitinib having a basic pKa of 5.2, with its stability dependent on pH, ionic strength, and temperature. Degradation of tofacitinib follows apparent first-order kinetics. In order to maximize stability of the drug, ionic strength and temperature should be minimized, with an optimal range pH between 2.0 and 5.0. Additionally, our findings demonstrate that tofacitinib citrate can successfully be nebulized at a suitable droplet size for inhalation (1.2 ± 0.2 μm MMAD) through a nose-only chamber. Animals dosed with tofacitinib citrate demonstrated marked reductions in BAL eosinophils and total protein concentrations following HDM challenge. These data suggest that tofacitinib citrate represents the potential to be an effective therapy for eosinophilic asthma.

KEY WORDS

tofacitinib tofacitinib citrate inhalational delivery eosinophilia asthma 

Notes

Acknowledgements

We would like to thank the American Foundation of Pharmaceutical Education (AFPE) for providing Usir Younis with the Lynn Van Campen Award in Formulation Design, Pre-Doctoral Fellowship for 2 years to help fund this research.

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Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Usir S. Younis
    • 1
    • 2
    Email author
  • Ernest Vallorz
    • 3
  • Kenneth J. Addison
    • 4
  • Julie G. Ledford
    • 4
    • 5
  • Paul B. Myrdal
    • 1
  1. 1.Department of Pharmaceutical SciencesUniversity of ArizonaTucsonUSA
  2. 2.Biosciences Research Laboratories (BSRL) BuildingTucsonUSA
  3. 3.Department of Pharmacology and ToxicologyUniversity of ArizonaTucsonUSA
  4. 4.Department of Cellular and Molecular MedicineUniversity of ArizonaTucsonUSA
  5. 5.Asthma and Airways Disease Research CenterUniversity of ArizonaTucsonUSA

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