We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Preformulation and Evaluation of Tofacitinib as a Therapeutic Treatment for Asthma.
- Authors
Younis, Usir S.; Vallorz, Ernest; Addison, Kenneth J.; Ledford, Julie G.; Myrdal, Paul B.
- 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.
- Publication
AAPS PharmSciTech, 2019, Vol 20, Issue 5, pN.PAG
- ISSN
1530-9932
- Publication type
Article
- DOI
10.1208/s12249-019-1377-0