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Drug Delivery and Translational Research

, Volume 9, Issue 1, pp 319–333 | Cite as

Formulation and evaluation of carrier-free dry powder inhaler containing sildenafil

  • Thi-Tram Nguyen
  • Eun-Jin Yi
  • Kyu-Mok Hwang
  • Cheol-Hee Cho
  • Chun-Woong Park
  • Ju-Young Kim
  • Yun-Seok Rhee
  • Eun-Seok ParkEmail author
Original Article
  • 117 Downloads

Abstract

Pulmonary delivery of sildenafil for the treatment of pulmonary arterial hypertension could overcome the limitations of intravenous and oral administration routes, such as poor patient compliance and systemic side effects. In this study, a carrier-free dry powder inhaler (DPI) formulation was developed, using spray drying technique and L-leucine as a dispersibility enhancer. Sildenafil citrate salt and sildenafil free base were evaluated for drug transport using a Calu-3 cell model, and their suitability for DPI production by spray drying was tested. Characteristics of the resultant carrier-free DPI powders were examined, namely crystallinity, morphology, size distribution, density, zeta potential, and aerodynamic performance. A Box-Behnken design was adopted to optimize the formulation and process conditions, including leucine amount, fraction of methanol in spraying solvent, and inlet temperature. While both sildenafil forms exhibited sufficient permeability for lung absorption, only sildenafil base resulted in DPI powders which were stable for 6 months. The introduction of leucine into the formulations effectively enhanced aerodynamic performance of the powders and particles with favorable size, shape, and density were produced. The optimal DPI formulation determined from experimental design possesses excellent aerodynamic performance with 89.39% emitted dose and 80.08% fine particle fraction, indicating the possibility of incorporating sildenafil into carrier-free DPIs for pulmonary delivery.

Keywords

Pulmonary delivery Carrier-free DPI L-leucine Spray drying Calu-3 cells 

Notes

Funding

This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (grant number NRF-2016R1A2B400c7101).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Controlled Release Society 2018

Authors and Affiliations

  • Thi-Tram Nguyen
    • 1
  • Eun-Jin Yi
    • 1
  • Kyu-Mok Hwang
    • 1
  • Cheol-Hee Cho
    • 1
  • Chun-Woong Park
    • 2
  • Ju-Young Kim
    • 3
  • Yun-Seok Rhee
    • 4
  • Eun-Seok Park
    • 1
    Email author
  1. 1.School of PharmacySungkyunkwan UniversitySuwonRepublic of Korea
  2. 2.College of PharmacyChungbuk National UniversityCheongjuRepublic of Korea
  3. 3.College of PharmacyWoosuk UniversityWanju-gunRepublic of Korea
  4. 4.College of Pharmacy and Research Institute of Pharmaceutical SciencesGyeongsang National UniversityJinjuRepublic of Korea

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