Worth Longest, Ph.D.

Louis S. and Ruth S. Harris Exceptional Scholar Professor, Department of Mechanical and Nuclear Engineering

  • Engineering East Hall, Room E3248, Richmond VA UNITED STATES

Professor Longest works to address significant current challenges in the field of medical aerosols


Areas of Expertise

Infant Aerosol Delivery
Targeting Inhaled Medications within the Lungs
Inhaled Medications
Respiratory Drug Delivery
Particle Engineering
Inhaler Design and Development
Pediatric Aerosol Delivery
Inhaled Antibiotics
Inhaled Surfactants
Inhaled Anti-inflammatories
Computational Fluid Dynamics
Pharmacutical Aerosol Product Development Pipeline
Transport Theory
Realistic In Vitro Aerosol Testing
Development of Inhaled Generic Medications


Editorial Board Membership


Journal of Aerosol Science

Editorial Board Membership


Journal of Aerosol Medicine and Pulmonary Drug Delivery

Louis S. and Ruth S. Harris Exceptional Scholar Professor


Endowed Professorship

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North Carolina State University


Mechanical Engineering


North Carolina State University


Mechanical Engineering


North Carolina State University


Mechanical Engineering


Selected Articles

Initial Development of an Air-Jet Dry Powder Inhaler for Rapid Delivery of Pharmaceutical Aerosols to Infants

Journal of aerosol medicine and pulmonary drug delivery 34 (1), 57-70

C Howe, M Hindle, S Bonasera, V Rani, PW Longest


Background: Positive-pressure dry powder inhalers (DPIs) have recently been developed that in combination with highly dispersible spray-dried powder formulations can achieve high efficiency aerosolization with low actuation air-volumes (AAVs). The objective of this study was to initially develop the positive-pressure air-jet DPI platform for high efficiency aerosol delivery to newborn infants by using the nose-to-lung route.

Methods: Aerosolization performance metrics of six air-jet DPIs were first assessed at AAVs that were consistent with full-term (30 mL) and preterm (10 mL) neonates. Designs of the air-jet DPIs varied based on geometry of the inlet and outlet flow passages and shape of the aerosolization chamber. Aerosolization metrics evaluated at the device outlet were emitted dose (ED) and mass median aerodynamic diameter (MMAD). Designs with the best aerosolization performance were connected to a smoothly expanding nasal interface and full-term infant (3550 g) nose-throat (NT) model with tracheal filter.

Results: The three best performing devices had characteristics of a cylindrical and horizontal aerosolization chamber with a flush or protruding outlet orifice. Including multiple air inlets resulted in meeting the aerosolization targets of >80% ED (based on loaded dose) and MMAD

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Characterization of excipient enhanced growth (EEG) tobramycin dry powder aerosol formulations

International Journal of Pharmaceutics 591, 120027

A Hassan, D Farkas, W Longest, M Hindle


Spray drying can be utilized to produce highly dispersible powder aerosol formulations. However, these formulations are known to be hygroscopic, leading to potential solid-state stability and aerosol performance issues. This study aims to investigate if control of the spray drying particle formation conditions could be employed to improve the solid-state stability and alter the aerosol performance of tobramycin EEG formulations. Eight formulations were prepared, each had the same drug:excipient ratio of 60%w/w tobramycin, 20% w/w l-leucine, 18% w/w mannitol, and 2% w/w poloxamer 188. An experimental design matrix was performed with drying air water content of 1 or 10 g/m3 and spray drying solution l-leucine concentrations of 4.6, 7.6, 15.2 or 23.0 mmol/L. The particle size, morphology and crystallinity of spray dried formulations were characterized together with their dynamic moisture vapor sorption and aerosol performance. Higher crystallization and glass transition %RH were observed for the formulations spray dried using drying air with higher water content indicating more stable characteristics. Initial screening using a handheld dry powder inhaler of the realistic aerosol performance revealed that neither changing l-leucine concentration nor the drying gas water content affect the in-vitro expected lung dose. However, using a novel positive pressure inhaler, formulations produced using spray drying solutions with lower l-leucine concentrations showed better aerosol performance with MMAD around 2 µm and FPF < 5 µm around 80%.

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Excipient Enhanced Growth Aerosol Surfactant Replacement Therapy in an In Vivo Rat Lung Injury Model

Journal of aerosol medicine and pulmonary drug delivery 33 (6), 314-322

Franck J Kamga Gninzeko, Michael S Valentine, Cindy K Tho, Sahil R Chindal, Susan Boc, Sneha Dhapare, Mohammad Abdul Motalib Momin, Amr Hassan, Michael Hindle, Dale R Farkas, P Worth Longest, Rebecca L Heise


Background: In neonatal respiratory distress syndrome, breathing support and surfactant therapy are commonly used to enable the alveoli to expand. Surfactants are typically delivered through liquid instillation. However, liquid instillation does not specifically target the small airways. We have developed an excipient enhanced growth (EEG) powder aerosol formulation using Survanta®.

Methods: EEG Survanta powder aerosol was delivered using a novel dry powder inhaler via tracheal insufflation to surfactant depleted rats at nominal doses of 3, 5, 10, and 20 mg of powder containing 0.61, 0.97, 1.73, and 3.46 mg of phospholipids (PL), whereas liquid Survanta was delivered via syringe instillation at doses of 2 and 4 mL/kg containing 18.6 and 34 mg of PL. Ventilation mechanics were measured before and after depletion, and after treatment. We hypothesized that EEG Survanta powder aerosol would improve lung mechanics compared with instilled liquid Survanta in surfactant depleted rats.

Results and Conclusion: EEG Survanta powder aerosol at a dose of 0.61 mg PL significantly improved lung compliance and elastance compared with the liquid Survanta at a dose of 18.6 mg, which represents improved primary efficacy of the aerosol at a 30-fold lower dose of PL. There was no significant difference in white blood cell count of the lavage from the EEG Survanta group compared with liquid Survanta. These results provide an in vivo proof-of-concept for EEG Survanta powder aerosol as a promising method of surfactant replacement therapy.

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