Worth Longest, Ph.D. profile photo

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

pwlongest@vcu.edu

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

Media

Publications

Documents

Audio

Video

Social

Areas of Expertise

Infant Aerosol DeliveryTargeting Inhaled Medications within the LungsInhaled MedicationsRespiratory Drug DeliveryParticle EngineeringInhaler Design and DevelopmentPediatric Aerosol DeliveryInhaled AntibioticsInhaled SurfactantsInhaled Anti-inflammatoriesComputational Fluid DynamicsPharmacutical Aerosol Product Development PipelineTransport TheoryRealistic In Vitro Aerosol TestingDevelopment of Inhaled Generic Medications

Accomplishments

Editorial Board Membership | professional

Journal of Aerosol Science

2019-03-07

Editorial Board Membership | professional

Journal of Aerosol Medicine and Pulmonary Drug Delivery

2018-06-01

Louis S. and Ruth S. Harris Exceptional Scholar Professor | professional

Endowed Professorship

2017-08-01

Fellow, American Institute for Medical and Biological Engineering

2015

Qimonda Assistant/Associate Professor of Mechanical Engineering Endowed Professorship

2007 - 2010

Graduate Assistance in Areas of National Need (GAANN) Fellowship

2000 - 2001

United Technologies Graduate Engineering Award

2001

NSF Graduate Research Trainee Fellowship in Scientific Computation

1998 - 1999

North Carolina Supercomputing Center Cray/SGI Fellowship

1999

U.S. Environmental Protection Agency Complimentary Service Award

1998

Education

North Carolina State University

Ph.D., Mechanical Engineering

2002

North Carolina State University

M.S., Mechanical Engineering

1999

North Carolina State University

B.S., Mechanical Engineering

1996

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

2021-01-05

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

2021-02-09

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

2021-03-17

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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High-efficiency dry powder aerosol delivery to children: Review and application of new technologies Authors Karl Bass, Dale Farkas, Amr Hassan | Journal of Aerosol Science, 105692

2020-12-15

K Bass, D Farkas, A Hassan, S Bonasera, M Hindle, W Longest

While dry powder aerosol formulations offer a number of advantages, their use in children is often limited due to poor lung delivery efficiency and difficulties with consistent dry powder inhaler (DPI) usage. Both of these challenges can be attributed to the typical use of adult devices in pediatric subjects and a lack of pediatric-specific DPI development. In contrast, a number of technologies have recently been developed or progressed that can substantially improve the efficiency and reproducibility of DPI use in children including: (i) nose-to-lung administration with small particles, (ii) active positive-pressure devices, (iii) structures to reduce turbulence and jet momentum, and (iv) highly dispersible excipient enhanced growth particle formulations. In this study, these technologies and their recent development are first reviewed in depth. A case study is then considered in which these technologies are simultaneously applied in order to enable the nose-to-lung administration of dry powder aerosol to children with cystic fibrosis (CF). Using a combination of computational fluid dynamics (CFD) analysis and realistic in vitro experiments, device performance, aerosol size increases and lung delivery efficiency are considered for pediatric-CF subjects in the age ranges of 2–3, 5–6 and 9–10 years old. Results indicate that a new 3D rod array structure significantly improves performance of a nasal cannula reducing interface loss by a factor of 1.5-fold and produces a device emitted mass median aerodynamic diameter (MMAD) of 1.67 μm. For all ages considered, approximately 70% of the loaded dose reaches the lower lung beyond the lobar bronchi. Moreover, significant and rapid size increase of the aerosol is observed beyond the larynx and illustrates the potential for targeting lower airway deposition. In conclusion, concurrent CFD and realistic in vitro analysis indicates that a combination of multiple new technologies can be implemented to overcome obstacles that currently limit the use of DPIs in children as young as two years of age.

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Linking Suspension Nasal Spray Drug Deposition Patterns to Pharmacokinetic Profiles: A Proof-of-Concept Study Using Computational Fluid Dynamics | Journal of Pharmaceutical Sciences

2016

With the steadily increasing price of medications in the US market, the introduction of cost-effective generic products is typically viewed as favorable for consumers. For a generic pharmaceutical nasal spray suspension formulation to enter the marketplace, a demonstration of bioequivalence between an innovator and the generic product is required by the US Food and Drug Administration to ensure that the generic product has equivalent local delivery, equivalent systemic exposure, and equivalent in vitro performance, together ...

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Validating Whole-Airway CFD Predictions of DPI Aerosol Deposition at Multiple Flow Rates | Journal of Aerosol Medicine and Pulmonary Drug Delivery

2016

The objective of this study was to compare aerosol deposition predictions of a new whole-airway CFD model with available in vivo data for a dry powder inhaler (DPI) considered across multiple inhalation waveforms, which affect both the particle size distribution (PSD) and particle deposition...

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Absorption and clearance of pharmaceutical aerosols in the human nose: effects of nasal spray suspension particle size and properties | Pharmaceutical Research

2016

The objective of this study was to use a recently developed nasal dissolution, absorption, and clearance (DAC) model to evaluate the extent to which suspended drug particle size influences nasal epithelial drug absorption for a spray product...

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In vitro tests for aerosol deposition. IV: Simulating variations in human breath profiles for realistic DPI testing | Journal of Aerosol Medicine and Pulmonary Drug Delivery

2016

The amount of drug aerosol from an inhaler that can pass through an in vitro model of the mouth and throat (MT) during a realistic breath or inhalation flow rate vs. time profile (IP) is designated the total lung dose in vitro, or TLDin vitro. This article describes a clinical study that enabled us to recommend a general method of selecting IPs for use with powder inhalers of known airflow resistance (R) provided subjects followed written instructions either alone or in combination with formal training...

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Current Inhalers Deliver Very Small Doses to the Lower Tracheobronchial Airways: Assessment of Healthy and Constricted Lungs | Journal of Pharmaceutical Sciences

2016

To evaluate the regional delivery of conventional aerosol medications, a new whole-lung computational fluid dynamics modeling approach was applied for metered dose inhaler (MDI) and dry powder inhaler (DPI) aerosols delivered to healthy and constricted airways. The computational fluid dynamics approach included complete airways through the third respiratory bifurcation (B3) and applied the new stochastic individual pathway modeling technique beyond B3 through the remainder of the conducting airways together with a ...

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