Journal Article

Good Things in Small Packages: an Innovative Delivery Approach for Inhaled Insulin

Patton, John S., Brandão, Simone Cristina Soares, de Andrade, Armèle Dornelas, de Melo Barcelar, Jacqueline, Molloy, Lisa, Galindo-Filho, Valdecir Castor, Alcoforado, Luciana, Fink, James B.

2017

Overview

Purpose The design development of a small, hand held, battery operated, breath actuated inhaler as a drug/device platform for inhaled insulin posed a number of technical challenges. Our goal was to optimize lung deposition and distribution with aerosol generators producing 3–6 μm particle size distribution. Methods In silico modeling with computational fluid dynamics (CFD) and in vitro testing of device components were assessed using an Alberta idealized adult airway (Copley, UK) to optimize mouthpiece and aerosol path design for dose delivered distal to the trachea. Human factors use testing was designed to determine the ability to perform inspiratory manuevers with LED guidance within target flow limits. In vivo testing with healthy normal subjects of radiolabeled aerosol compared 2 breathing patterns for lung deposition efficiency, distribution, and subject preference. Results CFD demonstrated that flows ≤5 L/min and ≥15 L/min reduced the delivery efficiencg. Prototypes tested with inspiratory flow of 10 L/min provided up to 70% of dose delivered distal to the model throat with aerosols of 3 to 6 μm. Users guided by LED were able to inhale for 8–24 s with 5 s breath hold. Lung dose >70% with peripheral to central ratios >2.0 were achieved, with subject preference for the longer inspiratory time with breath hold. Conclusion The device design phase integration led to a novel design and inspiratory pattern with greater levels of peripheral deposition than previously reported with commercial inhalers. The rationale and process of the application of these methods are described with implications for use in future device development.

• Publisher: Springer US,Springer,Springer Nature B.V
• Subject: Administration, Inhalation / Adult / Aerosols / Aerosols - administration & dosage / Aerosols - chemistry / Aerosols - pharmacokinetics / Aged / Batteries / Biochemistry / Biomedical and Life Sciences / Biomedical Engineering and Bioengineering / Biomedicine / Computer applications / Computer Simulation / Cross-Over Studies / Equipment Design / Female / Humans / Hydrodynamics / Hypoglycemic Agents - administration & dosage / Hypoglycemic Agents - chemistry / Hypoglycemic Agents - pharmacokinetics / Insulin / Insulin - administration & dosage / Insulin - chemistry / Insulin - pharmacokinetics / Light-emitting diodes / Lung - metabolism / Lungs / Male / Medical Law / Middle Aged / Nebulizers and Vaporizers / Particle Size / Pharmacology/Toxicology / Pharmacy / Pharynx / Research Paper / Respiration / Respiratory tract / Size distribution / Trachea / Young Adult