Michael Hindle1, P Worth Longest. 1. Departments of Pharmaceutics, Virginia Commonwealth University, Richmond, VA, USA. mhindle@vcu.edu
Abstract
OBJECTIVES: The objective of this study was to investigate the in-vitro particle-size growth of combination drug and excipient submicrometer aerosols generated from a series of formulations and two aerosol delivery devices. METHODS: Submicrometer combination drug and excipient particles were generated experimentally using both the capillary aerosol generator and the Respimat inhaler. Budesonide and albuterol sulfate were used as model drugs and were formulated with sodium chloride, citric acid and mannitol as excipients in various ratios. Aerosol growth was evaluated in-vitro in a coiled-tube geometry designed to provide residence times and thermodynamic conditions consistent with the airways. KEY FINDINGS: Submicrometer combination drug : excipient aerosols when exposed to simulated respiratory conditions increased to micrometer size suitable for pulmonary deposition. It was possible to control the aerosol growth ratio by altering: (1) the hygroscopic excipient, (2) the drug : excipient ratio and (3) the drug. The applicability of this approach was demonstrated using the capillary aerosol generator and the Respimat inhaler. CONCLUSIONS: The enhanced excipient growth approach may enable the delivery of submicrometer aerosol particles that increase in size within the airways and result in high percentages of pulmonary deposition.
OBJECTIVES: The objective of this study was to investigate the in-vitro particle-size growth of combination drug and excipient submicrometer aerosols generated from a series of formulations and two aerosol delivery devices. METHODS: Submicrometer combination drug and excipient particles were generated experimentally using both the capillary aerosol generator and the Respimat inhaler. Budesonide and albuterol sulfate were used as model drugs and were formulated with sodium chloride, citric acid and mannitol as excipients in various ratios. Aerosol growth was evaluated in-vitro in a coiled-tube geometry designed to provide residence times and thermodynamic conditions consistent with the airways. KEY FINDINGS: Submicrometer combination drug : excipient aerosols when exposed to simulated respiratory conditions increased to micrometer size suitable for pulmonary deposition. It was possible to control the aerosol growth ratio by altering: (1) the hygroscopic excipient, (2) the drug : excipient ratio and (3) the drug. The applicability of this approach was demonstrated using the capillary aerosol generator and the Respimat inhaler. CONCLUSIONS: The enhanced excipient growth approach may enable the delivery of submicrometer aerosol particles that increase in size within the airways and result in high percentages of pulmonary deposition.
Authors: A K Kamada; S J Szefler; R J Martin; H A Boushey; V M Chinchilli; J M Drazen; J E Fish; E Israel; S C Lazarus; R F Lemanske Journal: Am J Respir Crit Care Med Date: 1996-06 Impact factor: 21.405
Authors: Benjamin M Spence; Worth Longest; Xiangyin Wei; Sneha Dhapare; Michael Hindle Journal: J Aerosol Med Pulm Drug Deliv Date: 2019-03-11 Impact factor: 2.849
Authors: Guihong Chai; Amr Hassan; Tuo Meng; Lihua Lou; Jonathan Ma; Russell Simmers; Lei Zhou; Bruce K Rubin; Qi Tony Zhou; P Worth Longest; Michael Hindle; Qingguo Xu Journal: Nanomedicine Date: 2020-07-03 Impact factor: 5.307