LYN S DAINTREE1*, PETER YORK2,3
*Corresponding author
1. Development Director, Crystec Ltd, Bradford, United Kingdom
2. Chief Scientist, Crystec Ltd, Bradford, United Kingdom
3. Emeritus Professor, Faculty of Life Sciences, University of Bradford, Bradford, United Kingdom

Abstract

Aerosol dispersion and deposition performance from dry powder inhalers are dependent on drug particle aerodynamic diameter and size distribution, formulation composition (including surface modification and bulking agents), inhaler device and patient operation. This review will focus on ‘bottom-up’ particle engineering technologies for providing drug delivery by dry powder inhalation. By ‘designing-in’ performance of drug particles and/or drug composite systems, emerging commercial ‘bottom-up’ particle formation technologies allow for the generation of powders that exhibit good aerodynamic performance, excellent inter- and intra-batch variability with less dependence on the delivery device, as well as enhanced physical and chemical stability. There is an opportunity to obtain co-deposition of drug and carrier materials, surface acting agents and / or multiple drugs at the same site of dissolution / absorption that can lead to an improved clinical outcome for both local and systemic delivery.

INTRODUCTION
Aerosol dispersion and deposition performance of Dry Powder Inhalers (DPIs) are dependent on the Mass Median Aerodynamic Diameter (MMAD) and Geometric Standard Deviation (GSD) of drug particles, formulation composition and associated excipient particle characteristics, as well as the inhaler device and its operation by the patient. This article will focus on ‘bottom-up’ technologies where the drug is dissolved in a suitable solute and particles are formed by drying the drug solution using a single-step process. Drug particles between 5 and 10 µm will generally be deposited in the upper airways, 0.5-5 µm will sediment in the deep lung, whilst those of <0.5 µm will undergo Brownian motion and are likely to be exhaled by patients. The larger the GSD, the more sites that the aerosol will deposit in the respiratory tract. Ideally aerosols should have a GSD of <2 and be as close to monodispersity as possible to increase deposition at the desired site of action, in turn increasing efficacy of the treatment (1). Often the drug is highly potent and with the limitation of powder filling equipment and the propensity of particles with a geo ...