Download Development of novel pressurised metered dose inhaler (pMDI

Supervisor: Dr Peter Seville
Email: [email protected]
Development of novel pressurised metered dose inhaler (pMDI) systems for pulmonary
delivery of proteins and peptides
The aim of this research is to investigate the use of spray-drying protein and peptide
macromolecules in the presence of selected surfactants to prepare stable and respirable HFA
pMDI suspension systems for pulmonary administration.
Traditionally, drugs are delivered to the lung to treat conditions of the airways. These include
drugs to control the symptoms of asthma, such as “reliever” and steroid medications. Aside
from conventional drugs, pulmonary drug delivery could also potentially be used for the
delivery of macromolecules. These compounds are extremely sensitive to the harsh
environment in the stomach, and administration by mouth (e.g. in tablet form) leads to rapid
degradation of the drug. In contrast, inhalation of these macromolecules potentially allows
increased levels of the drug to be absorbed by the body. An example of such a
macromolecule that has been studied extensively is insulin, used in the treatment of diabetes.
However, there are a number of disadvantages to be overcome when using the inhalation
route to deliver drugs to the general circulation. The lungs are relatively inaccessible, and
complex devices are required to deliver the drug to the appropriate area of the lung. The
epithelial surface of the airways is covered by a mucus layer; a drug delivered to the lung may
become trapped within this mucus, and subsequently removed from the lungs before the drug
can be absorbed, through a process known as mucociliary clearance. In addition, the lung
has a number of enzyme systems present that may degrade the drug, and also has migrating
macrophages, which have the ability to engulf particles.
This project aims to address some of these limitations in the delivery of macromolecule drugs
to the lung, using an innovative method to formulate aerosol-based pressurised metered dose
inhaler (pMDI) systems. The project will use spray-drying to produce novel dry powders,
incorporating excipients during the spray-drying process to ensure stability and increase the
dispersibility of the powders during inhalation. Following full characterisation, these powders
will be formulated as pMDI systems. The delivery of drug from the inhaler will be evaluated
using in vitro models of pulmonary drug delivery deposition.
The objectives of the work are clearly defined, as follows:
1. To spray-dry protein and peptide macromolecules in the presence of thermoprotectant
agents to determine the optimum spray-drying parameters.
2. To determine the effect of the addition of surface-active agents on the dispersibility of the
spray-dried product.
3. To extensively characterise the physico-chemical characteristics of the spray-dried
product with respect to moisture content, particle size distribution, morphology, and
macromolecule loading and integrity.
4. To formulate pMDI systems using surfactant-modified powders to generate stable and
dispersible suspension formulations.
5. To quantify the respirable fraction of optimised formulations following aerosolisation, and
to determine the pulmonary deposition and bioavailability of the macromolecule using an
in vitro simulated lung model.