Pulmonary drug delivery

Published on November 30, 2017   41 min

Other Talks in the Series: Drug Delivery

Please wait while the transcript is being prepared...
My name is Anthony (Tony) Hickey. I'm a distinguished fellow at Research Triangle Institute and professor emeritus in the Ascherman School of Pharmacy at the University of North Carolina at Chapel Hill, and I'll be talking about pulmonary drug delivery covering the areas of Pulmonary Biology, dosage forms, characterization and then concluding with some summary remarks.
So overall, I would like to talk about the therapeutic targets, lung deposition and clearance, inhaled drug products, which are divided into pressurized metered dose inhalers, dry powder inhalers, and nebulizers. In vitro tests are the characteristic tests, that are usually performed with regard to regulatory standards, for examples and submissions, and then I'll conclude here with a few in vivo considerations.
The therapeutic drug categories that we are treating with inhaled aerosols include those in asthma and Chronic Obstructive Pulmonary Disease, where we're hoping to bronchodilate the patients so, to treat the symptom of bronchoconstriction or to treat the underlying inflammation. In order to do that, we need to deliver a variety of drugs, some to target the sympathetic nervous system and others to target the parasympathetic nervous system. So, those targeting the sympathetic nervous system are adrenergic agonists and we use a range of Beta 2 adrenergic agonists which are specific to lung tissue and cause bronchodilation. So, short acting beta agonist, as the name suggests, acts generally for a period of four to six hours and have to be given multiple times a day, whereas long-acting beta agonists are given twice a day and act consequently for longer periods of time. There are two examples given here of albuterol as a short-acting beta agonist, and formoterol as a long acting beta agonist. The parasympathetic pathway is treated with muscarinic antagonists, which is to say, anticholinergic agents. And again, we have short-acting Muscarinic antagonists, ipratropium is an example, and long-acting muscarinic antagonist, like tiotropium. The underlying cause of asthma of Chronic Obstructive Pulmonary Disease are inflammatory diseases of course, and so, you have to treat these with anti-inflammatories, and gluco corticosteroids are given for this purpose, which includes fluticasone and budesonide, which are some of the more modern steroids. Cystic fibrosis is a genetic disease in which the chloride ion disposition in the lung is affected, and consequently the patient ends up with a dry lung, inability to move, thick mucus and infections. And so, we have to treat cystic fibrosis patients with aerosols of mucolytics, such as, saline and acetyl choline, which are going to thin the mucus and allow mucus to be cleared. Leukocyte DNAse, which basically chops up the DNA that is in the lung from the incursion of inflammatory cells, which are treating or coming into actually take care of the infection. And then antimicrobial agents, such tobramycin, which are treating the infection that you see in cystic fibrosis, which is largely pseudomonas aeruginosa. There are other diseases that we attempt to treat, such as these systemic diseases, where the drug has to not only enter the lungs, but then is absorbed and acts systemically. And one of the older diseases or older drugs for which we need to treat the diseases, are for migraine headaches, where we use ergotamine or hydroxyergotamine. So, the site of action then is, in the brain. And then diabetes which is treating the, either type 1 or type 2 diabetes, type 1 being early onset and type 2 being late onset disease, and where inhaled insulin would treat the glucose in the circulation.