Pulmonary drug delivery

Published on November 30, 2017   41 min

Other Talks in the Series: Advances in Asthma

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My name is Anthony 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, the characteristic tests that are usually performed with regard to regulatory standards, for example, and submissions, and then I'll conclude here with a few in vivo considerations.
The therapeutic drug category 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 broncoconstriction 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 after being 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, 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- inflammatory, and gluco corticosteroids are given for this purpose which includes fluticasone and bedesonide as some of the more modern steroids. Cystic fibrosis is a genetic disease in which the core line 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 allowing the 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 in to 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 not only entered 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 disease, it's a migraine headache where we use ergotomine or hydroxyergotamine. So the sight of action then is in the brain. And then diabetes which is treating the either type one or type two diabetes, type one being early onset and type two being late onset disease, and where inhaled insulin will treat the glucose in the circulation.