Asthma aerosol delivery systems

Varner A, Busse W 1996 Are you undertreating inflammation in asthma Journal of Respiratory Disease 17 656-668 Viel L 1999 Therapeutic efficacy of inhaled fluticasone propionate in horses with chronic obstructive pulmonary disease. In Proceedings of the 45th American Association of Equine Practitioners Annual Convention, Albuquerque, NM, pp. 306-307 Votion D, Ghafir Y, Munsters K et al 1997 Aerosol deposition in equine lungs following ultrasonic nebulisation versus jet aerosol delivery system. 

The use of aerosol delivery systems continues to be a desirable means of administering locally acting agents to the lungs. Since the early 1990s there has been a surge of interest in the pulmonary delivery of proteins and peptides for systemic activity but to date none of these products have made it to market [1], During this period the major commercial successes have been in the form of dry powder systems [2] and alternative propellant systems [1], as will be discussed later in the chapter. The incidence of asthma and chronic obstructive disease continues to rise and the need for improvement and diversity of therapies remains a priority in their treatment [3]. 

P2"Agonists are widely used in the symptomatic treatment of asthma. Although both oral and aerosol formulations of these bronchodilators have been available for many years, advances have occurred in deUvery technology with the development of dry powder aerosols (qv) (see Drug delivery systems) (28). The ease of usage of these breath-activated systems has improved patient compliance and therapeutic response. There are several detailed reviews on p2-agonist therapy of bronchial asthma (29—31), and on the stmcture-activity relationships of this class of drugs (32). 

The first purified and characterized drug substances were administered as aerosols as a topical treatment for asthma approximately 50 years ago. More recently, drugs have been evaluated for systemic delivery. For each category of drug the mechanism of clearance from the airways must be considered. These mechanisms may be listed as mucociliary transport, absorption, and cell-mediated translocation. The composition and residence time of the particle will influence the mechanism of clearance. 

Inhalation aerosols have been used for the delivery of drugs to the respiratory system since the mid-1950s. The most common dosage form for inhalation is the metered-dose inhaler (MDI), by which the drug is delivered from a pressurized container using a liquefied gas propellant. Medication delivered via this dosage form has allowed for a quick therapeutic response to the symptoms of asthma, emphysema, and chronic obstructive pulmonary disease (COPD), and has resulted in an improvement in the quality of life for millions of asthma sufferers. 

Inhalation Inhalation provides the rapid delivery of a drug across the large surface area of the mucous membranes of the respiratory tract and pulmonary epithelium, producing an effect almost as rapidly as by intravenous injection. This route of administration is used for drugs that are gases (for example, some anesthetics), or those that can be dispersed in an aerosol. The route is particularly effective and convenient for patients with respiratory complaints (for example, asthma or chronic obstructive pulmonary disease) as drug is delivered directly to the site of action and systemic side effects are minimized (see p. 219). 

The metered-dose aerosol inhaler is not only a most convenient system for the delivery of therapeutically active drugs but it has proven to be a life-saving device for many asthmatics. This system has made it possible for millions of asthma sufferers to lead normal lives. The convenience of self-administering a dose of drug accurately and quickly has made the metered-dose aerosol the dosage form of choice for the delivery of drugs to the respiratory system. From epinephrine to albuterol, from triamcinolone to flunisolide, from proteins and peptides to hormones, this dosage form has proven its value. 

Steroids, which are active following oral ingestion, such as prednisone, prednisolone, and dexamethasone, cause significant systemic immunosuppression, with consequent risks to the health of the patient. Since the inflammation associated with asthma is localized in the lungs, local topical delivery with aerosols has the... 

In vitro and in vivo studies suggested that aerosolizing E25 would deliver the therapeutic primarily to the ELE with low and limited delivery to the serum. The quantity delivered to lung interstitium could not be determined. To evaluate the potential efficacy of topical delivery to the lung surface and to estimate dose, a suitable animal model would be advantageous. However, no suitable animal model was available. Rodent models of asthma could not be used to evaluate efficacy since E25 does not bind to rodent IgE. Also, although E25 does bind to monkey IgE, at the time of these studies there was no well-characterized monkey model of asthma. We decided that the fastest way to evaluate the efficacy of aerosolized E25 was to use a human bronchoprovocation model of asthma since systemic delivery of E25 was found to be efficacious in this model (21,22). 

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