Drug-delivery systems aerosol

Aerosols can be generated by three main drug delivery systems nebulizers, pressurized metered dose inhaler (pMDI), and dry powder inhaler (DPI). 

Intimately related to these factors is the design of the device, formulation, and the interface with the patient. Much of the discussion below will focus on the implications of excipients on formulation challenges for inhaled aerosol products. This chapter summarizes excipients for pulmonary formulations from several perspectives (i) excipient selection based on principles of delivery, (ii) physicochemical requirements for excipients, and (iii) specific challenges for formulations faced with aerosol drug delivery systems, including (a) biological aspects, (b) microbiological aspects, (c) analytical issues, and (d) future prospects. 

Ross DL, Gabrio BJ. Advances in metered dose inhaler technology with the development of a chlorofluorocarbon-free drug delivery system. J Aerosol Med 1999 12(3) 151-160. 

Knoch, M., and Keller, M. (2005), The customised electronic nebuliser A new category of liquid aerosol drug delivery systems, Expert Opin. Drug Deliv., 2, 377-390. 

HaloLite, shown in Fig. 11, is a hand-held drug delivery system developed by Medic-Aid (Bognor Regis, United Kingdom). The device, which uses compressed air, consists of a medication chamber, a control unit, and an aerosol generation assembly that is operated by a portable, dedicated compressor. The aerosol is generated based upon conventional nebulization principles. The control unit allows the patient to select a... 

As described in Chapter 3, several SCF techniques are available for the preparation of drug delivery systems. These include rapid expansion of supercritical solutions (RESS), gas antisolvent recrystallization (GAS), supercritical antisolvent recrystallization (SAS), supercritical antisolvent with enhanced mass transfer (SAS-EM), solution-enhanced dispersion by supercritical fluids (SEDS), supercritical fluid nucleation (SFN), precipitation with compressed antisolvent (PCA), and aerosolized supercritical extraction of solvents (ASES). While RESS and SFN involve the expansion of a supercritical fluid solution of a drug to form drug particles, GAS, SAS, SAS-EM, SEDS, PCA, and ASES use a supercritical fluid as an antisolvent to precipitate particles of a drug dissolved in an organic solvent (5). General RESS and GAS processes are further elaborated in Sections 1.1.1 and 1.1.2. 

For inhalation treatment of respiratory diseases, a pharmaceutical DNase I aerosol is on the market. Pulmozyme is a sterile solution for respiratory use at a concentration of 1000 Genentech Units/mL [22]. It contains 1 mg/mL rhDNase, sodium chloride as a tonicity modifier, calcium chloride as a stabilizer, and water for injection. Since deamidation is rapid at high pH and aggregation occurs at low pH, a nearly neutral solution (pH 6.3) is required. It is administered by means of a compressed air-driven nebulizer. Each 2.5-mL single-unit ampule will deliver 2.5 mg of rhDNase to the nebulizer chamber. The efficacy of DNase inhalation therapy largely depends on the aerosol quality and characteristics, which determine the respirable fraction. Significant differences were found between the different aerosol drug-delivery systems [68,81]. 

However, there will always be situations where the introduction of a new excipient is inevitable. The candidate drug, for instance, maybe incompatible with the current range of excipients. Another reason might be the phasing out of existing excipients for safety or environmental concerns, such as chlorofluorocarbons (CFCs) in metered dose aerosols. There may be a need to introduce a new excipient for a novel drug delivery system or to overcome disadvantages with the currently available materials. 

Unlike most other drug delivery systems, those in the respiratory area can have a major influence on physician/patient acceptance. A wide range of devices are available in the three main categories of dry powder inhalers (DPIs) and metered dose inhalers (MDIs), i.e., pressurised aerosols and nebulisers. The preferred type of inhaler varies considerably between countries (e.g., DPIs in Scandinavia and MDIs in the United States), and between patient groups (e.g., nebulisers for paediatrics). 

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). 

In the United States, federal regulation of aerosol doses varies with devices. The metered-dose inhaler (MDI) utilizes a metering valve that is highly regulated and functionally precise. Nebulizers as drug delivery systems are essentially unregulated. 

Smaldone GC. Drug delivery via aerosol systems concept of aerosol inhaled. J Aerosol Med 1991 4 229-235. 

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