Metered-dose inhaler surfactants

Baeckstroem K, Nilsson PG. Measurements of droplet size distributions from metered dose inhalers with different vapor pressures and contents of surfactant. J Aerosol Sci 1988 19(7) 1097-1100. 

Metered dose inhaler has been the most popular aerosol delivery device for the treatment of respiratory diseases, which is attributable to its portability and simple operation. Although seemingly easy to use, the MDI is a sophisticated device in design. The drug(s) are suspended or dissolved in a liquefied propellant system, which may also contain excipients such as cosolvents or surfactants. The formulation is kept pressurized in a small canister, sealed with a metering valve. Upon actuation through an actuator, the valve opens and the metered dose is dispensed as an aerosol spray from the expansion and vaporization of the propellant under ambient pressure. The inhalers may be used alone or with spacer devices, the electrostatic issues of which are considered in a later section. The present discussion focuses on the inherent charging of particles produced from MDIs. 

As a consequence of the suppression or reduced use of CFC propellants, a new kind of dosage form is under worldwide development drug powder inhalers (DPIs). The metered dose inhalers (MDIs) will probably be replaced by these. The MDIs were formulated several years ago. A drug in powder form (with a particle size close to 5 pm) was suspended in propellant 11 with a surfactant. Propellant 12 was added to the can after closure. 

Surfactants are found in both solution and suspension formulations of metered dose inhalers (MDIs). The most common surfactants found in pressurised aerosol preparations include sorbitan trioleate (Span 85),... 

Clarke, J.G. Wicks, S.R. Earr, S.J. Surfactant mediated 42. effects in pressurized metered dose inhalers formulated as suspensions. I. Drug/surfactant interactions in a model propellant systems. Int. J. Pharm. 1993, 93, 221-231. 

Tetrafluoroethane is a hydrofluorocarbon (HFC) or hydro-fluoroalkane (HFA) aerosol propellant (contains hydrogen, fluorine, and carbon) as contrasted to a CFC (chlorine, fluorine, and carbon). The lack of chlorine in the molecule and the presence of hydrogen reduces the ozone depletion activity to practically zero. Hence tetrafluoroethane can be considered as an alternative to CFCs in the formulation of metered-dose inhalers (MDIs). It has replaced CFC-12 as a refrigerant since it has essentially the same vapor pressure. Its very low Kauri-butanol value and solubility parameter indicate that it is not a good solvent for the commonly used surfactants for MDIs. Sorbitan trioleate, sorbitan sesquioleate, oleic acid, and soya lecithin show limited solubility in tetrafluoroethane and the amount of surfactant that actually dissolves may not be sufficient to keep a drug readily dispersed. 

The adsorption or incorporation of molecules, such as surfactants and polymers, can create a steric repulsion that prevents aggregation [288-290]. This can also increase suspension stability, important for metered-dose inhaler formulations [291]. Lung surfactant coating on the surface of poly(lactic-co-glycolic) acid microparticles has been shown to dramatically improve dry powder aerosol performance by reducing particle-particle interactions [134,292],... 

Co-solvents in metered dose inhalers were commonly used in CFG formulations to aid in drug solubilization. In HFA formulations, co-solvents continue this same function, but have additional benefits in the new systems, such as solubilization of other excipients. Vervaet and Byron discuss water solubility in the various propellants addressed here, where the addition of ethanol to the HFA system considerably increases the solubility of water (Vervaet and Byron, 1999). Likewise, ethanol was found to increase the solubility of several surfactants in HFA (Vervaet and Byron, 1999 Stein and Stefely, 2003). Suspension formulations using this technique (surfactant plus ethanol) must be made with caution however, as ethanol can also increase the solubility of the drug substance, potentially causing increased particle growth via Ostwald ripening. Nonetheless,... 

Although chronic theophylline administration has been used extensively in the past, this therapy is being employed with decreasing frequency in favor of aerosolized /32-receptor agonists. Albuterol is used most commonly, one to two puffs of the metered-dose inhaler three to four times daily. The role of aerosolized surfactant also has been assessed in patients with stable chronic bronchitis and has demonstrated encouraging results with respect to improvement in pulmonary function and sputum transport by cilia (i.e., clearance). The role of surfactant as a carrier vehicle for other aerosol medications also appears promising and most likely will continue to be evaluated. 

Fedina, L. T., R. Zelko, L. I. Fedina, Z. S. Szabados, M. Szanto, and G. Vakulya. 1997. The effect of surfactant and suspending agent concentration on the effective particle size of metered-dose inhalers. /. Pharm. Pharmacol. 49 1175-1177. 

Clarke JG, Farr SJ, Wicks SR. Technetium-99m labelling of suspension type pressurised metered dose inhalers comprising various drug/surfactant combinations. Int J Pharm 1992 80 R1-R5. 

Uses W/o emulsifier, wetting agent, pigment dispersant for cosmetics, pharmaceuticals (oral, topical, parenteral), food/food pkg., paints, inks, metalworldng fluids, adhesives, industrial applies. surfactant for nasal dosage and metered dose inhalers emulsifier for intramuscular pharmaceuticals food-pkg. adhesives, coatings defoamer in food-contact paper/paperboard emulsifier in m. of food-con-t3ct srticiss... 

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