Drugs for treating respiratory and nasal disorders are frequently administered in aerosol formulations through the mouth or nose by using metered dose inhalers. Patients often rely on medication delivered by this system for rapid treatment of respiratory disorders which are debilitating and, in some cases, even life threatening. Therefore, it is essential that the prescribed dose of aerosol medication delivered to the patient consistently. Thus, testing of metered dose inhaler units for proper drug delivery by the metering dose valve is a part of the manufacturer's quality assurance procedure.
One conventional method to test delivery of metered dose inhalers consists of taring each metered dose inhaler and measuring the weight lost after the delivery of one dose. This method is accurate and adequate for testing a small number of samples. However, it slows down the process for a high-speed production and packaging of metered dose inhalers.
Another common method of testing drug delivery utilizes indirect pressure decay after activation of each metered dose inhaler. This method does not render a direct mass measurement, but rather an approximation based upon the force exerted indirectly by the superheated vapor on a pressure transducer. As a consequence, this method is unable to detect those metered dose inhalers marginally out of tolerance.
A newer method developed by Glaxo Inc. researchers (US Patent 5,261,538) comprises passing the mass over a heat loss measuring device, calculating the amount of heat loss accompanying the vaporization of the mass and correlating the heat loss to measurement of heat loss of known liquid aerosol mass made with the same device.
When a liquid is released from a sealed container, the liquid extracts heat from its environment, e.g., the surrounding air, to evaporate. The extraction of heat from the liquid's surrounding results in a lowering of the temperature of those surroundings. When a volatile liquid, e.g. propellant 12 with boiling point - 29.8 degree C, is released into the air as a fine spray at ambient temperature, the evaporation is very rapid and the consequential cooling of the air is observable even to the touch. When the valve of a propelled aerosol dispenser is activated, the released propellant very rapidly evaporates to produce the aerosol, i.e., a fine suspension of the aerosol formulation in air and vaporized propellant. The rapid evaporation of the propellant extracts heat from the surrounding air producing a significant cooling effect.
Thus, Glaxo researchers measured a mass of a volatile liquid by discharging that volatile liquid into a constant temperature and constant flow air stream and onto the probe of a heat loss measuring device placed downstream from the point of discharge. The instrument sensed the cooling effect of the vaporization of the liquid as a transient loss of heat from the area surrounding the probe and recorded as a transient reduction of temperature of the air stream. The researchers repeated the procedure with two or more different, known masses of the same liquid (as a standard for comparison). Thus, they determined the mass of the sample by correlating the reduction in temperature resulting from its discharge with reduction in temperature caused by discharge of the samples of known mass.