A new method to evaluate plume characteristics of hydrofluoroalkane and chlorofluorocarbon metered dose inhalers

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Abstract

Two concerns raised when comparing metered dose inhalers (MDIs) to other inhalation devices are their relatively high throat deposition and the ‘cold-Freon’ effect seen in a small number of patients. The cold-Freon effect is presumed to be a result of the cold, forceful MDI plume impacting on the back of a patient’s throat. This in vitro study uses a new plume characterization method to determine the spray force and plume temperature of various MDIs. Spray force measurements were made for 28 marketed products consisting of bronchodilators, steroids, press-and-breathe, breath-actuated and nasal inhalers. Results show that chlorofluorocarbon (CFC)-containing MDIs produce extremely forceful and cold plumes. Several hydrofluoralkane (HFA)-containing MDIs produced much softer and warmer plumes, but two HFA products had spray forces similar to the CFC products. Although the type of propellant used can affect spray force, actuator orifice diameter is the most important factor. Data obtained from marketed products and experimental inhalers show that MDIs that have a low spray force also have low throat deposition.

Introduction

Metered dose inhalers (MDIs) have long been a reliable and inexpensive medication delivery form for the treatment of asthma. Two concerns raised when comparing MDIs to other inhalation devices are their relatively high throat deposition (Newman et al., 1981) and the cold-Freon effect seen in a small number of patients (Crompton, 1982, Pedersen et al., 1986). The cold-Freon effect is a result of a forceful blast of cold, liquid propellant impacting on the back of the patient’s throat. In addition to being uncomfortable for the user, this can result in an inconsistent or non-existent dose delivered to the lung. Both adverse conditions, high throat deposition and the cold-Freon effect, share a common cause: a high-velocity, forceful blast of formulation exiting the device. The forceful plume can be especially uncomfortable when using nasal devices.

With the redesign of MDIs to contain hydrofluoroalkane (HFA) propellants instead of the ozone-depleting chlorofluorocarbons (CFCs), system improvements have resulted in MDIs with much lower throat deposition (Leach et al., 1996) and qualitatively different plume characteristics, such as reduced plume force (Purewal et al., 1998).

In this paper, a new method of quantifying the force and temperature of MDI plumes is described. These measurements provide an in vitro method for determining whether an MDI exhibits the plume characteristics associated with the cold-Freon effect and high throat deposition. Several marketed products were tested, including bronchodilators, steroids, press-and-breathe, breath-actuated and nasal MDIs. Spray force measurements are shown to be a good indicator of the amount of drug deposition occurring in the throat. The effects of some MDI design changes on plume dynamics are also discussed.

Section snippets

Description of the data acquisition system

A test apparatus was developed (Fig. 1) to measure the impact force, duration and temperature of an MDI plume as would be sensed by a patient. The MDI was actuated such that the plume would strike the center of a 4.5-cm square plate (0.5 g) located 5 cm from the end of the MDI mouthpiece. A customized data acquisition system (Power Macintosh 8100/80 with NB-MIO-16L DAQ board; National Instruments, Austin, TX) captured the output from a precision miniature load cell (Model 34; Sensotec,

Evaluation of marketed products

The results show that all of the CFC products tested have forceful plumes, with forces ranging from 80 to 117 mN (Table 1). The nasal devices span an even larger range, 55–179 mN. The impact force, temperature and spray duration measurements of the steroid press-and-breathe MDIs are shown in Fig. 2. The results are shown in the form of box plots. Box plots are useful for showing the entire distribution of the data. A line is drawn across each box at the median. The bottom of the box represents

Conclusions

A new method of quantifying the force and temperature of MDI plumes has been described. This method provides an in vitro technique for determining whether an MDI exhibits the plume characteristics associated with the cold-Freon effect and high throat deposition.

Spray force and plume temperature measurements were made on marketed bronchodilators, steroids, press-and-breathe, breath-actuated and nasal MDIs. CFC and HFA products were tested. Spray force measurements ranged from 29 to 179 mN among

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