The best magazine
Critical Aspects of pMDI Operation
Storage
The inhaler should be stored at room temperature in the upright position, so that the tip of the canister valve is facing down. Temperature extremes are thought to change the vapor pressure of the propellant and can lead to changes in actuated particle size, flight, and deposition. Storing the canister valve-down helps keep the internal gasket wetted with propellant. If the canister is stored for extended periods in such a way that the gasket is not in contact with the liquid propellant, the gasket can become brittle and fail, potentially resulting in the ingress of moisture. The accumulation of moisture in the canister can affect aerosol formation and propellant evaporation upon actuation. Changes in these factors can affect particle size, flight, and deposition and ultimately decrease the respirable dose.
Gasket failure may also result in the loss of propellant from leakage. Not only can this affect the pressure of the aerosol generated on actuation, it can also result in concentration of the medication and potentially lead to irreversible aggregation or precipitation in the canister.
Shaking
Vigorous shaking of the pMDI before each actuation is of the utmost importance in ensuring reproducible delivery of the optimal respirable dose, with medications formulated as suspensions (all SABAs) being of particular concern. Flocculation—the aggregation of suspended drug particles into woolly clumps—occurs rapidly by design in pMDI canisters containing suspension formulations (Figure 1). These rapidly formed clumps readily disperse into a reasonably homogeneous suspension with vigorous shaking. While such flocculated systems are prone to form less easily dispersed creams over extended periods, formulations that allow for slower aggregation of drug particles are prone to caking. This yields a dense packing of drug that is much more difficult to resuspend. The salient point is that the suspension flocculates fairly quickly and must be redispersed before each actuation. PI instructions for solution-based pMDI formulations differ as to shaking requirements, with two products (Qvar and Alvesco) indicating no need for shaking. As the various SABA and ICS pMDI formulations are not expected to react adversely to shaking, advising patients to shake all pMDIs in the same manner may simplify patient education.
(Enlarge Image)
Figure 1.
Flocculation of various HFA formulations of fluticasone (Flixotide), fluticasone propionate/salmeterol xinafoate (Seretide), and albuterol (Ventolin, Salamol, and Airomir) 30 seconds after shaking.
HFA: hydrofluoroalkane.
Source: Reference 23. Reprinted with permission of Phil A. Jinks.
It is important to recognize that the contents of the pMDI metering chamber do not change substantially during the shaking process. Instead, shaking determines the contents of the next dose, which fills the metering chamber as the canister recoils after actuation. If the pMDI is primed before use (see below), it should be shaken before each priming actuation to ensure that the metering chamber is filled with a homogeneous suspension of medication. If the device is not thoroughly shaken before actuation, drug-free propellant can fill the metering chamber, resulting in an exceedingly low subsequent dose.
Priming
Despite the recommendation to store the pMDI canister valve-down, doing so for relatively short periods (<24 hours) has been shown to result in leakage of suspended drug from the metering chamber back into the canister. Thorough shaking before actuation will not rectify this loss, so the first actuation after prolonged storage can be expected to deliver a significantly diminished dose. To counter the loss of medication to leakage, it is advised that multiple primer actuations be wasted to air before the first dose is administered for inhalation.
As mentioned above, it is necessary to thoroughly shake the device before each actuation, as this will ensure that the metering chamber is consistently filled with an optimal dose of medication. Not only does the duration of disuse requiring priming differ between inhalers, but a given inhaler may need a different number of priming actuations in different situations (Table 1). Also, dropping the inhaler is a specific indication for the priming of some (although not most) products. For some patients, it is anticipated that using a single consistent protocol will lead to better outcomes and that it may be advisable to prime all pMDIs according to the most frequent schedule. Although such a strategy may normalize usage, it will likely lead to unnecessarily wasted medication. Therefore, clear and thorough training on the proper use of each prescribed pMDI is optimal and is the most economical approach for patients.
Exhalation Prior to Actuation
A 2015 study found that "exhaling to functional residual capacity or residual volume" (i.e., normal, comfortable expiration) before actuating the canister was the most commonly missed step in the 93% of patients who failed to properly operate their rescue inhaler. Similarly, a 2002 study rated forced expiration as the most common error among patients misusing their ICS pMDI. Confusion over this step is understandable, considering the variety of instructions patients face pertaining to predose expiration ( Table 1 ). Given that all albuterol rescue inhaler PIs instruct the patient to "breathe out as much as possible" or "as much as you can," it should perhaps come as no surprise that the most common mistake in such studies is the failure to simply exhale normally.
It is unclear why forced expiration was considered an error in the 2002 study, other than that it did not conform to what the authors defined as proper technique. Forced expiration may result in poor control over the initial rate of the dosed inhalation, although the effects on airway deposition are unclear. Perhaps of greater concern is the lack of conscious expiration before dosing, which will prevent the deep inhalation necessary for optimal delivery of medication.
In any event, full exhalation (presumably best defined by the relevant PI) immediately prior to actuation of the device is necessary for optimal drug delivery. Patients should be counseled to completely exhale before bringing the mouthpiece to their lips. A mistimed actuation coupled with exhalation into the mouthpiece will result in deposition of the dose in the actuator or spacer chamber. In addition, the high moisture content of exhaled air can affect the evaporation of the aerosolized propellant, thereby decreasing the extent of drug delivery by increasing both particle size (aggregation) and drug deposition in the actuator/spacer/mouth, even if the patient has fully exhaled before actuating the device.
Actuation
Actuation should occur immediately after the inhaler is shaken. The device must be held in the proper upright orientation with the mouthpiece down, since tilting will lead to deposition of medication on the tongue or roof of the mouth. Multiple doses should not be cumulatively actuated for a single inhalation, but rather inhaled individually in succession according to the manufacturer's instructions, including the recommended wait time between actuations (Table 1). Aggregation resulting in a decreased respirable dose has been shown to occur when multiple doses are actuated into an attached spacer; therefore, use of a spacer does not influence the need for inspiration following each actuation. It has been suggested that rapid successive actuations will lead to excessive cooling of the metering chamber owing to flash boiling of the propellant. This cooling could potentially result in contraction of the metering-chamber volume, thereby restricting the volume of the next loaded dose. In addition, excessive cooling of the propellant in the metering chamber can change the pressure gradient responsible for creating the aerosol plume, thereby decreasing the delivered dose.
Inhalation
Poor coordination of pMDI actuation and inhalation has been repeatedly identified as a considerable problem for asthma control. Patients should be advised, following full expiration, to place the mouthpiece between their lips and begin a slow, deep breath. Inspiration should begin immediately before actuation of the device, and the breath should continue until inspiratory capacity is reached. The majority of patients inhale too rapidly, which results in inertial impaction of drug to the back of the throat. A slow, deep inspiration is required to ensure optimal delivery of medication to the bronchial tree.
Spacers are effective at decreasing oropharyngeal deposition of inhaled medication, yet do not appreciably decrease the delivery of small respirable particles. When a spacer is used, the coordination of actuation and inhalation is less critical, and a brief delay (~1 second) has been shown to allow for inspiration of a full dose. If a spacer is used, it should be made of static-free material or regularly washed (see below) to minimize the buildup of static charge.
Not every PI instructs the patient to hold his or her breath for a specific amount of time. Most state that the breath should be held for 10 seconds, although some simply say "as long as possible." The majority of PIs direct the patient to remove the device from the mouth immediately after actuation, while others are unclear in this regard. Since exhalation into the mouthpiece can humidify the device and potentially interfere with delivery of a second dose, patients should be clearly instructed to remove the device from the mouth before exhaling.
Counting Remaining Doses
A recent study examining pMDI hardware concluded that patients commonly are unable to determine the end of life of their canister. While underestimation leads to wasted drug, overestimation renders unreliable any dose actuated beyond the nominal canister capacity. Techniques such as floating the inhaler in water, shaking the inhaler, or checking to see whether the inhaler still puffs are inaccurate and should not be recommended. Several modern actuators are equipped with built-in dose counters, although not all rescue inhaler PIs specifically state this. Of eight products marketed in the U.S. that were identified as containing repackaged ProAir HFA, only four mention the built-in dose counter in the PI. Since not all inhalers feature a dose counter, the patient's asthma action plan must be carefully evaluated when switching products so as to ensure that the patient can maintain an accurate count of the doses available in the device.
Cleaning
For most pMDIs, regular cleaning is important for proper function. Residual medication can accumulate on the spray orifice after repeated actuations, resulting in direct blockage of the aerosol. Additionally, the processes of aerosol formation and propellant evaporation introduce a static charge to actuated drug particles. Actuators and spacers also develop a static charge in the course of normal use, which significantly decreases the respirable dose because of the pursuant electrostatic attraction between drug and device. Although static-free spacers have been developed, regular cleaning of plastic spacers with household detergent effectively removes static charge and improves drug delivery.Table 1 lists the recommended cleaning procedure for available pMDIs. The canister must not get wet and should be removed during the washing process to prevent ingress of water. In cleaning an actuator or spacer with water, the device should be allowed to dry completely before reassembly. Shaking the actuator after cleaning removes excess water and decreases drying time. If the inhaler is needed before it has dried, it should be actuated twice before use, and the cleaning procedure should be repeated afterward.
Source: ...