Problems with inhalational drug delivery

Inhalational therapy is used to deliver medication to the lung, either to treat diseases or, less commonly, for systemic absorption. A number of devices have been developed to aid or improve inhalational therapy, and this thesis deals with metered dose inhalers, used with spacer devices, and nebulisers. Despite their seemingly simple construction and concept, the correct choice and use of an inhalational drug delivery device can dramatically alter the amount of drug available for inhalation. Studies in this thesis, supported by emerging pharmacokinetic evidence, have highlighted areas where the device can affect the drug delivery. In vitro methods were used to quantify and characterise the different devices, including inertial impaction for aerosol particle sizing, sinus flow pumps for breathing simulation and high speed video recordings to analyse aerosol plume geometry and spacer function. The results these studies reveal a number of factors that may affect drug delivery. Firstly, delay between metered dose inhaler actuation into a spacer and inhalation can reduce the amount of drug available to the patient. Secondly, multiple actuations of the metered dose inhaler into the spacer prior to inhalation also reduce the amount of drug available. The size of the spacer may also affect the amount of drug available for inhalation, and this will vary with the drug prescribed. Different formulations may differ in their aerosol cloud speed and volume, and this may alter the amount of drug delivered from different spacers. Plastic and polycarbonate spacers may be highly charged with static electricity. Such spacers deliver less drug than those where the static charge has been reduced by an anti-static lining, or where the spacer is constructed from static dissipative materials. Washing the spacer also reduces its charge, but the optimum washing regime for spacers is not known. Different nebulisers deliver different amounts of drug, and the assessment of nebulisers varies with the method used. Accurate assessment should include direct measurement of the mass of drug released, and should incorporate simulated patient breathing. Effective nebulisation of drug ends after a few minutes. This time will depend on the nebuliser and drug being used, but for some medications administered for asthma, little drug may be delivered after five minutes, and patients should be advised to stop nebulisation after this time. In conclusion, studies in this thesis support the hypothesis that the method of use or choice of inhalational drug delivery device affects the amount of drug that is available for inhalation by the patient.