Dosage forms pulmonary drug delivery

As it becomes increasingly probable that delivery of drugs as aerosols can be achieved readily, the focus can shift to the nature of the therapeutic agent and its physical and chemical stability in the required dosage forms. New chemical entities can be considered for delivery to the lungs to facilitate the control of pulmonary diseases or diseases that may be treated by pulmonary drug delivery. 

Taylor, K. (2002) Pulmonary drug delivery, in Aulton, M. E. (ed.), Pharmaceutics, the Science of Dosage Form Design (). Churchill Livingston, Edinburgh, 473 98. 

Protein-based drugs have been formulated mainly as stable liquids or in cases where liquid stability is limiting as lyophilized dosage forms to be reconstituted with a suitable diluent prior to injection. This is because their delivery has been limited primarily to the parenteral routes of intravenous (IV), subcutaneous (SC), or intramuscular (IM) administration. There are a few drugs that have been developed for pulmonary delivery, such as rhDNase (Pulmozyme ) and an inhalable formulation of insulin (e.g., Exubra ). However, even such drugs have been formulated as either liquid or lyophilized or spray-dried powders. This chapter will focus only on excipients that are applicable to liquid and lyophilized protein formulations. 

Inhalation aerosols have been used for the delivery of drugs to the respiratory system since the mid-1950s. The most common dosage form for inhalation is the metered-dose inhaler (MDI), by which the drug is delivered from a pressurized container using a liquefied gas propellant. Medication delivered via this dosage form has allowed for a quick therapeutic response to the symptoms of asthma, emphysema, and chronic obstructive pulmonary disease (COPD), and has resulted in an improvement in the quality of life for millions of asthma sufferers. 

Another issue is reproducibility. The formulation may work perfectly in an in vitro test system, but the dosage form requires aerosolization, and lung deposition is a function of the characteristics of the aerosol (dose, mass concentration, droplet/particle size, etc.) and the nature of the inspiratory maneuver, a factor that the patient has control over. These factors can influence performance to a far greater extent than can be built into a particle, and thus the term controlled does not seem a defensible objective for pulmonary delivery. The vagaries of the deposition profile and of the amount that will deposit also imply that sustaining a certain drug concentration is a difficult proposition, but the loosest definition extended release, seems an acceptable goal within the boundaries set by the clearance mechanisms. 

Apart from oral drug delivery, the drug nanoparticles might have a large potential in pulmonary delivery but also in parenteral dosage forms, in particular, the fad that some nanosuspensions may behave like solutions regarding their pharmacokinetics (3) appears to be a very interesting feature. 

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