Pulmonary drug delivery oral bioavailability

The pharmacokinetic/dynamic parameters involved in pulmonary drug delivery of glucocorticoids have been reviewed. Among these, low oral bioavailability, high pulmonary deposition, pronounced clearance, and sustained pulmonary release are the most important parameters to be considered. 

The lack of activity after oral administration for most peptides and proteins resulted in the past besides parenteral application into the utilization of nonoral administration pathways, for example, nasal, buccal, rectal, vaginal, percutaneous, ocular, or pulmonary drug delivery [27]. Drug delivery via these administration routes, however, is also frequently accompanied by presystemic degradation processes. Bioavailability of numerous peptides and proteins is, for example, markedly reduced after subcutaneous or intramuscular administration compared to their intravenous administration. The pharma-cokinetically derived apparent absorption rate constant is thus the combination of absorption into the systemic circulation and presystemic degradation at the absorption... 

Pulmonary deposition efficiency depends on physicochemical characteristics, such as density of the aerosol or dry powder particles [33-35], Generally, particle diameters less than than 5 pm are required for efficient pulmonary delivery [36, 37], Pulmonary deposition also depends on the nature of the delivery device and differs between metered dose inhalers (MDIs). For example, pulmonary deposition expressed as the ratio of pulmonary versus total (pulmonary + oral) absorbed drug, ranged from 15-55% for a number of salbutamol devices and from 66-85% for drugs with lower oral bioavailabilities such as budesonide. 

Technological advances in both biotechnology and molecular biology have yielded a surge in the number of new chemical entities that are produced to treat specific diseases or ailments. However, a growing portion of these new chemical entities display poor aqueous solubility, leading to poor oral bioavailability and an inability to form intravenous formulations. Nanoparticle formation has been proposed and utilized as a method to improve oral bioavailability of poorly soluble drugs and as a method for delivery of particles via parenteral, pulmonary, and topical administration. 

Application of SCF is now the subject of increasing interest especially in the pharmaceutical industry and there are three aims increasing bioavailability of poorly soluble molecules designing sustained-release formulations and formulation of active agents for new types of drug delivery that are less invasive than parental delivery (oral, pulmonary, transdermal). The most complex challenge is related to therapeutic delivery, as it is extremely difficult to obtain a satisfactory therapeutic delivery effect due to biomolecule instability and very short half-life in vivo. 

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