chitosan and plga microspheres as drug delivery ... - UniCA Eprints

201. General Introductionliquid (84). The droplets at the nebulizer outlet become smaller with increasing air velocityand increasing ratio of the mass flow rate of air to liquid. Increasing the nebulizer flow rateincreases the aerosol output rate (78). The formation of droplets depends on the properalignment and placement of the jet nozzle, liquid inlet, and impaction surface; manynebulizers have baffles to remove larger particles by impaction. Thus, the internal orientationand geometry of the jet nebulizer is critical to maintaining a reproducible output and sizedistribution. The output and size distribution are also affected by droplets' impacting andsettling onto the tubing downstream of the nebulizer (79). Other factors that in somesituations affect the droplet size are the gas density and the liquid surface tension andviscosity (84). The solution concentration itself has no effect on the size distribution of thedroplets except to the extent that it changes the physical characteristics of the solution (78,80). The nebulizing action causes continual reflux of a large volume (and surface area) ofwater, which promotes extensive water evaporation. Evaporative losses from the solution canbe decreased by using air from a compressor, which supplies air at ambient humidity, ratherthan from a compressed gas cylinder, which supplies air that is totally dry. In summary, thesize and solute concentration of droplets are affected by any difference in vapor pressurebetween the droplet and the surrounding air and the time available for equilibration. Thusgradients of relative humidity and temperature do affect the droplets and can cause the soluteconcentration in the droplets to be different from that of the nebulized fluid (80, 85).1.4.2. Mechanism of Drug DepositionDrugs for inhalation therapy are administered in aerosol form. The ability of the aerosolizeddrug to reach the peripheral airways is a prerequisite for efficacy. The regional pattern ofdeposition efficiency determines the specific pathways and rate at which deposited particlesare ultimately cleared and redistributed (86). The pathology of disease of the lungs mayconsiderably affect aerosol deposition. Patients with airway obstruction (eg, emphysema,asthma, chronic bronchitis) who inhaled radiolabeled aerosol showed increased central(tracheobronchial) deposition and diminished penetration to the peripheral pulmonary regions(87). The mechanisms by which particles deposit in the respiratory tract include impaction(inertial deposition), sedimentation (gravitational deposition), brownian diffusion,interception, and electrostatic precipitation (86, 88, 89). The relative contribution of eachdepends on the characteristics of the inhaled particles, as well as on breathing patterns andrespiratory tract anatomy. All mechanisms act simultaneously, but the first two mechanismsare most important for large-particle deposition within the airways (1 mm , MMAD , 10 mm).