Nebulizers drug concentration

Table 2 Final drug concentration (mg/ml) in the nebulizer reservoirs...

Changes in drug concentration during nebulization (i.e., potential changes in drug delivered versus time)... 

Ito K, Kikuchi S, Yamada M, Toni S, Yoshida M. Time course of drug concentrations in nebulizers and nebulized solutions. Arerugi 1992 41(7) 772-777 (in Japanese)... 

Continued nebuiization Continued nebulization of acetylcysteine with a dry gas results in concentration of drug in the nebulizer due to evaporation. Extreme concentration may impede nebulization and drug delivery. Dilute with Sterile Water for Injection as concentration occurs. 

Nebulizers are devices for converting aqueous solutions or micronized suspensions of drag into an aerosol for inhalation, although the drug formulations are, wherever possible, aqueous solutions. Selection of appropriate salts and pH adjustment will usually permit the desired concentration to be achieved. If this is... 

During nebulization from airjet nebulizers, cooling of the reservoir solution occurs which, together with vapor loss, results in concentration of the dmg solution. This in turn produces an aerosol output in which the drag concentration increases with time. Concentration of the dmg solution in the reservoir can lead to drug recrystallization with subsequent blockage within the device or variation in aerosol particle size. 

Therapeutic doses from an aerosol are free of systemic adverse effects because of the very low blood concentration after inhalation. Transient dryness of the mouth and scratching in the trachea can occur in up to 25% of patients receiving wet nebulizer treatment with the drug. 

The concentrations of the drug at the desired sites and at the sites of toxicity within the respiratory tract will depend on the balance of the drug supply and clearance rates at these sites [37]. We may speculate that this is one of the reasons for the higher doses required for the delivery of topical medications by nebulizers (typically over 10-25 min) vs. metered-dose inhalers or dry powder inhalers that deliver the medication in one or two breaths. There is little doubt that prolonged inhalation reduces the patient s enthusiasm for the therapy. It is therefore appropriate to evaluate nebulizers in terms of their useful output, that is, the dose of the therapeutic or diagnostic agent delivered in the desired aerodynamic size range per unit time [145]. 

For inhalation treatment of respiratory diseases, a pharmaceutical DNase I aerosol is on the market. Pulmozyme is a sterile solution for respiratory use at a concentration of 1000 Genentech Units/mL [22]. It contains 1 mg/mL rhDNase, sodium chloride as a tonicity modifier, calcium chloride as a stabilizer, and water for injection. Since deamidation is rapid at high pH and aggregation occurs at low pH, a nearly neutral solution (pH 6.3) is required. It is administered by means of a compressed air-driven nebulizer. Each 2.5-mL single-unit ampule will deliver 2.5 mg of rhDNase to the nebulizer chamber. The efficacy of DNase inhalation therapy largely depends on the aerosol quality and characteristics, which determine the respirable fraction. Significant differences were found between the different aerosol drug-delivery systems [68,81]. 

ABSORPTION, FATE, AND EXCRETION Epi is ineffective after oral administration because it is rapidly metabolized in the GI mucosa and liver. Absorption from subcutaneous tissues occurs relatively slowly because of local vasoconstriction, and the rate may be further decreased by systemic hypotension e.g., in shock). Absorption is more rapid after intramuscular injection. In emergencies, it may be necessary to administer Epi intravenously. When relatively concentrated solutions (1%) are nebulized and inhaled, the actions of the drug largely are restricted to the respiratory tract however, systemic reactions such as arrhythmias may occur, particularly if larger amounts are used. 

The mast cell stabilizers are used in combination widi other drugs in the treatment of asdima and odier allergic disorders, including allergic rhinitis (nasal solution), and in the prevention of exercise-induced bron-chospasm. When die mast cell stabilizers are used in conjunction widi odier antiasdima dni, a reduction in dosage of die dni may be possible after using die mast cell stabilizer for 3 or 4 weeks. These dni may be given by nebulization, aerosol spray, or as an oral concentrate... 

The air entering the nebulizer is normally not humidified, and the large concentration of aerosol water droplets circulating in the device results in rapid two-way coupled mass transfer that causes droplet evaporation and humidification of the air. The latent heat associated with this evaporative mass transfer causes cooling of the liquid in the reservoir over time, and the humidification of the compressed air increases the concentration of the drug in the nebulizer reservoir over time [3, 16]. 

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