title: New method for easy labeling of beta-2-agonists in the metered dose inhaler with technetium 99m.
abstract: The actual deposition pattern of micronized drugs from metered dose inhalers (MDI) is incompletely known because there are no methods available to label the drugs (beta 2-agonists) with gamma-emitters. Indirect measurements of the distribution of the drug in man differed greatly due to the method used. Our method uses the better solubility of 99mTcO4- in the beta 2-agonist-micronized drug in relation to the propellant with surfactant. The principle is to extract the 99mTcO4- from the original water phase into the liquid phase of the propellant with ethyl methyl ketone. For labeling the micronized drug particles, the original MDI must be cooled to -60 degrees C and some labeled propellant (including surfactant) with high specific activity of 99mTcO4- is added through an aperture in the bottom of the container. The aperture is sealed with a screw. After rewarming the MDI, more than 90% of the added 99mTcO4- is dissolved in the beta 2-agonist-micronized drug in relation to its volume. This is proved by comparing the distribution of the radioactivity component with chemical analysis. The pattern of deposition of both MDIs - placebo and beta 2-agonist-micronized drug - was shown to be similar in healthy volunteers. With a labeled MDI a preliminary study with 2 different inhaling maneuvers was performed in 7 volunteers: inhaling from residual volume after a pause of 2 s the intrabronchial deposition was 18.7%, and inhaling at 50% of vital capacity maneuver the intrabronchial deposition was 33.0%. The data obtained with actual measurement of the inhaled drug from MDI suggest greater intrabronchial deposition than was assumed before in the literature.
mesh_terms: D000318:Adrenergic beta-Agonists; D000336:Aerosols; D000420:Albuterol; D002074:Butanones; D005280:Fenoterol; D006801:Humans; D007553:Isotope Labeling / Q000379:methods*; D008168:Lung / Q000000981:diagnostic imaging; D009330:Nebulizers and Vaporizers; D009960:Oropharynx / Q000000981:diagnostic imaging; D011877:Radionuclide Imaging; D013667:Technetium
chemical_list: D000318:Adrenergic beta-Agonists; D000336:Aerosols; D002074:Butanones; D005280:Fenoterol; C005222:methylethyl ketone; D013667:Technetium; D000420:Albuterol