New method for easy labeling of beta-2-agonists in the metered dose inhaler with technetium 99m.

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.