New Method for Easy Labeling of Beta-2-Agonists in the Metered Dose Inhaler with Technetium 99 m

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 (β₂-agonists) with γ-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 ^99mTcO^-₄ in the β₂-agonist-micronized drug in relation to the propellant with surfactant. The principle is to extract the ^99mTcO^-₄ 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 °C and some labeled propellant (including surfactant) with high specific activity of ^99mTcO^-₄ 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 ^99mTcO^-₄ is dissolved in the β₂-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 β₂-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.

Washing plastic spacers in household detergent reduces electrostatic charge and greatly improves delivery

“…Salbutamol (Ventolin1) was labelled with 99m Tc following the method of KO È HLER et al [15], with some modifications. Technetium pertechnetate ( 99m TcO 4 -; 500±600 MBq) was eluted from a radionuclide generator (Australian Radioisotopes, Lucas Heights, NSW, Australia) and added to 4 mL butanone in a separating funnel.…”

Improved airway targeting with the CFC-free HFA-beclomethasone metered-dose inhaler compared with CFC-beclomethasone

“…The radiolabelling method [13] was modified from the methods of FEW et al [14], KÖHLER et al [15] and NEWMAN et al [16]. Technetium-99m ( 99m Tc) was obtained from a commercial vendor as sodium pertechnetate (Na 99m TcO 4 ) in saline.…”

A New Aerosol Device for Bronchial Provocation Tests

“…The method of choice to measure pulmonary drug de position in vivo is the inhalation of radioactive aerosols with a particle-volume-related gamma-emitting tracer (W mTc) [3],…”