Characterization of Radiolabeled Dry Powder Leucine, a Constituent of Inhalable Capreomycin

Lindie      Venter; Judith      Wagener; P.      Bernard Fourie; Jan      Rijn Zeevaart

doi:10.2174/2210304x11202030155

Abstract

Reformulation of anti-tuberculosis drugs into dry powder particles for inhalation is a novel strategy that aims to increase therapeutically relevant drug concentration at the primary site of infection and to limit associated toxicity by avoiding or minimizing first-pass metabolism. Development of such formulations ultimately requires quantified evidence of the deposition, absorption and clearance of inhaled active ingredient. In this context, we investigated the potential of radiolabelling particles with 153Sm for subsequent gamma imaging, and to demonstrate that the technique is not detrimental to particle integrity. The study showed that the known properties of spray dried leucine (a major constituent of an inhalable capreomycin formulation) for deep lung inhalation are not altered by incorporation of samarium-chloride (SmCl3) at 10% (w/w), or by neutron activation of particles that include stable 152SmCl3. SEM imaging indicated that the particle morphology was homogeneous and spherical after neutron activation. No discoloration of the samples or a change in dry powder particle size at 5 minutes occurred, provided the optimized formulations were activated for only 1 minute. Activation for 1 minute still provides enough 153Sm for imaging purposes.

Keywords: Gamma imaging, 153Sm radiolabel, spray dried powder particles, pulmonary drug delivery, tuberculosis, leucine, capreomycin, human immunodeficiency virus (HIV), multi-drug resistance, Neutron Activation, Chemical, Reagents, chromatography (HPLC), Samarium Formulation, homogeneous.