Pulmonary deposition of lactose carriers used in inhalation powders.
Dry powder dosage forms are generally formulated by mixing the micronized drug particles with the larger carrier particles. Lactose is a commonly used carrier. Carriers enhance the flowability of powder mixtures and therefore enable low dosing of active substances. During inhalation, the drug particles are dispersed from the surface of carrier particles. The aim of this study was to compare how different qualities of 99mTc-labelled lactose carrier systems deposit in the lungs. The sizes of the labelled and unlabelled alpha-lactose monohydrate particles were compared by using a laser diffraction method. Distribution of radiolabel between different particle size fractions was determined using the Andersen cascade impactor. The in vivo depositions of lactose carrier systems were investigated in ten healthy men using the technique of gammascintigraphy. In addition, redispersion of budesonide from the carrier materials was evaluated by using the Andersen cascade impactor. According to the validation data the particle size of the lactose carriers remained unchanged during the labelling process. Low pulmonary deposition varying between 2.5 and 3.3% was detected. Only a small amount of lactose was deposited in the lungs, thus pulmonary deposition is not a limiting factor for lactose selection. According to in vitro redispersion data the fine particle fraction of the delivered dose in the impactor varied between 10.3 and 26.0%. Thus, the redispersion of the budesonide particles can be altered by the properties of the carrier system.
Karhu
M
M
Department of Pharmaceutics, University of Kuopio, P.O. Box 1627, Kuopio, Finland. mika.karhu@orion.fi
Kuikka
J
J
Kauppinen
T
T
Bergström
K
K
Vidgren
M
M
D000280:Administration, Inhalation; D000328:Adult; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D019819:Budesonide / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D004337:Drug Carriers; D005079:Excipients / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D007553:Isotope Labeling; D007785:Lactose / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D008168:Lung / Q000000981:diagnostic imaging / Q000378:metabolism*; D008297:Male; D015609:Organotechnetium Compounds / Q000138:chemical synthesis; D010316:Particle Size; D011208:Powders; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals
D001993:Bronchodilator Agents; D004337:Drug Carriers; D005079:Excipients; D015609:Organotechnetium Compounds; D011208:Powders; D019275:Radiopharmaceuticals; D019819:Budesonide; D007785:Lactose