A critical evaluation of the relevant parameters for drug redispersion from adhesive mixtures during inhalation.
In this paper, the parameters that are relevant to the drug redispersion from adhesive mixtures during inhalation are discussed and evaluated. The results obtained with air classifier technology give strong evidence for a dominating influence of carrier surface properties on the fraction of drug detached during inhalation at a low carrier payload (< or =1%, w/w), versus a dominating effect of carrier bulk properties at higher payloads. Furthermore, the results indicate that there is a fundamental difference between so-called active carrier sites and large surface discontinuities. The difference refers to the saturation concentrations, the rates of saturation and their effects on drug detachment during inhalation. The degree of saturation of the active sites appears to be proportional with the square root of the carrier surface payload (after 10 min mixing time in a Turbula mixer at 90 rpm). The storage volume of the discontinuities seems largely independent of the carrier diameter for particles derived from the same batch of crystalline lactose. Saturation of these discontinuities is completed at a much lower carrier surface payload than saturation of the active sites. Relatively large discontinuities are beneficial to de-agglomeration principles that make use of inertial separation forces during inhalation, as they provide shelter from inertial and frictional press-on forces during mixing which increase the strength of the interparticulate bonds in the powder mixture. For de-agglomeration principles generating frictional, drag or lift forces, carrier surface depressions and projections are disadvantageous however, as they also provide shelter from these removal forces.
de Boer
A H
AH
Department of Pharmaceutical Technology and Biopharmacy, Groningen University Institute for Drug Exploration (GUIDE), Ant. Deusinglaan 1, 9713 AV Groningen, The Netherlands. A.H.de.Boer@rug.nl
Dickhoff
B H J
BH
Hagedoorn
P
P
Gjaltema
D
D
Goede
J
J
Lambregts
D
D
Frijlink
H W
HW
D000269:Adhesives / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000280:Administration, Inhalation; D004337:Drug Carriers / Q000008:administration & dosage* / Q000493:pharmacokinetics*
D000269:Adhesives; D004337:Drug Carriers