The effect of budesonide particle mass on drug particle detachment from carrier crystals in adhesive mixtures during inhalation.
The different fine particle fractions (FPFs) that are obtained, when different dry powder inhalers (DPIs) are used for the same powder formulation at the same flow rate, is the result of different powder de-agglomeration efficiencies for these DPIs. For adhesive mixtures, this is the efficiency with which the kinetic energy of the air flow through the DPI is converted into separation forces that detach drug particles from carrier crystals. We investigated the effect of drug particle diameter (mass) on drug-carrier separation during inhalation with three different inhalers (Sofotec Novolizer, Inhalator Ingelheim and a special test inhaler), at two different flow rates (30 and 60l/min). Two different size fractions were used as carrier material (45-63 and 100-150 microm). We measured decreasing amounts of residual drug on the carrier crystals after inhalation with increasing drug particle mass for all inhalers at both flow rates. The observed trends were the same for both carrier fractions. The decrease in residual drug on carrier is in agreement with increasing FPFs in an Erweka impactor. However, it has been calculated that the magnitude of the effect decreases with increasing de-agglomeration efficiency.
Department of Pharmaceutical Technology and Biopharmacy, Groningen University Institute for Drug Exploration (GUIDE), Groningen, The Netherlands. b.h.j.dickhoff@farm.rug.nl
B H J
BH
Dickhoff
M J H
MJ
Ellison
A H
AH
de Boer
H W
HW
Frijlink
D000269:Adhesives / Q000737:chemistry; D000280:Administration, Inhalation; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000737:chemistry*; D019819:Budesonide / Q000008:administration & dosage / Q000737:chemistry*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003460:Crystallization; D004337:Drug Carriers / Q000737:chemistry; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D011208:Powders / Q000737:chemistry
D000269:Adhesives; D001993:Bronchodilator Agents; D004337:Drug Carriers; D011208:Powders; D019819:Budesonide