Highly loaded interactive mixtures for dry powder inhalers: prediction of the adhesion capacity using surface energy and solubility parameters.
In order to correlate drug adhesion properties of a highly loaded interactive mixture for the use in dry powder inhalers with the surface energy and to establish a link to the solubility parameter, surface free energy was detected for micronized substances (salbutamol sulfate, salbutamol base, theophylline and alpha-lactose monohydrate) using inverse gas chromatography (IGC). Interactive mixtures with coarse crystalline alpha-lactose monohydrate as a carrier were prepared at loading levels from 7.5 to 20% (w/w) and analyzed with respect to their adhesion capacity (CA) using the air jet sieving method. Solubility parameters were taken from literature or calculated. As a result the CA was independent of the drug load and correlated linearly with volume specific surface energy interaction (SEIv) values of the adherents (R2 = 0.98498). A link between SEIv and the size normalized solubility parameter (delta(tot)/d50) was found. Consequently, plotting delta(tot)/d50 versus CA resulted also in a strong linear relationship (R2 = 0.99140). Overall a powerful tool was established to judge and quantify adhesion properties of highly loaded interactive mixtures even for estimates in early preformulation at a time where just the molecular structure of the active ingredient is known.
Wagner
K G
KG
Lehrstuhl für Pharmazeutische Technologie, Universität Tübingen. karl.wagner@uni-tuebingen.de
Dowe
U
U
Zadnik
J
J
D000268:Adhesiveness; D002626:Chemistry, Pharmaceutical; D002849:Chromatography, Gas; D005079:Excipients; D007208:Indocyanine Green; D007785:Lactose; D009330:Nebulizers and Vaporizers; D010316:Particle Size; D011208:Powders; D012044:Regression Analysis; D012995:Solubility; D013499:Surface Properties
D005079:Excipients; D011208:Powders; D007208:Indocyanine Green; D007785:Lactose