Thermoanalytische Methoden zur Abschätzung der Stabilität von Komponenten zur Pulverinhalation
In this study different compounds that are established as substances for dry powder inhalations have been examined by means of thermoanalytical techniques. The re-crystallization behaviour of amorphous lactose has been investigated by isothermal microcalorimetric measurements. Considering the enthalpies of re-crystallization, desorption and solution the influence of the chosen relative humidity, the amount of amorphous lactose and the presence of seed crystals has been determined. The amorphous and anhydrous form of ipratropium bromide monohydrate has been produced and physico-chemically characterized. Thermoanalytical measurement techniques have been applied to predict crystallization behaviour in terms of stability. The polymorphic forms of Salmeterolxinafoate have been investigated by differential scanning calorimetry (DSC) and powder x-ray diffractometry (XRPD). SX I has been produced in a very pure manner by the ASES (Aerosol Solvent Extraction System)-process and SX II has been gained by the crystallization of the melt. Furthermore stability tests of both polymorphic forms have been carried out. Ordered mixtures composed of alpha lactose monohydrate as a carrier (Pharmatose 325M®); ipratropium bromide monohydrate and micronized amorphous lactose have been investigated in terms of their fine particle fraction (FPF). Low dosed powder formulations show that the FPF distinctively improves if a pre- mixture has been pre-stored at 58% RH and 75% RH, respectively, and subsequently been mixed with ipratropium bromide.