Stability of Formoterol as model for a reduction-sensitive material in blends for inhalation

N Rhein¹, G Birk², U. Girreser³, R Scherließ¹

¹Department of Pharmaceutics and Biopharmaceutics, Kiel University, Grasweg 9a, 24118 Kiel, Germany

²Merck KGaA, Frankfurter Straße 250, 64293 Darmstadt, Germany

³Department of Pharmaceutical/Medical Chemistry, Kiel University, Gutenbergstrasse 76, 24118 Kiel, Germany

The delivery of micronized drugs to the lungs is challenging as these powders are typically highly cohesive and therefore exhibit poor flowability. To improve these properties, carrier-based powder blends are used and lactose is the typical carrier, although alternative carriers such as mannitol are in consideration. In comparison to lactose, a reducing sugar, mannitol has a very low content of reducing sugars, which may be especially important in combination with reduction-sensitive drugs such as active pharmaceutical ingredients (APIs) with a primary or secondary amine group. In this study formoterol fumarate dihydrate served as model API to elucidate the potential of a stability-reducing Maillard reaction in combination with different carrier materials via liquid chromatography-mass spectroscopy. Results show that the secondary amine formoterol decomposes to the primary amine independently of reaction partners, whereas a Maillard reaction (Amadori product) was only found in combination with lactose.