Linking the structural properties of adhesive mixtures to their observed powder mechanics
Jonas Rudén1, Göran Frenning1, Tobias Bramer2, Kyrre Thalberg2 & Göran Alderborn1
1Department of Pharmacy, Uppsala University, Husargatan 3, Box 580, Uppsala, SE-751 23, Sweden
2Pharmaceutical technology and development, AstraZeneca R&D Gothenburg, Pepparedsleden 1, Mölndal, 431 83, Sweden
Mixing larger particles (carriers) with smaller particles (fines) to produce an adhesive, or ordered, mixture is a formulation technique used to promote powder flow and reduce the risk of segregation during handling and use. Within the dry powder inhalation (DPI) field, this technique is extensively used as a means of counteracting the cohesive nature of micronized APIs. In order to better understand the interaction between these two dissimilar components the main objective of this study was to investigate the relationship between the content of fine particles and the observed powder mechanics of binary adhesive mixtures and link these observations to a powder structure assessed by imaging techniques.
The mixtures, consisting of lactose, contained one carrier (Lactopress SD) and increasing amounts of fine particles corresponding to different surface coverage ratios (SCR). From the powder mechanics analysis, combined with scanning electron microscopy (SEM), it was found that the fine particles predominantly gather in the cavities of the carrier particles at low SCR (0.25), which effectively increases the carrier particle density and makes the carrier surfaces smoother. This phenomenon was shown to increase the packing density of the mixture and reduce the sensitivity to pressure. Adding more fines beyond a SCR of 0.25 instead leads to a more disordered structure of fine and carrier material, as confirmed by environmental scanning electron microscope images (ESEM). This increasingly disordered structure leads to a gradually reduced packing density and an increased sensitivity to pressure.