The Cohesive-Adhesive Balances in Dry Powder Inhaler Formulations I: Direct Quantification by Atomic Force Microscopy

Abstract

The novel approach provides a fundamental insight into the cohesive-adhesive balances in dry powder formulations and further understanding of powder behavior.

Characterisation of dry powder inhaler formulations using atomic force microscopy

“…Elasticity (Davies et al, 2005;Perkins et al, 2009Perkins et al, , 2007 Deformation (local) Hardness (Masterson and Cao, 2008;Perkins et al, 2009) Degradation during storage or processing (Perkins et al, 2009) Force distance measurements Elastic modulus Elasticity (Davies et al, 2005;Perkins et al, 2009, 2007 Hardness (Masterson and Cao, 2008;Perkins et al, 2009) Adhesion Degradation during storage or processing (Perkins et al, 2009) Crystallinity (Perkins et al, 2007) Particle surface energetics (Davies et al, 2005;Perkins et al, 2009) Chemical surface properties (Hooton et al, 2004) Correlation of surface specific properties (Perkins et al, 2007;Ward et al, 2005) Colloidal probe AFM Adhesion Physical interaction between materials (Beach et al, 2002;Hooton et al, 2004;Rogueda et al, 2011) Chemical interaction between materials (Hooton et al, 2004;Islam et al, 2014;Rogueda et al, 2011) Cohesive adhesive balance (Begat et al, 2004a;Jones et al, 2008a,b) Particle surface energetics (Hooton et al, 2006a) Electrostatic surface properties (Götzinger and Peukert, 2003;Kwek et al, 2011) Triboelectric charging (Kwek et al, 2011) Surface polarity (Kwek et al, 2011) Fig. 1.…”

“…Researchers rely on the root mean square (RMS) roughness (Berard et al, 2002a,b;Bouhroum et al, 2010;Hickey et al, 2007;Hooton et al, 2006a,b;Traini et al, 2006;Young et al, 2009), and sometimes also include the arithmetic average (Begat et al, 2004a;Kinnunen et al, 2014).…”

“…Again, additional layers of magnesium stearate and leucine, spin-coated onto the polymer surface, had an anti-adherent effect. Begat et al (2004a) used the colloidal probe technique to measure the CAB within dry powder formulations. CAB measurements, which assess the ratio of the cohesive and adhesive interaction of API and carrier particles, were first introduced by Nanopharm Ltd. (Nanopharm Ltd., 2009).…”

“…Begat et al (2004a) made use of the colloid probe technique to observe the CAB ratio in DPI formulations of salbutamol sulphate and budesonide with the carrier material lactose. To reduce the effects of roughness budesonide, salbutamol sulphate and lactose were crystallised by primary nucleation from solution.…”

“…To reduce the effects of roughness budesonide, salbutamol sulphate and lactose were crystallised by primary nucleation from solution. CAB graphs were used to describe the dominating forces in the drug/carrier system and also to demonstrate the capability, reproducibility and applicability of AFM and CAB measurements (Begat et al, 2004a). The CAB technique also served to explain substantial differences in the fluidisation and aerosolisation of poorly and highly cohesive drug particles.…”