Characterisation of particle-particle interactions using the atomic force microscope
An investigation has been conducted into factors affecting the interparticulate cohesion profile of three micronised drugs, as a function of humidity. An atomic force microscope (AFM) colloid probe technique was correlated with physico-chemical properties and in-vitro performance. Briefly, micronised drug particles of salbutamol sulphate, triamcinolone acetonide (TAA) and disodium cromoglycate (DSCG) were mounted onto Vshaped tipless cantilevers using a developed micromanipulation technique. Interactions between the AFM ‘drug probes’ and a series of model drug surfaces were conducted at a 15,30, 45, 60 and 75% relative humidity using a custom built perfusion apparatus connected to the AFM. As expected, separation energy distributions for drug probe interactions were dependent on the surface rugosity of the drug model surfaces. Separation energy measurements conducted between drug probes and individual micronised drug particles (mounted in polymer resin) suggested large variations in separation energy. Further analysis of such data suggested a lognormal separation energy distribution, however, limitations in individual particle measurements (finite particle measurements per experiment) allowed restricted statistical analysis.