Direct observation of single particle electrostatic charging by atomic force microscopy.

PURPOSE: To show that atomic force microscopy (AFM) can be used to directly study the electrostatic charging and dissipation of single pharmaceutical particles. MATERIALS AND METHODS: Particles of lactose attached to AFM cantilevers were charged on a glass surface at a relative humidity (RH) of 0.1%. By recording force-distance curves, we use a measurement of the long range electrostatic interaction to compare the generation of charge by contact charging and tribocharging and to study the effect of RH on charge dissipation. RESULTS: As expected, tribocharging by scanning the particle across the glass surface generates considerably more charge than repeated local contacts. Increasing the RH from 0.1 to 5% over a period of 37 min dissipates the tribo-generated electrostatic charge. CONCLUSIONS: Using a combination of the abilities of AFM to scan in contact mode and record force-distance curves, we have shown a novel method to study electrostatic charging of particles. By measuring the length of the long range electrostatic interaction, we are able to compare different mechanisms of generating charge and to study the effect of RH on charge dissipation.

Single particle friction on blister packaging materials used in dry powder inhalers.

Using atomic force microscopy (AFM) the adhesion and sliding friction behaviour of single lactose particles attached directly to AFM cantilevers has been studied. Measurements were made on the two sides of a blister packaging material used in dry powder inhalers (DPI). Although no significant differences in adhesion were observed, clear differences in particle friction were evident, where one side offers consistently greater friction across the range of loads studied here. The packaging samples were characterised by time-of-flight secondary ion mass spectrometry (ToF-SIMS) and X-ray photoelectron spectroscopy (XPS) and found to have different surface chemistries. The observed difference in friction behaviour is discussed in the context of the differences seen in surface chemistry, topography and hardness. It is reasoned that in this case hardness has the largest influence, and on one sample soft surface layers are displaced by the particle. A clear relationship between friction and load was only observed with one of the three particles tested; this was attributed to multiple asperities being brought into contact, illustrating the important role of nanoscale contact geometry in determining friction behaviour.

A nanoscale study of particle friction in a pharmaceutical system.

Studies of single particle interactions in dry powder inhaler (DPI) formulations using atomic force microscopy (AFM) have recently grown in popularity. Currently, these experiments are all based on measuring particle adhesion forces. We broaden this approach by presenting a novel AFM friction study of single particles in a pharmaceutical system, to examine forces acting parallel to a surface. The sliding friction signal of lactose particles attached to AFM cantilevers was recorded in lateral force (LF) mode over 5 microm x 5 microm areas on five different surfaces chosen to represent both relevant inter-particle and particle-surface interactions. A ranking of friction forces was obtained as follows: glass approximately equal to zanamivir >zanamivir-magnesium stearate (99.5%/0.5%, w/w) blend approximately equal to magnesium stearate approximately equal to PTFE. The addition of magnesium stearate to the zanamivir surface dominated and significantly reduced the friction (Kruskal-Wallis test, P<0.001). AFM images of the contacting asperities of the lactose particles show changes in contact morphology due to two processes. Firstly the asperity wears flat due to abrasion and secondly small magnesium stearate particles transfer onto the asperity. It is proposed that in combination with AFM particle adhesion measurements, this method could be used to screen new formulations and the effectiveness of tertiary components in modifying carrier-drug interactions.