1 Copyright © 2011, Elsevier Inc. All rights Reserved. Atomic Force Microscopy for Characterization of Surfaces, Particles, and Their Interactions Chapter 6 Frank M. Etzler and Jaroslaw Drelich

2 Copyright © 2011, Elsevier Inc. All rights Reserved. FIGURE 6.1 Schematic drawing of an atomic force microscope. The scanner moves in three directions and the deflection of the cantilever is detected by the photodetector.

3 Copyright © 2011, Elsevier Inc. All rights Reserved. FIGURE µm 5 µm images of topography (left) and phase (right) for polyurethane/polyethylene composite. The Z-scale was 200 nm (topography) and 150° (phase), and the drive phase is 40°. The dark circles in the phase image show the areas of high concentration polyurethane (dispersed phase, nodular shape, diameter: 0.5–1.5 µm). The bright continuous areas indicate polyethylene (matrix phase, continuous area).

4 Copyright © 2011, Elsevier Inc. All rights Reserved. FIGURE 6.3 Hypothetical force curve for probe–surface interaction. Dashed curve represents probe advancing toward surface. Solid curve represents probe receding from surface. A is probe snap-off force representing the force of adhesion between probe and surface. C is the probe surface contact position with advancing motion. The shaded area has sometimes been used as a method for determining the adhesion strength [19].

5 Copyright © 2011, Elsevier Inc. All rights Reserved. FIGURE 6.4 Left – AFM cantilever tip. Right – AFM cantilever with lactose particle mounted as a colloidal probe.

6 Copyright © 2011, Elsevier Inc. All rights Reserved. FIGURE 6.5 Comparison of particle diameters determined by AFM to other methods. Left axis – particles on impactor plates. Plate number is given on x-axis. Data on the left axis by Gwaze et al. [42]. Right axis comparison particle diameters were determined by AFM and TEM. Data on the right axis by Lacava et al. [45].

7 Copyright © 2011, Elsevier Inc. All rights Reserved. FIGURE 6.6 Pull-off force of insulin particles on PP and ABS surfaces versus relative humidity. Figure redrawn from data by Beach and Drelich [51]. Results indicate that surface roughness and capillary forces contribute significantly to the adhesion force. See text and original work [51] for details.

8 Copyright © 2011, Elsevier Inc. All rights Reserved. FIGURE 6.7 Height and friction images of gelatin capsule surfaces [32]. Surfaces are from interior of the capsule. Capsules from Manufacturer A have pits in the surfaces that presumably result from bubbles entrapped near the surface during capsule manufacture. Light areas in the friction image result from surface contamination by mold release agent.

9 Copyright © 2011, Elsevier Inc. All rights Reserved. FIGURE 6.8 Adhesion force of lactose particles on capsule surfaces [54]. Numbers in legend are capsule lot numbers. Upper curve represents normal capsules (Manufacturer A) and lower curve represents capsules cleaned with supercritical CO 2, or capsules made by Manufacturer B. Capsules that have clean surfaces exhibit lower adhesion force.

10 Copyright © 2011, Elsevier Inc. All rights Reserved. FIGURE 6.9 Surface free energy parameters for various lots of lactose as determined using IGC [52]. γ LW is the Lifshitz –van der Waals component of the surface free energy. K a and K d are the acid and base parameters describing the lactose surface using Gutmanns acid–base model (see Etzler [40] for an explanation of acid–base models). The figure suggests that the surface chemistry of various lots of lactose is variable.

11 Copyright © 2011, Elsevier Inc. All rights Reserved. FIGURE 6.10 Surface acidity (K a ) for various lots of lactose and retention in capsule for various lots of lactose versus ratio of OCO carbons to aliphatic (CH) carbons on lactose surfaces [52]. CH carbons represent surface contamination. The oxidation states of surface carbons were determined using x-ray photoelectron spectroscopy (XPS) (or ESCA, Electron Spectroscopy for Chemical Analysis).

12 Copyright © 2011, Elsevier Inc. All rights Reserved. FIGURE 6.11 Phase image of lactose surface showing surface contamination (dark area and white specks) [54].

13 Copyright © 2011, Elsevier Inc. All rights Reserved. FIGURE 6.12 Normalized adhesion force (F/R) between drug (Ibr) and lactose particles with other particles and surfaces [54]. Both normal capsules (Cap) and cleaned capsules (Cap E) were studied. Normalized force is the measured force divided by particle radius. Particle – capsule interactions are strongest. Drug – capsule interactions are stronger than lactose capsule interactions.

14 Copyright © 2011, Elsevier Inc. All rights Reserved. FIGURE 6.13 In-vitro deposition measurements of the percentage of dose retained in device (% Ret. Device), the fine particle fraction relative to the emitted dose (% FPF ED), and fine particle fraction relative to the total dose (% FPF Total) for salbutimol and mixtures of salbutimol with force control agents. Figure redrawn from the data by Begat et al. [55]. Addition of a flow control agent has a small effect on retention of the powder in the device, but significantly reduces adhesion between particles, thus improving dispersion of the powder and FPF.

15 Copyright © 2011, Elsevier Inc. All rights Reserved. FIGURE 6.14 Normalized adhesion force for chemically modified AFM tips against modified surfaces. Modification reagents are CH-octyltrichlorosilane, COC-3-methoxy propyltrimethoxysilane and COOC-2-acetoxyethyltrichlorosilane. Non-CH-modified surfaces are vastly different in hydrocarbon and HFA media. COC and COOC allow for more interaction with HFA media and show lower forces than CH in this media.

16 Copyright © 2011, Elsevier Inc. All rights Reserved. FIGURE 6.15 Height (left) and phase (right) images of Al canister used for an MDI formulation. A 10 μm 10 μm area is shown. Banding pattern is clearly observed in the phase image and presumably results from the canister manufacturing process.

17 Copyright © 2011, Elsevier Inc. All rights Reserved. FIGURE 6.16 Topographic (left) and phase image (right) of a silicon wafer contaminated with an oil that came from a dust-remover moisture-free cleaning can, commonly used in coarse cleaning of substrates (E. Beach and J. Drelich, unpublished work).