Analysing the Nano-Structure Properties of a Drug Release Coating Using nano-TA Thermal Probe from Anasys Instruments

Topics Covered

Background
Nano Thermal Analysis
Experimental Setup
Results and Discussion
Contact Mode Imaging
Tapping Mode Imaging
Localized Thermal Analysis
Conclusions
Acknowledgements

Background

Blends of hydroxypropyl methylcellulose (HPMC) and ethyl cellulose (EC) are widely used as coatings for solid dosage forms to control drug release rates. This study aims to map and determine the morphological properties of a phase-separated HPMC/EC blend at the nanometer scale using a new nanothermal analysis (nano-TA thermal probe) technique, thus providing further understanding of the nature of the intermolecular interactions between the components in the blend.

Nano Thermal Analysis

Nano-TA thermal probe is a local thermal analysis technique which combines the high spatial resolution imaging capabilities of atomic force microscopy with the ability to obtain an understanding of the thermal behaviour of materials with a spatial resolution of sub-100nm. (a breakthrough in spatial resolution ~50x better than the state of the art). The conventional AFM tip is replaced by a special nano-TA thermal probe probe that has an embedded miniature heater and is controlled by the specially designed nano-TA thermal probe hardware and software. This nano-TA thermal probe probe enables a surface to be visualised at nanoscale resolution with the AFM's routine imaging modes which enables the user to select the spatial locations at which they would like to investigate the thermal properties of the surface. The user then obtains this information by applying heat locally via the probe tip and measuring the thermomechanical response.

Experimental Setup

Blends were prepared by dissolving a mixture of 1:1 wt / wt HPMC / EC in a solution of 50:50 by volume of methanol/dichloromethane at a concentration of 10% wt / vol. Following solvent evaporation, the blends were sectioned using an ultramicrotome to analyse the internal morphology. The nanoscale thermal results were obtained using a Multimode AFM (Nanoscope IIIa) equipped with an Anasys Instruments (AI) nano-thermal analysis (nano-TA thermal probe) accessory and AI micro-machined thermal probe. Imaging and localised thermal analysis (LTA) spatially accurate at the 100nm scale was performed. The contact and tapping modes were used to acquire surface images and LTA employed to determine the glass transition temperature (Tg) of the different domains at a 10°C /s heating rate.

The nano-TA thermal probe data presented are the cantilever deflection (while the probe is in contact with the sample surface and the feedback turned off) plotted against the probe temperature. This measurement is analogous to the well established technique of thermo-mechanical analysis (TMA) and is known as nano-TA thermal probe. Events such as melting or glass transitions that result in the softening of the material beneath the tip, produce a downward deflection of the cantilever. Further information on this technique can be obtained at www.anasysinstruments.com.

Results and Discussion

Contact Mode Imaging

Figure 1 demonstrates the imaging capability of the new nanothermal probe in contact mode. The height image clearly shows the phase-separated structure of the blend, consisting of a continuous matrix and discrete domains. The size of these domains varies from approx. 200 nm to the micro-meter scale.

Figure 1. Height image - Scan size (50 x 50 µm)

Tapping Mode Imaging

Figure 2 demonstrates the capability of the nano-TA thermal probe probe for tapping mode imaging. The height image (left) shows a similar two-phase structure as revealed in contact mode imaging. The phase image shown on the right, taken simultaneously in the tapping mode, also shows a difference in contrast. In general, the discrete domains appear bright whereas the continuous phase is dark. The contrast in the image observed represents a variation in the properties of these two phases, but does not unequivocally identify the composition of the two phases.

Figure 2. Height (left) and phase (right) images (4 x 4 µm scan)

Localized Thermal Analysis

Localised thermal analysis was used to determine the transition temperature of specific areas of a sample for identification. It was performed by pinpointing the probe to a location on an image. In this study, it was determined that the glass temperature (Tg) of the matrix transition (Figure 3) was approximately 220°C, and of the separated phase approximately 180°C. The difference between these two Tg values coincides with the subtraction result between the Tg value of the pure HPMC (162°C[1]) and EC (125°C[2]) which was measured with DSC. The result indicated that the discrete phase is predominantly EC and the continuous matrix the HPMC component. The difference in the absolute value of the Tg determined with nano-TA thermal probe and DSC may be mainly caused by the high heating rate.

Figure 3. Localised thermal analysis on the matrix and domains

Conclusions

A HPMC/EC blend has been analyzed using AFM combined with nano thermal analysis. The AFM images clearly showed a bi-phasic structure, but it was not clear from the topography images which material was which domain. Also, it was not clear whether the domains were completely phase separated or just different mixtures of the two components. The nano-TA thermal probe allowed us to clearly determine that the matrix was the HPMC component and the domains the EC component. Also because the separation between the transitions was the same as measured for the two components individually in bulk, it indicated a complete incompatibility between HPMC and EC. The fact that the two components phase segregate at this scale is important to the usage of this material as a drug coating as the degree of separation can be used to control the release rate of a drug.

Acknowledgements

Anasys Instruments would like to thank Molecular Profiles for allowing us to extract this application note from the poster titled "Nano-Structure Properties of a HPMC/EC Polymer Blend Resolved Using Nanothermal Analysis" which was presented at AAPS, San Antonio in October 2006.

Source: Anasys Instruments

For more information on this source please visit Anasys Instruments

Date Added: Feb 18, 2008 | Updated: Jun 11, 2013
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