Perichromism: a novel technique to distinguish between amorphous and crystalline material

Major, Patrick J. (2010) Perichromism: a novel technique to distinguish between amorphous and crystalline material. PhD thesis, University of Greenwich.

Abstract

To distinguish between amorphous and crystalline material, 0.1% w/w phenol red, was added to sucrose, and dissolved in water. The solution was frozen before being freeze-dried, and the resultant amorphous excipient, with probe incorporated, was split into eight equal masses. The samples were then stored at controlled temperature and at a relative humidity unique to each sample. After storage for one week, there were two distinct groups. Diffuse reflectance ultraviolet spectroscopy (DRUV) confirmed the existence of two groups. The amorphous or crystalline nature of each sample tested by DRUV spectroscopy was independently verified by FT-Raman spectroscopy, differential scanning calorimetry, and X-ray diffraction.

The sample set of excipients was increased to include lactose, trehalose and raffinose. All experiments conducted with the saccharides were in agreement with each other. SEM of amorphous and crystalline trehalose with and without the probe showed that crystalline trehalose with phenol red has a very disrupted surface compared to amorphous trehalose with phenol red, or trehalose without phenol red. Other experiments showed that the original choice of concentration for phenol red was the optimum choice. A change in the wavelength in the DRUV spectra of any of the four saccharides used with phenol red was not observed with Reichardt’s dye.

A mechanism of action for perichromism (the change in wavelength observed) with phenol red is that perichromism occurs via hydrogen bonding, with potential changes to the planarity of the probe caused by different bonding mechanisms between the amorphous and crystalline surfaces. Perichromism is a quick, cheap technique that allows for a visual interpretation of morphological form of a pharmaceutical excipient, which could easily be adapted for use as an on-line pharmaceutical manufacturing test.

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