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.
|PDF - Published Version |
Available under License Creative Commons Attribution Non-commercial No Derivatives.
Download (55MB) | Preview
It is important for the pharmaceutical industry to be able to distinguish between amorphous and crystalline material, as an unexpected change in crystallinity can affect the character, efficacy and even safety of a medicine. There are currently many techniques that are used to distinguish between morphological forms, but these have many drawbacks, including cost and limit of detection. In this context there are currently no techniques that can be adapted for on-line analysis.
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 under these conditions, visual inspection of the samples showed that there were two distinct groups. Each sample was analysed by diffuse reflectance ultraviolet spectroscopy (DRUV) spectroscopy which confirmed the existence of two groups. The amorphous or crystalline nature of each sample tested by DRUV spectroscopy was independently verified by the following techniques: FT-Raman spectroscopy; differential scanning calorimetry; and X-ray diffraction. These techniques were also used to compare the excipient without the probe to that with the probe molecule to ensure that the presence of the probe molecule had not affected the sucrose.
Once the experimentation had been concluded using sucrose as the pharmaceutical excipient, the sample set of excipients was increased to include lactose, trehalose and raffmose. All experiments conducted with the saccharides were in agreement with each other. SEM of amorphous and crystalline trehalose with and without the probe was also performed, which 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 were conducted into probe choice and concentration, showing that the original choice of concentration for phenol red was the optimum choice. Reichardt's dye was chosen as a comparison probe to phenol red as Reichardt's dye is the most solvatochromic probe so far discovered. Reichardt's dye has very poor aqueous solubility, necessitating a change in method, so a rotary evaporator was used. 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. DSC was used to confirm that each saccharide with Reichardt's dye had been made amorphous or crystalline.
A mechanism of action for perichromism (the change in wavelength observed) with phenol red is suggested, and that 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. These studies show that 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.
|Item Type:||Thesis (PhD)|
|Uncontrolled Keywords:||amorphous, crystalline, DRUV spectroscopy, ultraviolet-visible spectroscopy, perichromism, diffuse reflection spectroscopy, DRS|
|Subjects:||Q Science > Q Science (General)|
Q Science > QD Chemistry
|School / Department / Research Groups:||School of Science|
School of Science > Department of Pharmaceutical, Chemical & Environmental Sciences
|Last Modified:||10 Dec 2013 16:07|
Actions (login required)