Background

Many new and already existing drug molecules exhibit a low or almost non-existent solubility which can be a challenge when developing formulation and result in a product with low oral absorption. One way of improving the oral absorption is to use an amorphous form of the active substance, since this form has higher energy and speed of absorption compared to the crystalline equivalent. The crystalline form is defined through a specific three dimensional fixed structure, whereas the amorphous, in contrast, is defined by the lack of such a structure.

The most important aspect when developing an amorphous product is stability. This is because the amorphous form is thermodynamically unstable, meaning that amorphous products have a tendency to revert to a more stable, crystalline form during storage. This, in turn, could have a negative effect on the therapeutic qualities of the product. 

It is crucial for the Xspray business model that its products are completely amorphous without any crystalline elements. Therefore the company has used the most sensitive methods of analysis available today in order to ensure that its products are 100% amorphous. Ordinary X-ray based equipment is able to detect 5% or greater crystalline material in an amorphous sample, whereas Xspray’s equipment is able to detect 1% or greater. In addition, Xspray has investigated a sample of HyNap-Dasa which had been under storage for 20 months under a so called accelerated test of stability (40 oC and 75% humidity). The sample had been inside a synchrotron at MAXLAB in Lund where the radiation intensity enables 1000 times more sensitive analysis as to when compared to normal equipment. The test showed no signs of crystalline formations and the sample was considered to be 100% amorphous.

The most common technique when it comes to stabilizing an amorphous form is to include an excipient in order to create a so called solid dispersion which protects the active substance from crystallisation during storage. Even though this method has been known for several years, there are only a small number of formulations on the market that uses this principle which demonstrates the inherent difficulties with this formulation strategy.