Improving apparent solubility: stabilizing the amorphous state

Since 2002, the Crystal16 has been installed in more than 300 laboratories around the world. Mainly used for solubility, crystallization, salt formation and co-crystal screening, the technology comes today with new applications. New demands and applications give assurance that the technology brought by this instrument is evolving continuously. Stabilizing the amorphous phase is one of the latest applications brought to our customers.

Some compounds just do not have the required solubility or dissolution rate and often they are killed in the development process for just these reasons. Amorphous materials are seen as a solution to this problem, because of their high energy state which gives rise to improved dissolution rates and apparent solubility. The big problem with amorphous materials, however, is that they are inherently unstable and tend to crystallize, thereby loosing these advantageous material properties. Amorphous solid dispersions are designed to overcome this problem by stabilizing the amorphous state of the active ingredient in a polymer matrix.

The Crystal16 offers an invaluable tool to automate the execution of amorphous solid dispersion screening, to quickly and effectively identify new solid dispersions of compounds. Amorphous solid dispersions screening may be performed with the Crystal16 in automated, controlled and flexible manner. The screening may take into account, for instance, the effect of drug loading (e.g. 5, 10, 15 and 25%), type of solvent (binary or ternary systems may be also considered), and temperature profile on the formation of solid dispersions. This way, a wide set of small-scale experiments using a minimal amount of compound can be performed. For example, in one run with the 16 reactors of the Crystal16, one can check the effect of two solvents, two drug loads and 4 polymers/excipients on the formation of solid dispersions for an active ingredient.

Additionally, the 16 reactors of the Crystal16 at a volume of 1 mL, enables scientists to determine solubility curves and critical solution temperatures. In-situ turbidity measurements can provide information about the apparent solubility and the dissolution rate of the various solid dispersions obtained.

For further information please check our publications database for the application note on "Improving apparent solubility: stabilizing the amorphous state" or the Crystal16 leaflet. Additionally, you may contact Technobis Crystallization Systems on +31 72 3020040 or info@crystallizationsystems.com.