Evaluation of different screening methods to understand the dissolution behaviors of amorphous solid dispersions

The objectives of the current study were to understand the dissolution behaviors of amorphous solid dispersions (ASD) using different screening methods and their correlation to the dissolution of formulated products.

A poorly soluble compound, compound E, was used as a model compound. ASDs were prepared with HPMC, Kollidon VA64 and Eudragit EPO using hot-melt extrusion. Different techniques including precipitation, powder, capsule and compact dissolution and the dissolution of formulated products were conducted in USP simulated gastric fluid using a USP II dissolution apparatus.

It was found that a precipitation study could generally predict powder, capsule and compact dissolution. Yet, it was recommended to run the dissolution at a higher paddle speed or for a longer duration to improve the predictability. It was also recommended to run powder, capsule and compact dissolution at both slow and high speeds to gain insights into wetting, dispersion and the dissolution of a system. Sometimes, capsule or compact dissolution could not be predicted by precipitation or powder dissolution due to plug formation. In this case, properly designed dosage forms were needed to break up this plug to optimize the dissolution profiles. On the contrary, formulations and dissolution conditions would have minimal effects on the dissolution profiles of a fast-dissolving solid dispersion.

Different techniques are available to select the right polymers to optimize dissolution behaviors. However, it is important to understand the merits and limitations of each technique in order to optimize the formulations for amorphous solid dispersions.