1. Evaluation of cocrystal formation by solvent assisted grinding using
Automaxion adapter
Introduction: Although the field of cocrystals has generated huge interest in the
Pharmaceutical and Academic communities, the ability to predict, design and ultimately
prepare cocrystals is still at an early stage of development. As a result, unlike a typical salt
screen, it is very difficult to determine if any cocrystals of a selected API will successfully be
prepared and if they will display the desired physical and chemical characteristics.
In the last five years however there have been a growing number of publications that
reportedly describe new strategies for greatly increasing the likelihood of forming cocrystals.
In addition, a growing number of cocrystals of well understood drug molecules have now
been prepared that appear to display superior properties over the parent APIs.
Solvent assisted grinding is a widely used technique to generate cocrystals. A series of
experiments were carried out to evaluate the use of the Automaxion adapter using a Fritsch
milling system to generate new cocrystals for IP purposes.
Procedure: 28 coformers were carefully selected based on their predicted interactions they
could make with the studied molecule. Two solvents for grinding were selected based on the
partial solubility of the studied molecule in these solvents.
A mixture of the studied molecule (30 mg) and coformer (1.0 mol eq.) was placed in a
2 ml HPLC vial with two stainless steel beads (16 Stainless Steel Loose Ball Bearing - AISI
316 Stainless Steel - 3mm). The materials were initially wetted with 10 µl of EtOH or
acetonitrile and ground for 2 h at 650 rpm using a Fritsch milling system with Automaxion
adapter. Samples obtained after this grinding procedure were air dried for 5 min, and
analysed by XRPD.
Results: Based on the XRPD analyses, 2 cocrystals were identified from grinding with
EtOH. The same cocrystals and a new cocrystal were identified from grinding with
acetonitrile.
Conclusion: The Fritsch milling system with Automaxion adapter allows the parallel screen
of conditions for the cocrystal formation in a timely fashion with minimal amount of material
and good recovery.
Pharmorphix®
Preformulation Services
SAFC, through its Pharmorphix®
business, is a leading provider of solid form research
services to the pharmaceutical, biotechnology and specialty chemical industries. We focus on
understanding and optimising the physical and chemical properties of active ingredients and
formulated materials. For more information: www.safcglobal.com/pharmorphix