Onyx has developed a customised approach towards providing high-throughput polymorph screening services. The polymorph screening process utilises a 96 well plate work flow system, delivering maximum efficiency whilst maintaining exceptional resolution and is capable of rapidly performing a large number of experiments on milligram amounts of target material.
We have a dedicated solid state research team with a wealth of expertise in polymorphism and crystallisation problem solving, gained through various internal and external projects. It is well recognized that X-ray powder diffraction is one of the best methods to discriminate solid polymorphism forms and as such; transmission X-ray powder diffraction is used as the primary tool to identify and differentiate pure and mixed polymorphic forms. Data quality is further enhanced by the use of the latest 2-Dimensional detectors for X-ray powder diffraction.
In combination with X-ray diffraction our approach also utilises state of the art, high throughput Raman spectroscopy. The combined data streams are then analysed using cheminformatics software, delivering a unique polymorph screening methodology that enhances understanding of the polymorphic behaviour.
The ultimate goal of any investigation undertaken at Onyx is to provide support in choosing the optimal crystal form commensurate with project objectives. Projects are therefore flexible and accommodate specific customer requirements. As a guide, however, the following are typical work programs:
Mini Screen
An ideal polymorph screening where the amount of material is limited (100-300 mg) and budget is a limiting factor. The polymorphism screen is focussed on selecting a limited number of solvents from a given experimental design space, in this way maximizing the opportunities for identifying new polymorphic forms whilst recognizing there could be a need for solvent change later. Additional material is required for further polymorphism characterisation relative to stability and solubility.
Standard Screen
Our standard polymorphism screening is designed to identify as many of the solid forms of your drug substance as possible during a fixed period. We also scale up each different polymorphic form that is deemed suitable for progression via selection criteria, characterise each analytically, and determine relative stabilities (thermal analysis and GVS) and solubility’s in order to allow polymorphism form selection and to provide a defendable IP polymorphism position. This would then lead into a subsequent scale-up and development exercise geared towards producing targeted polymorphic form material suitable for manufacture in a GMP environment. Our wealth of experience in crystallisation and process development is a key benefit here.
Macro Screen
This is a complete polymorphism screening with a wider range of solvents (more than 100). The use of various technologies (automated Zinsser Crissy platform, XRPD, Raman spectroscopy and others) in combination with appropriate computational techniques gives us an exceptional ability to explore and find the useful polymorphic forms of a drug substance. We have designed experiments that cover a wide range of physical conditions and techniques in order to generate as many new solid polymorphic forms as possible. A comprehensive set of analytical techniques would be applied during this screen, as appropriate, in order to systematically characterise all new polymorphic forms identified. The emphasis of this screen is to provide a complete basis for IP coverage and polymorph reporting in a New Drug Application to the USFDA or equivalent to other national authorities.
