Solid form control of a drug substance: Ensuring robustness during scale-up

With the increasing prevalence for solubility limited drugs in R&D pipelines, there is in turn a greater level of attention given to optimizing and controlling the solid form. Whether it is to improve drug release in vivo or stability on the shelf, selecting the right polymorphic form can be critical to product performance. Alongside that is the protection of intellectual property rights brought about through crystal structure definitions in patent registrations. Hence, the solid form is typically specified in early development and maintained through to commercial production. The challenge then becomes in ensuring solid form control through scale-up, formulation and storage.

At Concept Life Sciences, we can take your drug substance from milligram to kilogram scale with reliable control of solid form. In this webinar, we describe how our Process R&D team in Chapel-en-le-Frith worked with our Analytical Scientists in Bradford, to develop a re-crystallization process for scale-up. Here, we discuss how we used the latest solid-state tools including the Crystal16 instrument of Technobis and Empyrean X-ray diffractometer of Malvern Panalytical to map the metastable zone and confirm polymorph purity. By doing so, we were able to improve yield and avoid uncontrolled secondary nucleation. The outcome was a more robust process to re-crystallize our client’s drug substance, up to 10’s of grams in scale.