Crystallisation Development of Drug Substances: Why is it Important?
The crystallisation process used to produce your new discovered therapeutic molecule defines the attributes of the solid isolated. Chemical purity, composition, crystallographic form, particle habit and size are the characteristics that can be controlled by the crystallisation used to generate the material. This operation produces API for evaluation in vitro, in vivo and also feeds the formulation development that culminates in the production of the drug product which the patient handles.
To help define the solid attributes isolated from the crystallisation process it would be advantageous to have an idea as to how the drug substance is to be administered; the dosage form. Oral dosage is ubiquitous, but other modes that are available include injectable, intravenous, pulmonary, dermal, nasal and buccal.
It is also beneficial to establish the aqueous solubility of the drug substance and where it falls within the Developability Classification System. The solubility can be determined as part of solid state investigations such as salt formation and propensity to polymorphism investigations, or during the discovery programme including the permeability of the newly identified compound.
The findings from chemistry, salt formation and polymorphism investigations provide the foundations which can drive the development of the crystallisation, in particular solvent chemotypes which can be delved into further. This then leads to identifying the process parameters which can be greatly aided by in silico modelling of the crystallisation process.
The solid produced by the crystallisation process must be defined by the chemical attributes of crystallographic form or salt version, water or solvent content and chemical impurity profile. The physical attributes of the solid - particle habit and size - can improve the flowability of the suspension, filtration and drying rates. These are particularly relevant as the overall process scale is increased and production assets changed.
By investing more in your drug substance early on during the investigations, save on unexpected delay on progressing your API into formulation, clinical evaluation and scale up.
Navigating solid state and crystallisation development of your newly discovered chemical entity can be daunting for small innovator organisations and where MorphCryst Consulting can support you in these activities from providing proposals and manage programmes to data review and appropriate recommendations.
