Polymorphism is the ability for a single chemical entity to form two or more crystalline phases. Having a clear understanding of the polymorphism of your product is central to gaining US FDA approval of your NDA. It is critical that an optimum solid form is chosen for manufacture since the polymorphic form can severely impact physical characteristics resulting in lower Bioavailability.
Dalton Pharma Services can perform screening of polymorphic forms for any API of interest via state of the art analysis including DSC, XRPD, FTIR and dissolution/solubility testing to determine the best polymorphic form for your product. Dalton can also identify additional polymorphs for IP protection purposes, supporting your filing.
Many APIs exhibit several polymorphic forms and in many cases there is only one desired polymorph.
Performing Polymorphic Screening is critical because:
i) Polymorphs have different physico-chemical properties such as solubility, dissolution rate and melting point which influence their biological activity, pharmaco-dynamic properties and stability. Therefore, polymorphic forms of an API are considered to be different chemical entities by drug regulators.
ii) Your product may not be thermodynamically stable in its current polymorphic form and during formulation of the drug product or during storage it may transform to another polymorph, which could lead to rejection of the API or dosage form product.
iii) Polymorphic forms are subject to IP protection. Innovator companies identify polymorphs in the active pharmaceutical ingredient (API) to protect the associate IP related to a new API and thus avoid premature competition from generic companies.
iv) Generic companies try to identify usable polymorphic forms of drugs that are not restricted by innovator patents, so that they can launch a non-infringing generic version of the product.
In many cases crystalline polymorphs do not allow for sufficient aqueous solubility and the amorphous form may be required. Dalton has in-depth experience in the numerous techniques used to induce the amorphous forms of active pharmaceutical ingredient.
Dalton Pharma Services has the in-depth knowledge and experience to perform exhaustive polymorphic screening for you. A typical screen will consist of the analysis of different forms induced by solvent type, slow and fast evaporation, slow and fast crystallization, thermal, and physical (grinding). XRPD will typically be applied to initially study of the polymorphic form followed by DSC, FTIR, Melting Point, normal and accelerated stability, dissolution and solubility studies to provide you with all the necessary data so you can make an informed decision as to which polymorph you desire for your API drug substance.