Polymorphism Screening

Polymorphism is central to gaining FDA approval of an NDA. It is critical that an optimum solid form is chosen for manufacture as the polymorphic form can have severe implications on physical characteristics such as 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 our clients’ needs and to find the other polymorphs for IP protection.

What is Polymorphism?

Polymorphism is the ability for a single chemical entity to form two or more crystalline phases. Many APIs exhibit several polymorphic forms and in many cases there is only one desired polymorph, which is decided upon by numerous factors discussed below. According to statistics at least 80% of organic substances form two or more polymorphs.

Why is it important to perform Polymorphic Screening?

There are important reasons for performing a Polymorphic screen of your API.

i)	Polymorphs have different physico-chemical properties such as solubility, dissolution rate and melting point which influence their biological activity, pharmacodynamic properties and stability. Therefore, polymorphic forms of API are considered by drug authorities (FDA, EPA) to be different entities.
ii)	Your product may not be thermodynamically stable in it’s 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.
iii)	Polymorphic forms are the subject of IP protection. If you are the originator of the API, you would not only want to find the most suitable form for use, but also protect your API by IP to avoid competition form Generic companies.
iv)	If you are a generic company, your goal is to try to find a useable polymorphic form which is not protected by the originator’s IP.

Amorphous Screens

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 API.

Dalton Pharma Services have the in-depth knowledge and experience to perform exhaustive polymorph screenings 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) etc. XRPD will be applied as the initial study of the polymorphic form followed by DSC, FTIR, mp, normal time 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 to induce into your API drug substance.