Polymorphism Screening

It has increasing importance in understanding and controlling the crystalline form produced. As a part of our pre-formulation development service, Creative Biolabs delivers polymorphism screening program to identify and characterize all relevant polymorphic forms, as well as their hydrates and solvates. We are able to precisely design experiments to understand the relationship between different solid phases. Our polymorphism screening strategy has been optimized by our highly expertized team through decades of experience and is readily tailored to our customers' needs.

Polymorphism is the ability for a single pharmaceutical entity to form two or more crystalline phases. Generally, there is only one desired active polymorph. The polymorph forms have severely impact on various physical characteristics (like drug stability). Therefore, it is critical to choose an optimum solid form to improve bioavailability. Besides, your product may not be thermodynamically stable in its current polymorphic form and may transform to another polymorph, which could lead to changes in physicochemical characteristics and even lead to rejection in IND-enabling process.

Creative Biolabs has the ability to screen and analyze different polymorphic forms of your active pharmaceutical ingredient (API). Our state-of-the-art X-Ray Powder Diffraction (XRPD), Differential Scanning Calorimetry (DSC) platform and several biophysical characterization studies (stability, dissolution, solubility, etc.) will deliver you with all the necessary data. Our services include:

Evaluate the Relative Thermodynamic Stability between Polymorphs

Identify polymorphs with the best physical stability and solubility plays a decisive role in determining the polymorphic form to be used in formulation. The thermodynamic stability can be experimentally determined by calculating different polymorphs' Gibbs free energy via direct heat capacity measurement, constructing the van Hoff's plot via solubility measurements, or by slurrying the mixtures of polymorphs over temperatures. Our capabilities including the following:

• Identify the thermodynamically stable polymorphic form and hydrates by front-line powder X-ray diffraction (PXRD) technology
• TGA and DSC to understand thermal behavior
• Chemical purity determination
• Hygroscopicity evaluation by GVS
• Optical microscopy or SEM to assess crystal habit
• Stability assessment

Figure 1 Energy/temperature diagrams of dimorphic systems (a) monotropic systems, (b) enantiotropic systems (Tp: transition point; Tf: fusion point; H: molar enthalpy; G: molar free energy; S: molar entropy; A, B: crystalline modifications; l; liquid phase). (Lee 2014)

High Throughput Methods

We provide automation and miniaturization method to obtain preliminary physicochemical characteristics using our robotic high-throughput screening instrument to form multiple crystalline forms. For every substance, we take into account solubility, possible chemical reactions and specific solvent-solute interactions, and help you choose the best solvents and solvent mixtures.

Amorphous Screens

In many cases, crystalline polymorphs do not allow for sufficient aqueous solubility. Amorphous form enables accurate and sensitive determination of API characteristics. Creative Biolabs has in-depth experience in inducing the amorphous forms of API which assures product quality and reliability.

After a few weeks and with less than 1 g of compound, Creative Biolabs guarantees a full polymorphism overview of your API. For more detailed information, please feel free to contact us or directly sent us an inquiry.

References

1. Lee E H (2014). “A practical guide to pharmaceutical polymorph screening & selection” Asian Journal of Pharmaceutical Science 9:163-175.
2. Hilfiker R, De Paul S M, and Szelagiewicz M (2006). “Approaches to polymorphism screening” Polymorphism: in the Pharmaceutical Industry: 287-308.

For Research Use Only.