Investigation of Polymorphic Transformations Using Raman Chemical Imaging & Differential Scanning Calorimetry

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Polymorphs are chemicals of identical molecular structure with different crystal lattice formations. Screening for polymorphs is crucial for drug research and development since the crystal form of the active pharmaceutical ingredient (API) directly correlates with its pharmacokinetic properties. Additional property differences among polymorphs include: solubility, stability, dissolution rate, miscibility and excipient compatibility in the final formulation. Polymorph transition or creation is often unwanted and occur due to uncontrolled parameters like the presence of impurities or temperature and/or solvent- induced rapid transitions. Ultimately, polymorph conversion or unintended formation of hydrates, solvates or salts affects the bioavailability of an API in the final formulation.

Crystallization and preservation of a specific polymorph form is the key challenge for drug researchers and developers. Thermodynamic stability directly affects polymorphic crystallization and can be induced by nucleation or in response to external parameters such as temperature, pressure, meltmediation and solution-mediation. Understanding phase transition mechanisms that define polymorph-dependent nucleation is crucial for manufacturing and stabilizing drug compounds especially when polymorphic transformations easily occur. In-situ analytical methods are employed to understand nucleation processes that manifest metastable or amorphous forms that may not be easily isolated for X-ray diffraction analysis.

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David Exline has more than 20 years of experience in managing and administering analytical laboratory and consulting services. As President of Gateway Analytical, he oversees the company’s day-to-day operations, business growth and service areas.