SR-XRPD Applications

X-Ray Powder Diffraction (XRPD) is ideal for the characterization of (bio)pharmaceuticals, supporting the Quality-by-Design (QbD) approach and the requirements of the new Food & Drugs Administration (FDA) guidance on process validation.

Pharmaceutical drug substances can exist in different crystalline forms (polymorphs), solvates/hydrated forms (pseudo-polymorphs) and amorphous forms, as a result of the manufacturing and storage conditions. These different forms can have a profound effect on the quality or performance (e.g. solubility, bioavailability, efficacy, safety) of the drug product [26-28]. For example, therapeutic failure has been attributed to uncontrolled hydrate formation in tablets during storage [29].

For this reason, it is now a regulatory requirement to conduct a detailed analysis of the polymorphism of the drug substance and drug product during technical development, including screening, characterization, property determination and setting of acceptance criteria for the different forms (see for instance the ICH Q6A guideline).

"The Gold Standard Technique"

To meet these requirements, XRPD, and even more so SR-XRPD, stands out as the gold standard technique [3,4]. It has thus become a key tool to support research, development, manufacturing and life-cycle management activities for (bio)pharmaceuticals.

Typical applications include

Structural solution of the solid form of new molecular entities during screening and selection processes
Development of formulation and screening of excipients, including co-crystals
Quality-by-design (QbD) approach for drug development
Characterization and high-accuracy quantification of all polymorphic forms in a drug substance and drug product, including in fully opaque blisters and in the presence of crystalline excipients.
Detection of impurities down to a trace level (< 0.05% wt)
Bi-dimensional distribution of drug substance polymorphs and excipients in a tablet
Optimization of manufacturing processes, in particular crystallization, formulation, drying, lyophilization, wet granulation, tabletting and packaging operations.
In situ non-ambient kinetic studies at milli-sec scale.
Stability studies of polymorphic forms
Continued Process Verification, in order to "maintain the process in a state of control over the life of the process" and "to continually improve [the] process", by performing "process improvement and innovation through sound science", as required by the new FDA guidance on process validation (FDA, 2011)
Comparability studies following process changes or technology transfers
Troubleshooting activities and investigations during commercial manufacturing
Patent application for new materials and patent-life extension
Detection of counterfeits even with minute differences

"Not only for pharmaceuticals"

SR-XRPD is a powerful technique in several other areas where the properties and performance of products are dependent on their crystalline structure and relative distribution of their polymorphic forms, such as:

Food and aroma compounds
Cosmetics
Pigments
Catalysts
Cement

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