XRPD is an important analytical technique for the characterization of small-molecule drugs, providing direct information about the state of an active pharmaceutical ingredient (API). XRPD patterns form an essential aspect of patent applications for new polymorphic forms.
This analytical technique is employed at various stages of drug development:
Studies of polymorphism and selection of the optimal form -, salt or co-crystal of the active ingredient, crystallographic identification of the polycrystalline structure, structure refinement and confirmation.
Development of a method to control polymorphism and crystallinity, support of crystallization scale-up, study compatibility and manufacturability- .
Investigation of crystalline state and polymorphic impurities of the API in both long-term and accelerated stability studies.
XRPD is used for quality control during the batch release of final drug products, as well as for control of the quality of raw materials - identity, purity, crystallinity and polymorphism.
Since XRPD patterns are directly related to the crystalline structure of a material, this is an ideal technique for the screening, identification and characterization of polymorphic forms and new chemical entities in API discovery and development. The XRPD pattern or crystal structure of a compound whether hydrate or solvate, is often important in securing a patent. The technique can also be used to provide key data to support regulatory submissions and new drug applications (NDAs). XRPD can be used to determine the crystallographic structure or identify the type and dimensions of the unit cell of crystalline pharmaceutical compounds. The most fundamental application of XRPD in drug development is in the identification and analysis of crystalline phases, such as polymorphs, hydrates and solvates.
The non-destructive nature of XRPD makes it a suitable technique for systematic preformulation studies and for testing drug-excipient compatibility. Excipient interactions are critical to the consistent release and bioavailability of the API. Developers must be able to fully understand and control this behavior to avoid potentially costly late stage problems caused by formulation instability. Development scientists looking to optimize formulations and drug release rely on XRPD data to screen for the polymorphs of a compound, quantify polymorphic impurities, determine crystallinity and assess crystallite size. XRPD also allows for the analysis of actual percentages of an API in the final dosage form, together with the percentages of any crystalline or amorphous excipients used. This technique can also detect potential solid-state transformations during tableting processes or arising from a compound’s hygroscopicity.
XRPD is used to monitor the quality of the finished drug product by determining the micro-structural parameters of the API and by detecting and quantifying the presence of pharmaceutical polymorphic contaminations. XRPD enables optimization of pharmaceutical process parameters and production control. It is used to assess the percentage of crystallinity and the morphology of active ingredients and fillers during manufacture. This is important since any change in the morphology of fillers or in the crystalline state of active ingredients in the final product can influence a drug’s solubility and bioavailability. XRPD can also be used to monitor batch/dosage uniformity and to ensure final product stability. GMP-compliant QC testing at DANNALAB is offered with a turnaround time of as little as 24 hours.