X-ray diffraction or XRD has shown a huge potential in new drug development, manufacturing and quality control of manufactured pharmaceutical formulations. The greatest asset of the XRD technique is its non-destructive nature and therefore the sample is available for further analytical confirmations.
Pharmaceutical formulations are available as tablets, capsules, syrups, injectables, creams, lotions, aerosol sprays, etc X-ray diffraction provides valuable information on polymorphism, degree of crystallinity and amorphous character of solid formulations. In other words it is an ideal fingerprinting technique for such formulations.
The present article discusses some common applications of the technique during stages from drug development to manufacture of finished products.
A pharmaceutical formulation is a complex mixture of several compounds which comprise of the active drug ingredient together with other ingredients called excipients which act as fillers, binders, lubricants, colourants, sweeteners, disintergators, etc to achieve the desired properties of a dosage form. The presence of a multitude of materials adds to the complexity of the formulation and a research scientist has to try out various permutations and combinations before the formulation is approved for commercialization.
XRD is certainly is helpful to the development chemist as it provides valuable details on degree of crystallinity and amorphous content of synthetic mixtures. Crystalline impurities present can be quantified down to 0.05% levels.
XRD data is accepted for new product registrations and patent applications. Single crystal structure of the active ingredient and powder pattern of the finished formulation are essential prerequisites for registration of new patents.
The development chemist has to collect important details on the following parameters before a product moves from laboratory to the manufacturing unit.
Crystal structure – the lattice type and dimensions of a unit cell need to be specified for the crystalline content
Polymorphism -polymorphic content can impact properties such as solubility and dissolution rate, bioavailability and stability so it is important to collect details on polymorphic properties of ingredients of a drug material
Percentage of crystallinity – the percent crystallinity is a valuable parameter for drug dosage form. It has significant influence on manufacturing and processing as well as the pharmacological behaviour.
Compatibility with excipients-XRD makes it an ideal choice for studies on active drug- excipient combinations. A detailed study of the chosen excipients with active pharmaceutical ingredient is a must for consistency of properties such as drug release and bio- availability
Manufacturing process control
Manufacturing process can involve morphological changes in crystalline phase due to introduction of stress forces. Such changes can influence a drug’s bioavailability
The nondestructive nature of XRD analysis makes it an ideal choice to fix the safe tableting pressure range so that the dosage form achieves its targeted dissolution rate and bio availability.
With its diverse range of applications XRD is gaining a high degree of popularity in pharmaceutical manufacturing and quality certifying laboratories.