However, the propensity for re-crystallisation may be exploited to an advantage in the formulation of freeze-dried rapidly disintegrating tablets (RDTs) to enhance the mechanical properties without impacting the disintegration profile ( 2, 3).ĭifferent techniques such as thermal analysis, X-ray diffraction (XRD), powder X-ray diffraction (PXRD), and a number of optical spectroscopies have been used to study crystallinity in pharmaceutical formulations. For instance, when certain amorphous sugars, such as sucrose, are humidified following freeze drying, the amorphous sugar is fully or partially converted to the crystalline form ( 1). An increase in the crystalline component of a drug substance will slow the dissolution rate which could then impact bioavailability. crystallise from the amorphous state) under poor storage conditions, inappropriate packaging, or further processing. The amorphous state of any material is always thermodynamically less stable than crystalline state and hence the material may devitrify (i.e. The control of the amorphous and crystalline states of drugs and excipients is important in many instances of product formulation, manufacture, and packaging, such as the formulation of certain (freeze-dried) oral disintegrating tablets (ODTs), the size reduction of powders by micronisation process, and the ingress of moisture through the packaging material during storage. The quality and stability of the pharmaceutical product is frequently dictated by the physical state of the ingredients, such as the polymorphic form of the drug, the hydration state of an excipient, and the proportion of crystalline and amorphous phases of each component. The potential for using THz spectroscopy, as a quantitative in-line tool for percent crystallinity in a range of complex systems such as conventional tablets and freeze-dried formulations, is suggested in this study. Calibration models were constructed based on (1) peak area analysis and (2) partial least square regression analysis, with the latter giving the best LOD and LOQ of 0.76% and 2.3%, respectively. The THz spectra of crystalline sucrose showed distinct absorption bands at ∼48, ∼55, and ∼60 cm −1 while all these features were absent in the amorphous sucrose. The terahertz spectrum of sucrose was recorded in the wave number range between 3 and 100 cm −1 for both the pure crystalline form and for a mixture of the crystalline and amorphous (freeze-dried) form. This study examines the use of terahertz-pulsed spectroscopy (TPS) coupled with two different data analytical methods as an off-line tool (in the first instance) for assessing the degree of crystallinity in a binary mixture of amorphous and polycrystalline sucrose. The control of the amorphous and crystalline states of drugs and excipients is important in many instances of product formulation, manufacture, and packaging, such as the formulation of certain (freeze-dried) fast melt tablets.

Optimage polycrystalline powder