Methods to Identify and Analyze Drug Crystal Form
SummaryThe pursuit of "advantageous drug crystal form" has become the focus of current drug crystal form research.
- Author Name: Lisa George
Ever since the discovery of the two crystal forms of benzamide in the 18th century, scientists have been searching for the "superior drug crystal form" of innovative drugs. Obviously, crystal form research has become an important part of the drug development process. From a technical perspective, the research of drug crystal forms can play a role in ensuring the quality of drugs. The solid state of the dominant drug can have one or more crystal forms, so one crystal form or a mixed state can be selected as the medicinal crystal form. The pursuit of "advantageous drug crystal form" has become the focus of current drug crystal form research. Then how can the crystal form of the drug be identified and analyzed?
There are currently a variety of methods to quantitatively and qualitatively analyze and identify drug crystal forms, and qualitative identification accounts for a relatively large proportion in pharmaceutical research. The currently mature methods being used mainly include XRD, DSC, TGA, IR, RM, etc.
Single crystal X-ray diffraction method (SXRD)
SXRD is a non-destructive analytical technique, which provides detailed information about the internal lattice of crystalline substances, including the composition of the test product (compound, crystal water or solvent), unit cell parameters (a, b, c, α, β, γ, V), molecular symmetry (crystal system , Space group), molecular bond and mode (hydrogen bond, salt bond, coordination bond), molecular conformation and other parameter changes. The method is suitable for the identification of crystalline substances.
Powder X-ray diffraction method (PXRD)
In the identification of crystal forms, the number, position, intensity (relative or absolute) of the diffraction peaks of the test product, and the ratio of each peak intensity are used to identify the state of the crystalline material. The method is suitable for the identification of various crystalline substances such as crystalline state and amorphous state, amorphous state and amorphous state. If the crystalline material states of the two crystalline samples are the same, then the following requirements should be satisfied: the number of diffraction peaks is the same, the error range of the two 2θvalues of the diffraction peak position is within ±0.2°, the relative peak intensity error of the diffraction peak at the same position is within ±5% , and the order of the intensity of the diffraction peaks should be consistent. If the crystalline material states of the two amorphous samples are the same, the geometric topological shape of the dispersion diffraction peaks should be completely consistent.
Differential Scanning Calorimetry (DSC)
Utilizing the unique thermodynamic properties of the different crystalline substances of the test product, the change of the number, position, shape, endothermic heat (or endothermic enthalpy) and other parameters of the test product's endothermic peak or exothermic peak is used to identify the state of the crystalline substance. The method is suitable for the identification of the melting endothermic peaks of different crystalline substances with large differences or the test product containing different amounts and types of crystalline solvents (or water).
This technique utilizes the unique mass-weight loss percentage and temperature relationship parameter changes of the different crystal types of the test product to identify the state of the crystalline substances. TG is suitable for the identification of crystalline substances containing different amounts and types of crystalline solvents (or water).
Infrared spectroscopy (IR)
This technique utilizes the unique dipole moment changes when the molecules of different crystalline substances of the test sample are vibrated to cause parameter changes such as the position, intensity, and geometric topology of the infrared spectrum absorption peak in the specified wavelength range to realize the identification of the state of the crystalline substance. The method is suitable for the identification of crystalline substances with varying molecular forces. The attenuated total reflection sampling method is recommended for the identification of crystalline substances. When preparing samples, attention should be paid to avoiding the phenomenon of crystal conversion caused by grinding and pressing.
Raman Spectroscopy (RM)
This technique uses the unique molecular polarizability changes of the different crystalline substances to change the position, intensity, and geometric topology of the Raman spectrum absorption peak in the specified wavelength range so as to realize the identification of the state of the crystalline substance.