Solid form

Polycrystalline type (polymorphism) refers to: some material with the same chemical composition, but because of the different molecular arrangement, and in more than one crystal form phenomenon.To many technical areas (especially for the pharmaceutical industry), to identify, parsing, and regulate a polycrystalline material form, is of vital importance.

Most drugs come in a solid form of medication (such as tablet, capsule and inhaled materials), and active pharmaceutical ingredient (API) polymorphic forms especially noteworthy, because it can influence the solubility of drug in the body, and then change the bioavailability.

In addition, the active ingredient of polycrystalline morphology will process, formula and the influence of storage conditions.So in the active pharmaceutical ingredient synthetic route development, formulation development, storage and manufacturing process, such as type of polycrystalline testing is necessary.

Due to a kind of active pharmaceutical ingredient may also have a number of different polymorphic forms, so technically very difficult to achieve in a particular sample, determine the types of polymorphic forms of combinations of several forms.May be there are other important material in the sample (e.g., solvate, hydrate and amorphous content).These substances can affect the overall judgment, the measuring difficulty will rise further.Therefore, the industry typically use a variety of characterization methods to solve this difficult problem.

Brooke provide four leading technology (X ray diffraction, NMR spectroscopy, Raman and MIR spectra).Height between these methods complement each other, and belong to the development of mature technology, itself has the advantages of rich information, nondestructive, and each test only a small amount of samples (tens to hundreds of mg).

X-ray diffraction technology in drug life cycle stages of characterization of polycrystalline model plays a key role.Both known and new phase, all can be tested by powder X-ray diffraction (PXRD) and identification (i.e., "fingerprint").Once recognition, can be applied to the crystal and amorphous material sample to phase quantitative analysis.Single crystal X-ray diffraction (SC - XRD) and PXRD to ab initio crystal structure determination.Compared with the PXRD, SC - XRD results more clear, is the first choice for structure characterization.SC - is the most important of XRD to determine the absolute structure of molecules, so as to distinguish between enantiomorphism isomers.In the case of unable to grow single crystal (SC - XRD no longer apply), PXRD highlights its important role in the structure characterization of because it can pass the analytical structure for medicine powder sample.

Solid state nuclear magnetic resonance spectrum (SSNMR) is an excellent complement analysis technology, can be used to solid medicine for structural characterization of active pharmaceutical ingredients and finished products.It has multiple purposes, for example, by solid state nuclear magnetic resonance spectrum to identify different crystal and/or functional form of transformation in the process of monitoring the active pharmaceutical ingredient amplification, detection of other trace form (such as the crystal in a functional, determination of thermal relaxation time in order to predict chemical stability, and protect intellectual property rights.Similarly, solid-state nuclear magnetic resonance (NMR) technology is particularly suitable for characterizing the finished medicine, because the excipient usually do not cause significant interference to pharmaceutical analysis, even if in the finished product drug API content is low.

When samples contain both crystal and/or excipient and amorphous content, time domain (TD - NMR) nuclear magnetic resonance spectrum can be effective quantitative analysis of amorphous material.Even amorphous content is very low, TD - NMR also has a very high accuracy.TD - NMR is a nondestructive testing technique, namely the samples after the measurement is still intact.TD - NMR can also be used to measure samples in the container directly.In addition, similar to other desktop instrument, TD - NMR is easy to use, low cost, cover an area of an area small, and many other advantages.

Raman spectroscopy can fast reliable region of different type polycrystalline, therefore is widely used in characterization of solid materials.By using Raman microscopy imaging technology, which can determine the drug, such as tablets, etc.) in a polycrystalline model of space distribution, and identify pollutants at the same time.The technology also can be used to study under the condition of high temperature and high pressure, the transition between different forms of polycrystalline.In addition, the handheld device and high flux (HTS) options for routine quality control provides a powerful solution.

In the infrared spectrum (MIR) is a conventional method, is used to identify chemicals.In the far infrared (FIR) spectral range, by detecting the primary chains in the lattice vibration to distinguish different type polycrystalline.Brooke introduced intelligent FTIR spectrometer, it adopted a unique frequency modulation technology, a rapid measurement of complete FIR - MIR spectra range, and can be used to identify the samples at the same time and polycrystalline type filter.Due to pick up the most advanced diamond attenuated total reflection (ATR) accessory, brooke FTIR spectrometer to measure the need for sample preparation, which greatly simplifies the drug research and development and production of daily work.