Drug substances solid-state analysis

Discovery of NCE and high-throughput screening Solid-state analysis of drug substances Degradation and impurity analysis of drug substances Preformulation analysis... 

Solid-state analysis - this is probably the most common application of vibrational spectroscopy and includes both drug substance and product. 

As was the case with solid-state analysis, it is convenient to make a distinction between early and late stage development. In early stage development, generally there is little drug substance available and crystallization conditions have not been optimized. Particle evaluations using optical and scanning electron... 

Solid-state samples can be prepared by accurately weighing the drug substance into a container that can be stored under the appropriate condition. Suitable containers include volumetric flasks, scintillation vials, etc. The amount of drug substance used is usually dictated by the availability of material, accuracy of balances, and the final concentration desired for analysis. Typical amounts used for solid-state samples would be between 2 and... 

Polymorphism is customarily monitored by melting point or infrared spectral analysis. However, other methods, such as X-ray diffraction, thermal analytical, and solid-state Raman spectroscopy, also can be used. It is expected that the sponsor will conduct a diligent search by evaluating the drug substance recrystallized from various solvents with different properties. Either the basis for concluding that only one crystalline form exists, or comparative information regarding the respective solubilities, dissolution rates, and physical/chemical stability of each crystalline form should be provided. 

Regarding production of bulk drug substances, specifications for contaminants should be established for all solvents used in the process. A comparison should be performed between the manufacturer s Certificate of Analysis and the submitted specifications, and any discrepancies should be justified. A full description for the route of synthesis should be given, as this is important for the testing and control of impurities and process solvent residues. The FDA expects that, at the time of submission, it will be determined if the drug substance exists in a multiple solid state form (racemic mixture stereoisomer) and whether this affects the dissolution and bioavailability of the drug product. 

The pharmaceutical analysis of finished solid oral dosage forms is discussed in Chapter 6 from the standpoint of what makes this type of delivery form unique and successful (i.e., the physical properties and the state of the drug substance... 

This chapter has presented a survey of some of the ways that microscopy can aid in the development of pharmaceuticals. Microscopy can make important contributions to the solid-state characterization of the drug substance, to particle size analysis, and to contaminant identification. It is often joked, though, that the most important instrument in microscopy lies just above the eyepieces - a skilled, well-trained microscopist. It is no joke that the techniques described in... 

Supercritical phase extraction is the chosen method for extracting drugs, including opiates, cocaine, and methadone from a solid matrix such as hair. In its present state, supercritical phase extraction can be used with these three groups of drugs. In the near future, however, it is probable that this method will be applicable to other drugs and even to other medical substances. At that time, SFE will probably become the reference method for hair analysis. 

Identification and characterization of the structures of unknown substances are an important part of organic chemistry. It is often, of necessity, a micro process, e.g., in drug analyses. It is sometimes possible to establish the structure of a compound on the basis of spectra alone (ir, uv, and nmr), but these spectra must usually be supplemented with other information about the unknown physical state, elementary analysis, solubility, and confirmatory tests for functional groups. Conversion of the unknown to a solid derivative of known melting point will often provide final confirmation of structure. 

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