Grinding pharmaceutical materials

Keywords Solid-state grinding Cocrystal formation Crystal engineering Pharmaceutical materials Polymorphism... 

The basis for reactivity in the solid state lies in molecular mobility and molecular complementarity. Grinding is well known to create lattice defects and amorphous phases,and the formation of polymorphic forms of drugs as a result of these stresses is well documented in the pharmaceutical literature. Therefore, the concepts of solid-state reactivity in pharmaceutical materials can be applied to understanding the formation of cocrystals. 

Schoenmakers et al. [72] analyzed two representative commercial rubbers by gas chromatography-mass spectrometry (GC-MS) and detected more than 100 different compounds. The rubbers, mixtures of isobutylene and isoprene, were analyzed after being cryogenically grinded and submitted to two different extraction procedures a Sohxlet extraction with a series of solvents and a static-headspace extraction, which entailed placing the sample in a 20-mL sealed vial in an oven at 110°C for 5,20, or 50 min. Although these are not the conditions to which pharmaceutical products are submitted, the results may give an idea of which compounds could be expected from these materials. Residual monomers, isobutylene in the dimeric or tetrameric form, and compounds derived from the scission of the polymeric chain were found in the extracts. Table 32 presents an overview of the nature of the compounds identified in the headspace and Soxhlet extracts of the polymers. While the liquid-phase extraction was able to extract less volatile compounds, the headspace technique was able to show the presence of compounds with low molecular mass... 

There are practical problems associated with many of the above processes for example, there are many materials that are difficult to process by grinding or solution techniques for one reason or another. Certain dyes, chemical intermediates, biological and pharmaceutical compounds which are "waxy" or "soft , certain specialty polymers, and explosives are a few categories of difficult to process materials. 

Investigation of the role that liquid media play in the intensification of the grinding of solid materials is one of the main subjects of physico-chemical mechanics described in Chapter IX. The role of surfactants is equally important in the emulsification and foaming of liquids, which are processes broadly used in various technologies across the chemical, pharmaceutical, and food industries. 

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