Properties Associated with the Particulate Level

Particulate properties are defined as those material characteristics that effectively can be determined by the analysis of a relatively small ensemble of particles. Because the sample requirements for these assay methods are not extravagant, these properties often are also studied during early development once the drug substance is available in at least milligram quantities. 

Evaluation of the morphology of a pharmaceutical solid is of extreme importance, because this property exerts a significant influence over the micromeritic and bulk powder properties of the material.Microscopy is also useful as a means to obtain estimations of the particle size distribution in a powdered sample. A determination can be easily made regarding the relative crystallinity of the material, and skilled workers can deduce crystallographic information as well. Unknown particulates often can be identified solely based on their microscopic characteristics, although it is useful to obtain confirmatory support for these conclusions with the aid of microscopically assisted techniques. 

Both optical and electron microscopies are widely used to characterize pharmaceutical solids. Optical microscopy is limited to the range of magnification suitable for routine work, that is, an approximate upper limit of 600 X. However, this magnification limit does not preclude the investigation of most pharmaceutical materials, and the use of polarizing optics introduces a power into the technique that is not available with other methods. Electron microscopy work can be performed at extraordinarily high magnification lev- 

In another particularly interesting application, SEM analysis was used to study the growth of carbamazepine crystals on the surface of tablets that had been stored at elevated temperatures. This crystal growth was found to take place only when stearic acid was used as the tablet lubricant, and it was shown in this work that the carbamazepine drug substance could dissolve in 

The technique of x-ray diffraction is exceedingly important to pharmaceutics because it represents the primary method for obtaining fundamental structural information on crystalline substances. For example, it is only by pure coincidence that two compounds form crystals in which the three-dimensional spacing of planes is identical in all directions. One such example is provided by the trihydrate phases of ampicillin and amoxicillin, but such instances are uncommon. Typical applications of x-ray diffraction methodology include the determination of crystal structures, evaluation of polymorphism and solvate structures, evaluation of degrees of crystallinity, and the study of phase transitions. 

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A systematic approach to the physical characterization of pharmaceutical solids has been outlined [6], and it will be filled out in significantly more depth in the chapters of the present work. Within this system, physical properties are classified as being associated with the molecular level (those associated with individual molecules), the particulate level (those pertaining to individual solid particles), or the bulk level (those associated with an assembly of particulate species). 

Thus, the distinction between the hazard (an inherent toxic property of a chemical that may or may not be manifested, depending on exposure potential) and risk (the consequences of being exposed to a hazardous chemical at a particular exposure level) is critical (Purchase, 2000). Each component of a risk assessment—hazard identification, dose-response evaluation, and exposure assessment—is essential for evaluating the potential risks associated with the use of a substance such as a nanomaterial. The components of a risk assessment are universal in their application for assessing the hazards and risks of chemicals or products for a variety of industries or environmental exposures, regardless of the types of chemicals of interest (such as solvents, fibers, particulates and nanomaterials). 

Mechanical filtration systems are intended to limit the introduction of pollutants from outdoors to indoors. The efficiency of such systems generally depends on the filter properties and the aerodynamic properties of filtered particles [26]. The efficiency of filters varies from 5% to 40% for low-efficiency filters, such as dry media filters, panel and bag filters, from 60% to 90% for electrostatic precipitators to over 99% for high-efficiency particulate air filters. Not only the filters, but the whole heating, ventilation and air-conditioning system contributes to particle reduction, owing to particle losses on the cooling/heating coil and other parts of the system. The selection of a system depends on the type of indoor environment, outdoor and indoor sources, the demand on the level of reduction of pollutant concentrations and the cost associated with purchase, operation and maintenance of the system. 

Physical characterization can be performed at molecular, particulate, or bulk (macroscopic) levels. From the terminology cited by Brittain et al. (2), molecular properties are associated with individual molecules, particulate properties are considered as properties that pertain to individual solid particles, and bulk properties are those that are associated with an assembly of particulate species. Most reports in pharmaceutical literature cover characterization of bulk properties. 

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