Pharmaceutical solids bulk characterization

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). 

The topics of polymorphism and pseudopolymorphism dominate the majority of publications that deal with utilizing infrared spectroscopy for the physical characterization of pharmaceutical solids. Typically, in each of the publications, IR spectroscopy is only one technique used to characterize the various physical forms. It is important to realize that a multidisciplinary approach must be taken for the complete physical characterization of a pharmaceutical solid. Besides polymorphism, mid- and near-IR have been utilized for identity testing at the bulk and formulated product level, contaminant analysis, and drug-excipient interactions. A number of these applications will be highlighted within the next few sections. 

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. 

Solidification of the particles may not be the final step in the formation process of solid lipid particles. Lipidic materials exhibit rich polymorphism [69,70], which may also occur in the dispersed state. In nanoparticles, the polymorphic behavior of the matrix lipids may, however, differ distinctly from that in the bulk material. Polymorphic transitions are usually accelerated in the nanoparticles compared with the bulk lipids [2,62]. In some cases, polymorphic forms not observable in the corresponding bulk materials were detected in lipid nanoparticles [1,65]. Because polymorphism can affect pharmaceutically relevant properties of the particles, such as the drug incorporation capacity [65], corresponding investigations should also be included in the characterization process. As long as polymorphic or other crystalaging phenomena have not terminated, the particle matrix cannot be regarded as static, and alterations of the particle properties may still occur. 

Bryan J. Ennis, Ph.D. President, EirG Associates, Inc., and CEO, iPowder Systems, Inc. Co-Founder and Member, Particle Technology Forum, American Institute of Chemical Engineers Member, American Association of Pharmaceutical Scientists (Section Editor, Bulk Flow Characterization, Solids Handling, Size Enlargement)... 

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