Particle size characterization, pharmaceutical

Sensors for particle size characterization used for crystallization include ultrasound attenuation measurement/ " laser diffraction/ and laser backscatteiing/ commercially called focused beam reflectance measurement (FBRM). Ultrasonic attenuation spectroscopy has been used to monitor the crystallization process parameters such as the crystal size distribution, concentration, and the onset of nucleation during batch crystallization of L-glutamic acid/ Off-line laser diffraction has been used to measure the crystal size distribution in the development of the crystallization process for a pharmaceutical intermediate/ ... 

Crystallization General Principles and Significance on Product Development, p. 834. Particle-Size Characterization, p. 2582. Polymorphism Pharmaceutical Aspects, p. 2935. Spectroscopic Methods of Analysis Infrared Spectroscopy, p. 3405. 

A reappraisal of the particle size characterization of pharmaceutically relevant materials, including therapeutic aerosols, was advocated in the late 1980s [1], This led to a reevaluation of compendial standards for particle size measurement [2], By the late 1990s most pharmacopoeia had adopted new standards for the testing of inhalation aerosols. 

There has been significant research in the area of particle size characterization of pharmaceutical aerosols since the early 1990s. The focus has been not only on methods but on data presentation, analysis, and requirements for regulatory submissions. 

In the pharmaceutical industry, surface area is becoming more important in the characterization of materials during development, formulation, and manufacturing. The surface area of a solid material provides information about the void spaces on the surfaces of individual particles or aggregates of particles [5], This becomes important because factors such as chemical activity, adsorption, dissolution, and bioavailability of the drug may depend on the surface on the solid [3,5]. Handling properties of materials, such as flowability of a powder, can also be related to particle size and surface area [4],... 

A wide range of physical constants, for instance melting point, boiling point, specific gravity, viscosity, refractive index, solubility, polymorphic forms vis-a-vis particle size, in addition to characteristic absorption features and optical rotation play a vital role in characterization of pharmaceutical chemicals and drug substances. These physical constants will be discussed briefly with typical examples as under ... 

The equation of Heckel has been discussed again and again. One main issue of critique is that pharmaceutical powders are not purely plastically deforming materials and thus particle size and deformation mechanisms influence the derived parameters [129, 130]. Already very small errors in displacement determination or the measurement of true density can induce huge errors in the derived parameters [75-77, 129, 131, 132], Spnnergaard [126] referred the equation of Walker and Bal shin for his characterization of materials. He criticized further that the yield strength derived from the Heckel equation is directly dependent on the true density of the powders [127]. 

The importance of size reduction in relation to pharmaceutical active agents and excipients is well known, and the aim of this chapter is to identify methods for particle size reduction, discuss how particle size and shape are characterized, and... 

Particle behavior is a function of particle size, density, surface area, and shape. These interact in a complex manner to give the total particle behavior pattern [28], The shape of a particle is probably the most difficult characteristic to be determined because there is such diversity in relation to particle shape. However, particle shape is a fundamental factor in powder characterization that will influence important properties such as bulk density, permeability, flowability, coatablility, particle packing arrangements, attrition, and cohesion [33-36], Consequently it is pertinent to the successful manipulation of pharmaceutical powders that an accurate definition of particle shape is obtained prior to powder processing. 

MDI products are subject to batch control and acceptance tests similar to those for other pharmaceutical dosage forms, that is, active drug identification, dose delivery, and dose uniformity. Additional special tests unique to inhalers, e.g., characterizing the particle size distribution of the delivered aerosol, are also applied. Typical tests are shown in Table 3. 

An advantage of equivalent diameters is that they provide a unique characterization of particle size for the given method of measurement. In addition, the diameter gives information about the particle properties. For example, the equivalent surface diameter would give information about the surface area of the particle and the equivalent volume diameter would give information about the volume. Thus, if the density of the particles is known, the mass and properties important to pharmaceutical applications can be calculated. The numerical value for equivalent diameters derived from different geometric properties will only be identical in the case of perfectly spherical particles, and if the particle irregularity increases so will the differences between the different equivalent diameters. 

A wide variety of methods have been used to measure the particle size of aerosols, and most of these have found an application in the specialized field of pharmaceutical product characterization. In general, these approaches result in the measurement of a particular diameter that may be defined according to the principle underlying the measurement [3]. 

Numerous methods are required to characterize drug substances and drug products (Chapter 10). Specifications may include description identification assay (of composite sample) tests for organic synthetic process impurities, inorganic impurities, degradation products, residual solvents, and container extractables tests of various physicochemical properties, chiral purity, water content, content uniformity, and antioxidant and antimicrobial preservative content microbial tests dissolution/disintegration tests hardness/friability tests and tests for particle size and polymorphic form. Some of these tests may be precluded, or additional tests may be added as dictated by the chemistry of the pharmaceutical or the dosage form. 

Apart from food industry (see Chapter 8), NIR chemical imaging has so far primarily been applied to qualitative and quantitative product characterization in the pharmaceutical industry. The ability to visualize and assess the compositional heterogeneity and structure of the end products is extremely important for both the development and manufacture of solid dosage forms [20]. Hence, NIR chemical images have been used to determine authenticity, content uniformity, particle sizes and distribution of sample components, polymorph distributions, moisture content and location, contaminations, coating and layer thickness, as well as a host of other structural details [21-29]. 

The main attraction of hyperspectral imaging is to obtain the complete picture of the sample. It has been reported that particle size or blending quality (spatial distribution characteristics) is as important to the performance of a pharmaceutical product as its chemical composition [5, 6]. Hence, by characterizing both the chemical and spatial composition of the sample, hyperspectral imaging can provide valuable insight that bridges the relationships between processing and perfor-... 

The optical microscope is a valuable tool in the laboratory and has numerous applications in most industries. Depending on the type of data that is required to solve a particular problem, optical microscopy can provide information on particle size, particle morphology, color, appearance, birefringence, etc. There are many accessories and techniques for optical microscopy that may be employed for the characterization of the physical properties of materials and the identification of unknowns, etc. Utilization of a hot-stage accessory on the microscope for the characterization of materials, including pharmaceutical solids (drug substances, excipients, formulations, etc.), can be extremely valuable. As with any instrument, there are many experimental conditions and techniques for the hot-stage microscope that may be used to collect different types of data. Often, various microscope objectives, optical filters, ramp rates, immersion media, sample preparation techniques, microchemical tests, fusion methods, etc., can be utilized. 

The characterization of the physical properties of pharmaceutical compounds under development is often conducted using a variety of techniques including DSC, TGA, XRD, HSM, solid-state nuclear magnetic resonance (NMR), infrared (IR) and Raman spectroscopy, moisture uptake, particle size analysis, scanning electron microscopy (SEM), and micromeritic assays. A typical initial analysis of a pharmaceutical compound under development in a materials characterization group would include DSC, TGA, HSM, and XRD analyses. These four techniques are chosen because the data generated from them, when viewed collectively, comprise a relatively complete initial analysis of the physical properties of the compound. The DSC, TGA, and HSM assays... 

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