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Drug Substance and Excipient Characterization
Published in Dilip M. Parikh, Handbook of Pharmaceutical Granulation Technology, 2021
Parind M. Desai, Lai Wah Chan, Paul Wan Sia Heng
Density is an important parameter due to its influence on particle mechanical properties [36], powder porosity [37], and powder fluidization [38]. The bulk density of a mixed excipient powder used for tablet preparation has been found to affect the disintegration time of the tablet in a mouth [39]. Similarly, it can affect the disintegration of granules. On the other hand, the true density can serve to assure the formulator of the identity of the material. Determination of particle density is not straightforward as it can be carried out by many different techniques, with differing interpretations.
Engineering Stable Spray-Dried Biologic Powder for Inhalation
Published in Anthony J. Hickey, Sandro R.P. da Rocha, Pharmaceutical Inhalation Aerosol Technology, 2019
Nicholas Carrigy, Reinhard Vehring
Trehalose and leucine have been studied extensively as excipients for particles containing biologics. In trehalose and leucine systems, it is desirable to dissolve the trehalose in the liquid feed with a low initial saturation ratio so that it will precipitate near the end of the drying process into an amorphous solid suitable for stabilization of biologics. By contrast, leucine should be dissolved in the liquid feed with a high initial saturation ratio, leading to a long time available for crystallization, which allows crystals to grow at the surface of the drying droplet and form a shell that decreases particle cohesiveness. The shell is typically not exclusively composed of leucine, but can nevertheless lead to acceptable dispersibility [126]. As the leucine shell forms early in the evaporation process, while the droplets are relatively large, hollow particles, with low particle density, ρp, result; it has been shown that more void space and lower particle density result with increasing time available for crystallization [208,212]. The particle density can be predicted from measurements of volume equivalent diameter, dv, (e.g. by estimating the hydrodynamic diameter using scanning electron microscopy for a sufficiently large number of particles) and aerodynamic diameter, da, (e.g. using aerodynamic particle sizing techniques such as impactors), using the relationship obtained by equating the settling velocities [24,219]:
Physicochemical properties of respiratory particles and formulations
Published in Anthony J. Hickey, Heidi M. Mansour, Inhalation Aerosols, 2019
where 𝜌1 is the unit density (e.g., 1 g/cm3) and 𝜌 is the particle density. Cd is the particle drag coefficient which is a function of the particle Reynolds number, Re = ud/υ, where υ is the air kinematic viscosity, u is the particle (slip) velocity relative to the air stream. ReA and Re denote numbers for particles with diameters dA and d, respectively. Cc is the Cunningham slip correction factor dependent on the particle diameter (18,19). Experimentally, the aerodynamic particle size distribution (APSD) is typically measured using cascade impactor devices such as Andersen cascade impactor, next generation cascade impactor (NGI) and muti-stage liquid impinger (MSLI), all of which operate on the principle of particle classification by using a series of jets and collection plates with different Stokes numbers (see below). APSD can also be measured using time-of-flight (TOF) techniques (18).
Investigation of mixing homogeneity of binary particle systems in high-shear wet granulator by DEM
Published in Drug Development and Industrial Pharmacy, 2023
Renyu Fan, Mengtao Zhao, Linxiu Luo, Yuting Wang, Kangming Zhou, Zeng Liu, Yu Zhou, Tianbing Guan, Huimin Sun, Chuanyun Dai
In addition to the cohesive forces that exist between particles, other particle parameters, most notably the difference in particle density and size, have a substantial impact on particle mixing [9–11], an increase or decrease in either of these properties will have an effect on the tendency to separate or mix particles. The Brazil nut effect (BNE), which frequently occurs in particle systems of different sizes, and interparticle osmosis are the key mechanisms for particle separation or mix in binary particle systems of varying densities and sizes. When different types (sizes) of particles are present, according to this principle, the larger size particles rise to the top of the container when it is shaken or combined [12]. If the density of the particles changes, a Reverse-Brazil nut effect (RBNE) may occur, causing large particles with higher densities to sink to the bottom. This phenomenon has been observed in numerous studies [13–15].
Production of rice bran oil (Oryza sativa L.) microparticles by spray drying taking advantage of the technological properties of cereal co-products
Published in Journal of Microencapsulation, 2022
Nathan H. Noguera, Dyana C. Lima, José Claudio Klier Monteiro Filho, Rodney A. F. Rodrigues
In our work, real particle density ranged between 1.188 and 1.275 g.cm−3, similar to that reported by Drusch et al. (2009). It should be considered that not only the chemical composition but also the spray drying conditions, such as air inlet temperature and the dispersion properties (viscosity, aeration, and water content) can affect the structure of the powders and the density parameters. Furthermore, the amount of air trapped inside each particle depends on the volume of air present in the dispersion. The growth of air bubbles is a consequence of homogenisation and atomisation processes and is usually influenced by the airflow during the drying process. Thus, a greater volume of air filling the particles can result in aerated particles, which consequently modifies the real density (Soottitantawat et al. 2003).
Estimates of carbon nanotube deposition in the lung: improving quality and robustness
Published in Inhalation Toxicology, 2020
Matthew D. Wright, Alison J. Buckley, Rachel Smith
Whilst particle density is now generally being assessed in in vivo studies, albeit with potential instrumentation and fundamental issues affecting accuracy of these assessments, we also advocate in future studies reporting as much additional information on particle morphology as possible, to improve density estimates but also in anticipation of further model developments and/or to aid model validation, in particular with respect to interception. For example, from TEM image processing, a range of geometric parameters including Feret, Martin or ‘envelope’ diameters (Ku and Kulkarni 2015; Trubetskaya et al. 2017) and projected area can be obtained, details of which, in conjunction with computational modeling and experimental deposition measurements, may provide further insight into CNT particle behavior in the lung.