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Granulation Process Modeling
Published in Dilip M. Parikh, Handbook of Pharmaceutical Granulation Technology, 2021
Nucleation refers to the formation of initial aggregates that are typically a result of interaction between the binder spray droplets and the powder in the device. This mechanism provides the initial stage for further growth through a number of mechanisms. A number of nucleation models have been proposed in the literature [9–12].
Nephrolithiasis: etiology, stone composition, medical management, and prevention
Published in J Kellogg Parsons, E James Wright, The Brady Urology Manual, 2019
Nucleation: Nucleation is the process by which stones form around a core, or nucleusHomogeneous stone nuclei form in solutionHeterogeneous stone nuclei form around existing structures, such as cellular debris.
Overview of the delivery technologies for inhalation aerosols
Published in Anthony J. Hickey, Heidi M. Mansour, Inhalation Aerosols, 2019
Daniel F. Moraga-Espinoza, Ashlee D. Brunaugh, Silvia Ferrati, Lara A. Heersema, Matthew J. Herpin, Patricia P. Martins, Hairui Zhang, Hugh D.C. Smyth
The second step is condensation. In a supersaturated vapor system, as the temperature decreases, the partial vapor pressure increases above the saturated vapor pressure and condensation occurs (46,48). This temperature decrease may occur as the vapor moves away from the source of heat. Condensation can either occur by heterogeneous nucleation or homogeneous nucleation. Heterogeneous nucleation depends on the presence of condensation nuclei (such as small particles), while homogeneous nucleation (also known as self-nucleation) corresponds to the process of particle growth without the presence of condensation nuclei. Heterogeneous condensation generates more controlled monodisperse aerosols compared to homogeneous nucleation. Homogeneous nucleation requires higher supersaturation ratios than heterogeneous nucleation (46–48). Various factors influence the aerosol quality. For example, Leong (47) found an additional step can be included to improve monodispersity of the aerosol, by reheating and recondensing the droplets. Monodispersity could also be further improved by changing the geometry of the aerosol generator (e.g., the volume–to–surface area ratio of the container) (47,49).
Thermodynamic and kinetic approaches for drug discovery to target protein misfolding and aggregation
Published in Expert Opinion on Drug Discovery, 2023
In this kinetic network, the aggregating proteins are simultaneously the reactants (the monomers), the products (the amyloid fibrils), the intermediates (the oligomers) and the catalysts (the amyloid fibril surfaces). It is thus important to identify the specific microscopic steps that contribute most to the generation of cytotoxic species [96,97]. In some cases, for example, in amyloid light chain amyloidosis, the cytotoxic species are the amyloid fibrils [2,13], while in other cases, for example, for Aβ in Alzheimer’s disease, the most dangerous species are the oligomeric intermediates [1–3,6,23,24]. The non-linear and interconnected nature of the kinetic network underlying Aβ aggregation makes it difficult to predict the effects of compounds that change the rate constants of specific microscopic steps on the production of oligomers [97] (Figure 3B, C). For example, reducing specifically primary nucleation delays the production of oligomers, but it may not change the total amount of oligomers produced at the end of the reaction. Drugs that inhibit primary nucleation would thus be preventative [34].
The effect of anionic Eudragit polymers on drug supersaturation and in vitro permeation improvement
Published in Drug Development and Industrial Pharmacy, 2023
Maryam Maghsoodi, Saeideh Mollaie Astemal, Ali Nokhodchi, Hossein Kiaie, Fatemeh Talebi
It has been proven that maintaining the supersaturated concentration of drugs in the presence of polymers is mainly due to the molecular interaction between drugs and polymers [33–35]. When an attractive interaction occurs between the drug and the polymer molecules, the nucleation and crystal growth rate of the drug can be slowed down. This in turn impedes precipitation and maintains the supersaturated concentration of the drug [36]. Many previous studies have shown that the inhibitory effect of polymers on drug crystallization is strongly correlated with polymer hydrophobicity and it is a key factor affecting the occurrence of interaction between the polymer and the drug molecules. On the contrary, in the case of a highly hydrophilic polymer, the polymer likely interacts more favorability with water molecules, resulting in a weak inhibitory effect of the polymer on drug crystallization [37–39]. Therefore, it is reasonable to assume that the degree of hydrophobicity of polymers determines the magnitude of the adsorption of polymers to the newly generated drug nuclei surface, which in turn impacts the efficiency of the polymers as a crystallization inhibitor. Consistently, our results regarding the inhibitory effect of Eu polymers on CNZ crystallization can be explained in terms of the hydrophobicity of the polymers.
The effect of some acrylic polymers on dissolution of celecoxib solid dispersion formulations
Published in Pharmaceutical Development and Technology, 2021
Maryam Maghsoodi, Ali Nokhodchi, Hadi Pourasghari Azar
It has been proven that maintaining the supersaturated concentration of drug by polymers is mainly because of the strength of drug-polymer molecular interaction, where imparting hydrophobicity to water-soluble polymers has been revealed to increase their capability to prevent crystallization (Warren et al. 2010; Ilevbare et al. 2013; Hsieh et al. 2014; Kiew et al. 2015; Xie and Taylor 2016; Mosquera-Giraldo et al. 2018; Frank and Matzger 2019). When an attractive interaction occurs between the drug and the polymer molecules, the nucleation and crystal growth rate of the drug can be slowed down. This, in turn, impedes precipitation and maintains the supersaturated concentration of the drug (Yokoi et al. 2005; Zimmermann et al. 2009). Therefore, in the present study, it is reasonable to assume that the difference in the ability of anionic Eu polymers to sustain CEX supersaturation might be attributed to the diverse potential of these polymers for unspecific hydrophobic interaction with CEX as a consequence of their different hydrophobicity.