Small Molecules: Process Intensification and Continuous Synthesis
Anthony J. Hickey, Sandro R.P. da Rocha in Pharmaceutical Inhalation Aerosol Technology, 2019
Chemical reactions to produce pharmaceuticals have significant diversity in terms of reaction type and mechanism. In addition, many of the processes are scaled up very quickly to pilot plant reactors before full chemistry characterization can take place. Understanding of reaction kinetic data is an important mechanism for interpreting reaction scalability and interaction with mass transfer processes, and therefore chemists should strive for early collection of kinetic data whenever possible. Fortunately, modern equipment such as controlled reactors and in-situ FTIR are reducing the barrier to gathering such information. An excellent introduction to in-situ monitoring as an enabling technique for gathering of reaction progress data has been outlined by Donna Blackmond.23 Blackmond has outlined that reaction progress kinetics can be conducted very simply if one has a method of in-situ analysis, as well as a curve-fitting software program. In-situ FTIR spectroscopy can be used to monitor the reaction concentration (or conversion) profile and converted to rate information via the integral method. The confidence of this data can be increased by using an orthogonal off-line analytical method such as HPCL or GC, which are routinely available during product development. In a follow-up paper, Blackmond outlined the use of both reaction calorimetry, as well as in-situ FTIR measurements to determine the mechanism of catalytic reactions, outlining how these two techniques can be used in a complementary fashion.24
Chemistry and Isotopes of Iodine
Erwin Regoeczi in Iodine-Labeled Plasma Proteins, 2019
Elements are those substances that are not resolved into simpler entities by chemical processes. The smallest amount of an element that participates in a chemical reaction is an atom. The components of an atom are the electron (charge — 1; mass 5.5 × 10-4), the proton (charge +1; mass 1), and the neutron (charge 0, mass 1). Protons and neutrons constitute the atomic nucleus. The number of protons in the nucleus gives the atomic number of the element and determines the identity of the atom as an element. The atomic number is given by a subscript preceding the abbreviation of the element, e.g., 53I. The properties of the elements are in periodic dependence on their atomic numbers. In the periodic table, the vertical arrangement of the elements is called a group (a total of 11) and the horizontal arrangement periods (7 altogether).
Theory of Granulation
Dilip M. Parikh in Handbook of Pharmaceutical Granulation Technology, 2021
When considering a scale of scrutiny of the order of granules, we ask what controls the rate processes, as presented in detail in the previous sections. This key step links formulation or material variables to the process operating variables, and successful granulator design hinges on this understanding. Two key local variables of the volume element, A, include the local-bed moisture and the local level of shear (both shear rate and shear forces). These variables play an analogous role of species concentration and temperature in controlling kinetics in a chemical reaction, with the caveat that granulation mechanisms are primarily path functions in the thermodynamic sense, with work input as opposed to time controlling deformation mechanisms. In the case of chemical reaction, increased temperature or concentration of a feed species generally increases the reaction rate. For the case of granulation considered here, increases in shear rate and moisture result in increased granule/powder collisions in the presence of binding fluid, resulting in an increased frequency of successful growth events and increases in granule growth rate. Increases in shear forces also increase the granule consolidation rate and aid growth for deformable formulations. In the limit of very high shear (e.g., due to choppers), they promote wet and dry granule breakage or limit granule growth. In the case of simultaneous granulation and drying, bed and gas-phase moisture, temperature control, heat and mass transfer, and the impact of drying kinetics on currrent bed moisture should be considered.
A comparative study on the raft chemical properties of various alginate antacid raft-forming products
Published in Drug Development and Industrial Pharmacy, 2018
Peter W. Dettmar, Diana Gil-Gonzalez, Jeanine Fisher, Lucy Flint, Daniel Rainforth, Antonio Moreno-Herrera, Mark Potts
Alginate-based products are complex formulations as they require three chemical reactions to take place simultaneously, alginate transforming to alginic acid, sodium carbonate reacting to form carbon dioxide, and calcium carbonate releasing free calcium ions to bind with alginic acid and provide strength to the raft. Small differences in the way products are formulated can have a significant effect on the kinetics of these reactions taking place asynchronously and leading to significant differences in product performance. The chemical reactions then control and influence three key processes: (i) the efficient utilization of the alginate within a formulation, (ii) the subsequent alginate content within the raft, and (iii) the neutralization profile of the raft itself. The discussed chemical reactions are illustrated in Figure 6.
S-Carboxymethyl-l -cysteine: a multiple dosing study using pharmacokinetic modelling
Published in Xenobiotica, 2021
Glyn B. Steventon, Stephen C. Mitchell
Studies using cell-free systems assessed the scavenging activity of SCMC on reactive oxygen species generated from hypochlorous acid (HOCl), hydrogen peroxide (H2O2), peroxynitrite (ONOO–) and hydroxyl radicals (HO•; produced from H2O2/FeCl3) during incubation in phosphate buffer (Nogawa et al. 2009). Similar studies were reported for the SCMC-lysine salt (Brandolini et al. 2003). The drug was effective between concentrations of 0.179 μg/ml (against 54 μM NaOCl) and 179.2 μg/ml (against 1 μM ONOONa; 3 mM H2O2/FeCl3). However, these systems are purely chemical reactions and dependent upon the relative concentrations of reactants employed. Owing to its chemical structure, containing a sulphur moiety, the drug is able to scavenge reactive oxygen species. To have a direct biological meaning such experiments must be undertaken at concentrations of reactive oxygen species that actually occur within the living cell and even then, there are many confounding factors.
Risk assessment of heterogeneous TiO2-based engineered nanoparticles (NPs): a QSTR approach using simple periodic table based descriptors
Published in Nanotoxicology, 2019
Joyita Roy, Probir Kumar Ojha, Kunal Roy
This indicates that the atoms containing lower number of valence shell electrons will have higher descriptor values, as it is inversely proportional to the number of electrons in the principle valence shell taking part in the chemical reaction. The descriptor also determines the kinetics of corrosion rate and estimates the oxidizing power of metal in specific environment. The oxidizing power can be determined through the oxidation potential of a metal, which gives the measure of the likelihood of a metal to move from lower oxidation state to higher oxidation state. The transition metals can exist in different oxidation state as they have partially filled -d and -f orbital shells. The elements with low number of valence electrons will have less oxidation state and metals with less oxidation state are more harmful than the elements with higher oxidation or stable oxidation state (Walker et al. 2003). The positive regression coefficient of this descriptor suggests that the toxicity towards hamster ovary cell will increase with an increase in the numerical value of this descriptor as shown in case of nanoparticles 6.5Ag_0.5Pt and 6.5Ag_0.25Pt (the Electrochemical Equivalent values are 27.06975 and 26.614825 (g/amp-hr) and their corresponding toxicity values are 5.8 and 5.84 respectively) and vice versa as shown in nanoparticles 0.05Au_0.05Pt and 0.1Au (the Electrochemical Equivalent values are 0.213465, 0.24496 (g/amp-hr) and their respective toxicity values are 4.67 and 4.56).
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