Chemical stability reaction order

Lawrence (1996) summarized the answers of the experts and calculated the total scores for each parameter. According to this summary the most important parameters for inherent safety were inventory and toxicity. Other important factors were, in this order, chemical stability, temperature, pressure, flammability and explosiveness, which were considered to be essential by all experts. Also flash points and side reactions were quite important. 

The reaction is acid-catalyzed and yields isocyclosporin A (iso-CsA, 6.58, Fig. 6.23) as the major product. At 50°, the kinetics of the first-order reaction were k=l x 10 6 s 1 (tV2 ca. 1.1 d) at pH 1, and k= 1. 7 x 10 8 s 1 (tv2 ca. 1.2 y) at pH 4. Iso-CsA (i.e., the O-peptide) had a much greater chemical stability than CsA (i.e., the A-peptide) under acidic conditions, in contrast to other findings where the opposite was true. Interestingly, O-acclyl-CsA did not yield iso-CsA and exhibited a much greater stability than CsA, consistent with the nucleophilic mechanism mentioned above. 

In considering chemical stability of a pharmaceutical, one musf evaluate the reaction order and reaction rate. The reaction order may be the overall order (the sum of the exponents of the concentration terms of fhe rate expression), or fhe order with respect to each reactant (the exponent of the individual concentration term in the rate expression). The reaction rate expression is a description of the drug concentration with respect to time. Most commonly, zero- and first-order reactions are encountered in pharmacy. 

Reactions with monofunctional reagents are for example carried out in order to increase the thermal and/or chemical stability of the end groups (Poly-oxymethylenes, Example 5-7). Reactions with bifunctional reagents can be used to enlarge the degree of polymerization or to synthesize block copolymers (see Sect. 4.2.1). 

As discussed in Chapter 1 (Sections III and TV), the kinetics of drug degradation has been the topic of numerous books and articles. The Arrhenius relationship is probably the most commonly used expression for evaluating the relationship between rates of reaction and temperature for a given order of reaction (For a more thorough treatment of the Arrhenius equation and prediction of chemical stability, see Ref. 13). If the decomposition of a drug obeys the Arrhenius relationship [i.e., k = A exp(—Ea/RT), where k is the degree of rate constant, A is the pre-exponential factor ... 

To describe the chemical reactivity in the context of DFT, there are several global and local quantities useful to understand the charge transfer in a chemical reaction, the attack sites in a molecule, the chemical stability of a system, etc. In particular, there are processes where the spin number changes with a fixed number of electrons such processes demand the SP-DFT version [27,32]. In this approach, some natural variables are the number of electrons, N, and the spin number, Ns. The total energy changes, estimated by a Taylor series to the first order, are... 

In most of the reactions discussed above the resulting monolayers are terminated by a methyl group. While these types of monolayers are useful for passivation and chemical stabilization, the low reactivity of the terminal group makes further manipulation of the surface physical or chemical properties difficult. In order to incorporate more complex organic or bio-organic structures at the interface, new strategies for coupling these molecules to the surface are required. 

The ratio of the currents for the backward and forward processes, = IJI, is then a measure of the chemical stability of the intermediate. For the no reaction case,= 1 — 2 (= 0.2929). In handling data for kinetic measurements a normalized current ratio is calculated by dividing the experimental values by 0.2929, i.e. that for the no reaction case. With reference once again to reactions (1) and (2), the rate constant for (2) can be calculated from k = 0.411/x where x is Tf when the normalized current ratio is 0.5 (Childs et al., 1971). The practical limit for the use of DPSC in non-aqueous solvents is pulse widths of the order of 1 ms. 

In these studies, thermodynamic equilibrium conditions were assumed. Constant pH monitoring was used as an estimator of the equilibration times involved, since a stable pH is an overall indicator of the Internal chemical stability of pH dependent processes. In order to allow the assumptions of atmospheric O2 and CO2 partial pressures, water scrubbed compressed air was pumped into the reaction vessels under constant temperature and constant vigorous mixing conditions. The air was introduced by fritted glass bubblers which had been teflon coated while air flowed through them in order to minimize the glass-solution interface. 

The effect of the autoclave cycle, i.e., fill, heat-up, peak dwell and cool down, on the theoretical chemical stability of compounds intended for IV injection has been investigated by Parasrampuria et al. (1993). Assuming first-order degradation kinetics, i.e., hydrolysis, the amount of degradation was calculated for any point during the above process. Although the results were calculated for first-order kinetics, the authors estimated that the calculations were applicable to other reaction orders, i.e., zero and second. Acceptable reasons for not proceeding with a terminally sterilized product are as follows ... 

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