Chemical stability hydrolysis effects

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 ... 

Thus the effects of CyDs on the hydrolysis of HCFU were studied in the hope of improving the chemical stability of HCFU in aqueous solution. Figure 4 shows log rate constant(K)-profiles for the hydrolysis in the absence and presence of 3"CyD over the pH range of 5.0-12,5 at 37°C. 

The results presented in Table III show that any substitution in the 6a-position of penicillin G or penicillin V reduces both enzyme inhibition and antibacterial activity. In contrast, introduction of a 7a-methoxy group into cephalosporins results in antibiotics that are better inhibitors of transpeptidase than their unsubstituted counterparts, although they do not necessarily possess better antibacterial properties (Table III). To test the effect of 6a-substitution in penicillins and 7a-substitution in cephalosporins on the chemical stability of these respective 3-lactams, the relative rates of hydrolysis of the substituted compounds were determined in aqueous solution at pH 10 (Table IV). The results show that 7a-methoxy substitution in cephalosporins has no pronounced effect on the reactivity of the p-lactam, which is in contrast to the three- to fivefold decrease in reactivity found with 6a-methoxy substitution in penicillins G and V. Indelicato and Wilham (1974) have suggested that loss of... 

Chemical Stability.—Oae et have reported three additional methods for the cleavage of sulphonium ylides. Reduction with dithioacetic acid afforded anisole and tosylamide in the case of the sulphidimine (23), but with the ylide (24) the overall effect simply was hydrolysis. With acetic... 

The task for medicinal chemists was to produce analogues of physostigmine with similar activity and fewer side effects (especially on CNS) and with better chemical stability. Miotine (Fig. 16.9) followed physostigmine as a first synthetic AChE inhibitor. It is still prone to chemical hydrolysis and its non-permanently charged tertiary... 

Now we turn to a discussion of the influence of a-substitution at C(6) or C(7) on the chemical reactivity of the lactam ring (Table 5.4,B). This substitution has been introduced mainly to improve lactamase stability (see Sect. 5.2.2.2). The insertion of an additional a-substituent at C(6) or C(7) of penicillins or cephalosporins, respectively, has a relatively small effect on the rate of base hydrolysis [82] [83], 6a-Methoxypenicillin is hydrolyzed at a rate that is approximately half that observed for the unsubstituted parent penicillin. This decrease is due mainly to unfavorable steric interaction between the... 

Furthermore, by in vitro experiments, it has been verified that stereospecific activation of alprenoxime is organ-specific, occurring in the eye and not systemically. When administered locally to rabbits, marked decreases in intra-ocular pressure were observed, whereas oral administration elicited almost no cardiac effects. Such ketoximes represent promising chemical delivery systems in the treatment of glaucoma However, a major limitation is their poor stability in solution, seemingly due to hydrolysis of the oxime function. 

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