Search

Solutions containing hydrogen sulfite, HSO3−, and sulfite, SO32−, species appear to undergo oxidation at the expense of the divalent anion; this is a consequence of the different strengths of the two acids, HS03−and HS04−. A theoretical equation has been derived which permits calculation of the rate of loss of total sulfurous acid species [ —d(St)/dt] from a pH-time plot of the oxidizing system. Rapid and reproducible rate studies of oxidizing sulfurous acid salt systems have been made possible through the development of an automated apparatus. Applications of the sensitive radical mediated oxidizing sulfite system for detecting presence of a wide variety of compounds in p.p.m. range are discussed. Empirical equations can be used to obtain semiquantitative analyses of compounds which inhibit the rate of sulfite oxidation in low (10−6M) concentrations.

Sulfurous acid salts in common with many pharmaceutical antioxidants and oxygen-sensitive drugs undergo oxidation by a radical process. This has important implications in the testing and evaluation of oxidative tendencies of formulations since radical processes are inordinately sensitive to slight amounts (10−6M) of compounds acting as radical inhibitors or initiators. Measurable inhibition of the rate of sulfite oxidation occurred in the presence of 10−6M DMA or DMF; the inhibition is described by an empirical equation. Effect of hydrogen ion concentration on the oxidation of sulfurous acid salts was studied in detail and the results described in terms of a theoretically derived equation. Experimental data are presented in corroboration of the Abel theoretical equations and radical mechanism for sulfite oxidation.

Many aqueous, oxygen-labile pharmaceutical systems may be effectively protected by the antioxidant activity of sulfurous acid salts. The sulfite system is inordinately sensitive to trace amounts of heavy metal catalysts and a wide variety of organic compounds which act as oxidation inhibitors. Mechanism of sulfite oxidation in the presence of known inhibitors at levels normally encountered in pharmaceutical formulations appears to involve heavy metal catalysts. At the concentration (p.p.m.) of heavy metals normally present in formulations, the rate of oxidation and antioxidant activity is directly dependent upon the heavy metal concentration. However, a slow but measurable rate of sulfite oxidation occurs in systems especially purified to remove metal ions. The copper-catalyzed oxidation of sulfurous acid salts in buffered systems containing ethanol as an inhibitor may be described by first-order kinetics. The pH profile of the absolute initial rate of the copper-catalyzed oxidation has been experimentally determined and found to be in reasonable agreement with a theoretically derived curve.

Automation of dissolution studies of solid dosage forms has been achieved through the use of a timer-controlled sampling and dilution system which automatically removes filtered samples from the dissolution apparatus, makes reproducible dilutions, and records the absorption of the diluted sample as a function of time. The U.S.P. tablet disintegration apparatus was employed to provide constant, reproducible agitation. Versatility and reliability of the apparatus has been demonstrated by comparing automated dissolution rate results with values obtained by independent, manual analyses. Design requirements and specifications of individual components have been discussed in detail so that other functionally equivalent units may be employed to achieve comparable results with those reported in this study.

Bisulfite reduction of p-nitrobenzyl alcohol appears to follow a Piria mechanism leading to formation of α-hydroxy-6-sulfoamino-m-toluenesulfonic acid. Stoichiometry of the reaction involves one mole of nitro compound and three moles of bisulfite; pH profile of the initial rate of the stoichiometric reaction has been studied. Preliminary kinetic studies indicate an apparent heat of reaction of about 22Kcal. mole−1. This complicated sequential reduction reaction appears to involve two mechanistic pathways: a rate-determining initial SN1 reaction dominates at pH 4, while at pH 7 the initial rate-determining reaction appears to possess typical SN1 characteristics.