Date of Award

1968

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Pharmaceutical Sciences

First Advisor

Anthony N. Paruta

Abstract

The degradation of hydrocortisone sodium succinate was followed in aqueous systems buffered at pH values of 6. 9, 7. 2 and 7. 6 at 70°c. The decomposition pathway can be described by an irreversible consecutive first order process which followed a two-step sequence: ester-k1-alcohol k2 degradation products. Hydrolysis of the steroid ester yields the alcohol which. in turn degrades to a fraction devoid of the 17 -dihydroxyacetone function. For the pH range studied, ester hydrolysis was assumed to occur by way of an intramolecular attack of the anion on the ester carbonyl carbon. A reaction pathway for the decomposition of the steroidal alcohol is proposed, where an etio acid and formic acid are produced by way of an oxidative mechanism. No attempt was made, however, to qualitatively determine the exact form the corticosteroid assumed subsequent to the degradation of the dihydroxyacetone function. Determination of the relevant species at various time intervals involved a spectrophotometric analysis using the blue tetrazolium assay which is specific for the intact 17 -dihydroxyacetone chain. The initial and subsequent samples were calculated on the basis of the absorbance reading of the initial sample as 100%. The first rate constants, kl, at the various pH levels were evaluated by a semilog plot of steroid ester concentration versus time and found to increase with increasing hydroxyl-ion concentration. Three documented methods which employed differential equations or dimensionless parameters were used to evaluate the second rate constant, k 2 • Two additional methods were derived in an attempt to simplify the calculations and were used successfully to calculate the second rate constant for the decomposition of hydrocortisone sodium succinate.

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