Sulfacetamide, hydrolysis

Sulfacetamide was first prepared by Dohm and Diedrich (14) in 1938 and independently by Crossley et al. (15) in 1939. Sulfanilamide (I) is acetylated by acetic anhydride to give N N4- diacetyl derivative (II). The N4-acetyl group is removed by alkaline hydrolysis to yield sulfacetamide (III) which is crystallized by acidifying with hydrochloric acid. 

The hydrolysis of sulfacetamide solution has been studied colorimetrically after separation of the degradation products on silica gel with acetone-methanol-diethylamine (90 10 10) as solvent system (56). The method has a low precision with a coefficient of variation of about 7%. Sulfanilamide, in degraded sulfacetamide formulations, has been separated by TLC followed by spectrophotometric determination of the eluted component (91). 

The stability of sulfacetamide in 1 M HC1 at 40-70°C has been studied by HPLC methods. Three different stationary phases have been employed for the determination of sulfacetamide and its hydrolysis product, sulfanilamide, in degraded solutions (100). HPLC has been used to study the acid hydrolysis of sulfacetamide at elevated temperatures and for the identification of its degradation products (101). 

The hydrolysis of sulfanilamide solutions at sterilization temperatures has been studied. The rate of hydrolysis appears to be independent of pH in the range 7-9. About 1% loss results from heating at 120°C for 20 minutes or 115°C for 30 minutes, while steaming at 100°C for 30 minutes gives less than 0.5% degradation. The reaction is first-order with respect to sulfanilamide (56). Heating of sulfacetamide solutions at 100°C increases the rate of hydrolysis and the likelihood of sulfanilamide crystallization. The crystallization is minimised by buffering the solutions at pH 9.0 to 9.5. The concentration of sodium metabisulfite does not appear to have any effect on the extent of crystallization (106). 

Sulfacetamide sodium undergoes degradation in aqueous solution by two routes, oxidation and hydrolysis. Ophthalmic solutions of this compound frequently contain sodium metabisuifite as an antioxidant to decrease the rate of development of the yellow color characteristic of degraded solutions. Davies and coworkers have shown that sodium metabisuifite accelerates the hydrolytic degradation of sulfacetamide to sulfanilamide, whereas sodium edetate does not influence the rate. 

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