Sulfanilamide formulation

An un-safely formulated sulfanilamide preparation kills 107 people, mainly children. 

It should never be lost sight of that one of the major reasons for the 1938 FD C Act was a public health disaster caused by a drug formulation mistake. In the 1930s, the Massengill Company s use of diethylene glycol in elixir of sulfanilamide led to 105 deaths. This same disaster was, by the way, repeated in Haiti in 1995 and 1996 (O Brien et al., 1998). Such considerations are also overlooked in clinical safety evaluations, though the history of their directly and indirectly causing problems, even to the current day, is extensive (Winek, 2000). 

In 1937, 107 people died when the drug sulfanilamide was wrongly formulated. 

The law of 1906 was only a beginning. It did not regulate the safety and effectiveness of drug formulations. This was no more evident than in the case of mass poisoning which resulted from the consumption of "elixir of sulfanilamide" produced by the S.E. Massengill Company of Bristol, Tennessee. Between September and October 1937 doctors had prescribed almost 12 gallons of a 10% solution of sulfanilamide in an ethylene glycol(antifreeze) solvent flavored with saccharin, caramel, amaranth, and raspberry extract. The company s chief chemist, Harold Watkins, was not aware of the toxicity of that concentration of the solvent. 

In 1935, D. D. Woods found that the growth inhibition of sulfanilamide was reversed by yeast extract.d From this source, in 1940 he isolated p-aminobenzoic acid and demonstrated that the inhibitory effect of 3 x 10 1 M sulfanilamide was overcome by 6 x 10 8 M p-aminobenzoate. The relationship between the two compounds was shown to be strictly competitive. If the sulfanilamide concentration was doubled, twice as much p-aminobenzoate was required to reverse the inhibition as before. These facts led to the formulation by Woods and by P. Fildes (in 1940) of the... 

For the logarithmic value of kAc, Equation 13 and its modification, Equation 14, were formulated, where KA° is the dissociation constant of sulfanilamide, a, p c p, and c are constants, and [H+] is the hydrogen ion concentration in the blood. We used Equation 14 to analyze the acetylation data. The second term on the left of Equation 14 expresses the dissociation effect of the free drug, but it does not mean that the neutral form is only responsible for metabolism. 

A time span of 33 years has elapsed since the original formulation of the antimetabolite theory by Fildes1 based upon the discovery by Woods2 of the biological antagonism between sulfanilamide (1 b) and p-aminobenzoic acid (la), two compounds strikingly similar to each other in chemical structure and molecular dimensions (see illustration). Up to the present day, this theory... 

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). 

Sulfanilamides Pharmaceutical formulation and blood As 4,6-dinitrobenzofuroxane derivatives... 

The estimation of catechol and its derivatives such as dopamine hydrochloride, levodopa, methyldopa, and adrenaline hydrochloride in both pure form and in pharmaceutical formulation is based on the interaction of diazotized sulfanilamide with catechol derivatives in the presence of molybdate ions in acidic medium. Absorbance of the resulting red-colored product is measured at 490 nm for pyrocatechol and at 500 nm for other catechol derivatives. The color reaction is stable for 24-30 h. 

In the strip formulation of the Nitm-Test sulfanilamide reacts with nitrite in an acidic buffer medium to form a diazonium salt, which couples with 3-hydroxy-l,2,3,4-tetrahydrobenzoquinoline to give a red azo dye. 

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