Nitrazepam decomposition

Rguie4.19 Logarillim of llie nitrazepam decomposition constant, k, as a function of relative humidity at various temperatures. 

W. Loewe, M. Soliva, and P. P. Speiser, Decomposition of nitrazepam in tablets in the presence of silica and calcium phosphate, Drug Made Germany, 25 158 (1983). 

Finally, as examples of lactam ring hydrolysis we can consider the decomposition of nitrazepam and chlordiazepoxide, which is discussed in more detail later (section 4.2.7). Other dmgs, apart from the benzodiazepines, which are susceptible to hydrolysis include the penicillins and cephalosporins. 

The decomposition of many dmgs involves two or more pathways, the preferred route of reaction being dependent on reaction condition. Nitrazepam (VI) decomposes in two pseudo first-order parallel reactions giving different breakdown products in solution and in the solid state, as illustrated in Scheme 4.13. Decomposition of nitrazepam tablets in the presence of moisture will occur by both routes, the ratio of the two products being dependent on the amount of water present. 

Scheme 4.13 Simplified decomposition scheme for nitrazepam (VI) in the solid state and aqueous solution. The main decomposition product is 2-amino-5-nitrobenzophenone (VII) in aqueous solution and 3

The stability of solid dosage forms is usually very susceptible to the moisture content of the atmosphere in the container in which they are stored (see section 4.4.3) A linear relationship between log k and the water vapour pressure for vitamin A palmitate beadlets in sugar-coated tablets has been found. Similarly, a linear relationship between the logarithm of the rate constant for the decomposition of nitrazepam in the solid state and the relative humidity has been established (Fig. 4.f9). The need for consideration of the effect of moisture on stability has been stressed by Carstensen, who stated that stability programmes should always include samples that have been artificially stressed by addition of moisture. One purpose of a stability programme should be to define the stability of the dosage form as a function of moisture content. 

The decomposition products of 5-phenyltetrahydro-l,2-oxazinane-2,4-dione (a metabolite of felbemate), felbemate acid carbamate, l-hydroxy-2-phenylpropamide, and 2-phenylaciylamide were separated on a C g column (2 = 214 nm) in 11 min using a 20/80 acetonitrile/water (1% acetic acid) mobile phase. Peak shapes were good and baseline resolution was obtained [1407], Fifteen benzodiazepines (e.g., 7-aminoclonazepam, clonazepam, flunitrazepam, 7-aminonitrazepam, nitrazepam. 

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