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2775494 
Technical Report 
Effect of solvents on the potency of chlordiazepoxide, diazepam, medazepam and nitrazepam 
Crankshaw, DP; Raper, C 
1971 
IPA/72/59076 
Pharm 
REF 14 
313-321 
English 
IPA COPYRIGHT: ASHP The interactions of various solvents with the benzodiazepines, chlordiazepoxide HCl, diazepam, medazepam and nitrazepam have been examined using loss of the righting reflex in mice as a measure of pharmacological activity. Chlordiazepoxide HCl (Librium), diazepam (Valium), medazepam (Nobrium) and nitrazepam (Mogadon) were formulated in one of the following vehicles for I.P. injection: (1) dimethyl sulfoxide; (2) propylene glycol (45% v/v), ethanol (10% v/v), benzyl alcohol (1.5% v/v), sodium benzoate (9.8% w/v), benzoic acid (0.24% w/v) in water; (3) glycofurol (45% v/v), ethanol (10% v/v), benzyl alcohol (1.5% v/v) in water; and (4) a suspending vehicle of sodium carboxymethylcellulose (0.5% w/v), polysorbate 80 (0.5% v/v), phenylmercuric nitrate (0.001% v/v) in water. The data indicated that the absolute and relative potencies of these drugs may be modified by solvents used in parenteral preparations. These interactions may cause either a reduction or increase in the actual potency of the drugs involved. A table noting the most suitable solvent for each of the drugs studied is included.