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[e-drug] Stability and administration of drugs at very low temperature (4)

E-DRUG: Stability and administration of drugs at very low temperature (4)

Dear All

Following from Susan's comment, there is another class of drugs that must not 
be frozen while in injectable form. These are the aminobenzylpenicillins (e.g., 
amoxicillin) and related cephalosporins, plus a few others like cycloserine. 
These drugs  degrade by second order nucleophilic reactions, which 
characteristically degrade faster in higher concentrations than in lower 
concentrations. Should freezing occur, solutions of these drugs initially 
produce ice crystals. This has the effect of increasing the concentration of 
the drug, increasing the chance that molecules will collide in solution and 
react with each other. It was shown as much as 40 years ago that such drugs can 
be as unstable at -20 C as at +26 C (in the case of ampicillin).

These injection solutions MUST be stored at the recommended temperature 
(usually 2-8 C)


Richard Prankerd
Senior Lecturer
Faculty of Pharmacy and Pharmaceutical Sciences
Drug Delivery Disposition and Dynamics 
Monash Institute of Pharmaceutical Sciences� 
Monash University (Parkville Campus)
381 Royal Parade, Parkville
Victoria 3052, Australia
Tel: Int + 61 3 9903 9003
Fax: Int + 61 3 9903 9583
E-mail: richard.prankerd@monash.edu 

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