Formulation in Pharmacy Practice   2nd Edition

CHLORAMBUCIL
 
 
Chlorambucil is freely soluble in alcohol and dilute alkali hydroxides.  Chlorambucil is practically insoluble in water but in the presence of water undergoes rapid hydrolysis.  The rate of hydrolysis is most rapid between pH 4.5 and 10.  Maximum stability is achieved at pH values less than 2, and the rate of hydrolysis can be slowed by adding ethanol or propylene glycol and by refrigeration.1

Dressman et al2 investigated the stability of a 2mg per mL suspension prepared from crushed tablets in a base of one third methylcellulose 9% solution (Cologel), and two thirds syrup, stored in amber glass bottles.  Decomposition at room temperature was rapid but 90% of original potency was maintained for 7 days at 5°C.   Sample numbers were small and this together with the inherent instability of such suspensions limits the practical application of the results.

Preparation of chlorambucil suspension should be avoided but if absolutely necessary it is advisable to prepare freshly every 24 - 48 hours.  Tablet dispersion prior to dose administration is probably the preferred option.  Another possibility would be to mix the chlorambucil tablets with a mixture of water, ethanol and propylene glycol as this may be more stable than an aqueous suspension.  Chlorambucil should be stored in airtight containers and protected from light.

REFERENCES
  1. Tobin M.B.  Chlorambucil.  In: Connors K.A., Amidon G.L., Stella V.J.  Chemical Stability of Pharmaceuticals, 2nd Ed. New York John Wiley: 322-27.
  2. Dressman J.B., Poust R.I.  Stability of allopurinol and of five antineoplastics in suspension.
    Am J Hosp Pharm 1983; 40: 616-18.
 
 
     

Formulation in Pharmacy Practice
2nd Edition
© 2001 PharmInfoTech
ISBN 0-473-07577-6