Anticancer agent temozolomide is stable in acidic conditions but degrades in the presence of water at pH>7. Storage of the prodrug as a powder or in tablet form leads to discoloration of the initially white substance to light pink or tan, which is indicative of degradation. This degradation lowers the effectiveness of the drug and has the potential to disconcert patients.
Ashwini Nangia and co-workers, University of Hyderabad, India, have developed a method to increase the chemical stability of temozolomide and prevent discoloration. Cocrystals of the anticancer agent with organic acids proved to be more stable than temozolomide alone. The half-lives of the cocrystals in blood plasma under physiological conditions were longer than that of pure temozolomide, and solid powders of the cocrystals were stable with no signs of discoloration for over six months, even at 75 % relative humidity.
The dissolution rates of the cocrystals with succinic acid and oxalic acid were comparable to that of pure temozolomide, thus making these the most promising for formulation development.
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- Crystal Engineering of Stable Temozolomide Cocrystals,
N. Jagadeesh Babu, Palash Sanphui, Ashwini Nangia,
Chem. Asian J. 2012.