Stability of the nitrogen mustard mechlorethamine in novel formulations for dermatological use

Long term stability measurements were made for the nitrogen mustard mechlorethamine HCl at a concentration of 0.02% in six topical formulations: Aquaphor ointment, Transcutol, Labrasol, 10% Transcutol in Aquaphor, 10% Transcutol in Labrasol, and Aquaphilic ointment. The drug decomposed gradually in Aquaphor ointment at room temperature, dropping to 95% in 4 weeks, 85% in 12 weeks, and 78% in 39 weeks. On the other hand, the drug decomposed rapidly in Aquaphilic ointment, giving an assay of less than 20% of its initial concentration after 24h at room temperature. Generally, mechlorethamine HCl was more stable in Aquaphor ointment than in formulations containing Transcutol or Labrasol. However, the addition of the free radical inhibitor, BHT, significantly enhanced the stability of mechlorethamine in Transcutol and Labrasol formulations. Four BHT-stabilized Transcutol and Labrasol formulations gave assays in ranges of 92-99% at the end of 4 weeks, 77-98% at the end of 12 weeks, and 38-93% at the end of 41 weeks.