Brompton mixture has been widely used for cancer patients to control pain.This mixture originally consists of morphine HCl, cocaine HCl, simple syrup, ethyl alcohol, chloroform and water.In Japan, chloroform is omitted and ethyl alcohol is occasionally removed from the original prescription.Because this mixture is a medicine for cancer patients, great attention should be paid to microbial contamination.But it has not been investigated on the preservative efficacy of Brompton mixture, yet. Thus, the preservative efficacy of Brompton mixture was studied.
Brompton mixtures with various compositions were challenged with 1×10⁶ cells/ml each of Staphylococcus aureus, Escherichia coli or Pseudomonas aeruginosa or 1×10⁵ cells/ml of Candida albicans or 1×10⁵ spores/ml of Aspergillus niger. Samples were taken on day 1, 2, 7, 14 and 28 during storage at 25°C for determining viable counts of the organisms.The preservative efficacy of Brompton mixture was assessed by a slightly modified British Pharmacopoeia (B. P.) standard;The number of S. aureus, E.coli and P. aeruginosa recovered per ml is reduced by less than 10³ within forty-eight hours of challenge, and there is no increase thereafter. The number of C. albicans recovered per ml is reduced by less than 10² within fourteen days of challenge, and there is no increase thereafter. In the case of A.niger, there is no budding of spores during twenty-eight days of challenge.
The modified B. P. standard was achieved by Brompton mixtures containing ethyl alcohol at concentrations above 8%, but not by mixtures containing no or less than 5% of ethyl alcohol. Then, the effect of preservative agents, parahydroxybenzoates on these inadequately preserved mixtures was studied.The modified B.P.standard was achieved by mixtures with 0.06% methylparaben, 0.03% ethylparaben and 0.01% propylparaben, but not 0.05% ethylparaben or 0.09% methylparaben and 0.01% propylparaben.
It is desire that Brompton mixtures containing no or less than 5% ethyl alcohol should include 0.06% methylparaben, 0.03% ethylparaben and 0.01% propylparaben for protecting microbial contamination.