ABSTRACT
To predict the self-life of the lyophilized BCG during accelerated stability study. Bacillus Calmette and Guerin [BCG] has been commonly known as an anti tuberculosis vaccine since its first introduction in Paris by Calmette and Guerin. Later it was discovered as an important immunotherapeutic agent for treatment of superficial bladder cancer. Only two internationally freeze dried BCG products are approved for bladder cancer treatment worldwide due to several restrictions in WHO guidelines. Other manufactures can only distribute their BCG products in their local markets. BCG was suspended into three stabilizer systems containing 15% w/v trehalose, trehalose-gelatin mixture [in ratio, 30:1 w/w] or lactose. The prepared formulae were lyophilized and the lyophilized formulae were stored at 5 degree C, 60% RH for the accelerated study. Scheduled pulling out of samples to test their viabilities was performed according to a stability plan. Shelf-life of each formula was estimated using Q10 method. Lactose as a stabilizer was found to be superior over trehalose or trehalosegelatin mixture. Shelf life estimates using Q10 method were about 330 days with Trehalose, 176 days with Trehalose-gelatin and more than two years with lactose compared with 100 days for liquid BCG-T. Lactose was unique in extending the shelf approximately double the period that was attainable with Trehalose. Meanwhile, Trehalose-gelatin mixture appeared to be the lowest in BCG protection
Subject(s)
BCG Vaccine , Freeze Drying , Antineoplastic Agents , Drug StabilityABSTRACT
The aim of the present study was to evaluate the possible immunomodulatory effects of dimethy1-4,4-dimethoxy-5,6,5',6'-dimethylene dioxy biphenyl-2,2'-dicarboxylate [DDB] through basic immunological parameters. To achieve this goal, mice were daily treated for either one or four weeks with two dose levels, 6 or 60 mg/kg. The following results were obtained: the body weight and relative weights of liver and spleen were not affected while, the relative thymus weight showed transient increase following administration of the lower dose for one week. Administration of DDB has also resulted in significant increase in the efficiency of phagocytosis and serum level of immunoglobulins. This increase was not affected by alteration of dose level and duration of administration in case of phagocytosis and IgG while IgM was slightly affected. The total leukocytic count showed a dose-dependent increase following the four week administration. Administration of DDB for one week resulted in slight changes in the differential leukocytic count, which were disappeared in the four week regimen. The count of bone marrow lymphocytes was decreased by administration of the lower dose for one week and increased by administration of both doses for four weeks. On the offer hand, the viability of these cells was increased only by administration of the higher dose for four weeks. Exposure to DDB in presence of experimentally induced acute bacterial hepatic injury was found to elicit significant protection against the infection-caused body weight loss and the rise in serum IgG and ALT levels. The obtained results show that DDB has a clear immunomodulatory potential