Stability study of measles, mumps, rubella and varicella combined live attenuated vaccine with different stabilizer formulations

Objective To compare the stability of measles, mumps, rubella and varicella combined live attenuated vaccine (MMRV) using different lyophilization stabilizer formulations, and to select the optimal formulation. Methods The effects of 2 lyophilization stabilizers with gelatin (formulas 1, 2) and 1 without (formula 3) on moisture and virus titers of MMRV stored at 37, 25 and 2-8 ℃were compared. Results In the 37 ℃ accelerated stability test, only formula 3 MMRV had all 4 virus titers within the required range. In the 25 ℃ accelerated stability test, at 1 month, the mumps and varicella virus titers in formula 1 MMRV were below the lower limit (4.6 lg 50% cell culture infective dose/ml and 3.7 lg plaque-forming unit/ml, respectively). All virus titers in formulas 2 and 3 MMRV at 6 months were within the required range, although mumps and varicella virus titers in formula 2 MMRV were at the lower limit. In 2-8 ℃ long-term stability test, the mumps and vericella virus titers in formula 1 MMRV at 6 months were all below the lower limit. The stabilities of formulas 2 and 3 MMRV were qualified for up to 18 and 24 months, respectively. Conclusions The formula 3 gelatin-free lyophilization stabilizer developed for MMRV has the best protective effect on all 4 viruses during lyophilization and preservation processes. The period of validity for formula 3 MMRV is at least 2 years. Key words: Vaccines, combined; Freeze drying; Excipients; Drug stability