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Improved formulation and lyophilization cycle for rBCG vaccine.
Vaccine 2011; 29(29-30):4848-52V

Abstract

To improve the conventional BCG vaccine in cake appearance and integrity, a new formulation with corresponding freeze drying cycle was developed for a recombinant BCG vaccine. The new formulation contains mannitol as a bulking agent, and trehalose, sucrose and sodium glutamate as stabilizers. The formulation and freeze drying cycle were tested with different super cooling rates and secondary drying temperatures, with or without an annealing process. Thermodynamic behavior was characterized using differential scanning calorimetry (DSC). Varying the secondary drying temperature and presence/absence of an annealing step caused marked differences in cake thermodynamic profiles irrespective of different cooling rates. The annealing process allowed efficient crystallization of the mannitol. Failure to crystallize the bulking agent had the potential to depress the Tg' and compromise storage stability in the final lyophile by crystallizing from the solid during storage, even when the secondary drying temperature was as high as 40°C. The improved formulation and freeze drying cycle resulted in good recovery of 53.2% during lyophilization and a higher survival rate of 61.7% in an accelerated stability study than the conventional BCG formulation and cycle. In summary, full crystallization was necessary for the mannitol bulking formulation. The freeze dried rBCG vials obtained using the formulation and drying cycle developed here met the requirements of BCG vaccine in good cake appearance, high viability post freeze drying and heat stability during storage.

Authors+Show Affiliations

Aeras, 1405 Research Blvd, Suite 300, Rockville, MD 20850, USA. zjin@aeras.orgNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21549782

Citation

Jin, Tom H., et al. "Improved Formulation and Lyophilization Cycle for rBCG Vaccine." Vaccine, vol. 29, no. 29-30, 2011, pp. 4848-52.
Jin TH, Nguyen L, Qu T, et al. Improved formulation and lyophilization cycle for rBCG vaccine. Vaccine. 2011;29(29-30):4848-52.
Jin, T. H., Nguyen, L., Qu, T., & Tsao, E. (2011). Improved formulation and lyophilization cycle for rBCG vaccine. Vaccine, 29(29-30), pp. 4848-52. doi:10.1016/j.vaccine.2011.04.056.
Jin TH, et al. Improved Formulation and Lyophilization Cycle for rBCG Vaccine. Vaccine. 2011 Jun 24;29(29-30):4848-52. PubMed PMID: 21549782.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Improved formulation and lyophilization cycle for rBCG vaccine. AU - Jin,Tom H, AU - Nguyen,Lisa, AU - Qu,Tianli, AU - Tsao,Eric, Y1 - 2011/05/05/ PY - 2011/03/17/received PY - 2011/04/13/revised PY - 2011/04/16/accepted PY - 2011/5/10/entrez PY - 2011/5/10/pubmed PY - 2011/9/29/medline SP - 4848 EP - 52 JF - Vaccine JO - Vaccine VL - 29 IS - 29-30 N2 - To improve the conventional BCG vaccine in cake appearance and integrity, a new formulation with corresponding freeze drying cycle was developed for a recombinant BCG vaccine. The new formulation contains mannitol as a bulking agent, and trehalose, sucrose and sodium glutamate as stabilizers. The formulation and freeze drying cycle were tested with different super cooling rates and secondary drying temperatures, with or without an annealing process. Thermodynamic behavior was characterized using differential scanning calorimetry (DSC). Varying the secondary drying temperature and presence/absence of an annealing step caused marked differences in cake thermodynamic profiles irrespective of different cooling rates. The annealing process allowed efficient crystallization of the mannitol. Failure to crystallize the bulking agent had the potential to depress the Tg' and compromise storage stability in the final lyophile by crystallizing from the solid during storage, even when the secondary drying temperature was as high as 40°C. The improved formulation and freeze drying cycle resulted in good recovery of 53.2% during lyophilization and a higher survival rate of 61.7% in an accelerated stability study than the conventional BCG formulation and cycle. In summary, full crystallization was necessary for the mannitol bulking formulation. The freeze dried rBCG vials obtained using the formulation and drying cycle developed here met the requirements of BCG vaccine in good cake appearance, high viability post freeze drying and heat stability during storage. SN - 1873-2518 UR - https://www.unboundmedicine.com/medline/citation/21549782/Improved_formulation_and_lyophilization_cycle_for_rBCG_vaccine_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0264-410X(11)00601-3 DB - PRIME DP - Unbound Medicine ER -