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Design and Optimization of a Temperature-Stable Dry Powder BCG Vaccine.
- Source :
-
Pharmaceutical research [Pharm Res] 2019 Dec 23; Vol. 37 (1), pp. 11. Date of Electronic Publication: 2019 Dec 23. - Publication Year :
- 2019
-
Abstract
- Purpose: Loss of vaccine potency due to extreme temperature exposure during storage and transport remains a significant obstacle to the success of many vaccines, including the Bacille Calmette-Guérin (BCG) vaccine, the only vaccine available against Mycobacterium tuberculosis. BCG is a live, attenuated vaccine requiring refrigerated storage for viability. In this study, we formulated a temperature-stable BCG dry powder using the spray drying technique.<br />Methods: We employed a factorial design to optimize our formulation of stabilizing excipients that included L-leucine, bovine serum albumin, polyvinylpyrrolidone, mannitol, and trehalose. Powders were characterized for their particle size, yield, water retention and uptake, glass transition temperature, and aerosol performance. Three optimal powder carrier mixtures were selected from the factorial design for BCG incorporation based on their stability-promoting and powder flow characteristics. Vaccine powders were also assessed for BCG viability and in vivo immunogenicity after long-term storage.<br />Results: Live BCG was successfully spray-dried using the optimized carriers. Dry powder BCG showed no loss in viability (25°C, up to 60% relative humidity; RH) and ~2-log loss in viability (40°C, 75% RH) after one year of storage. The aerodynamic size of the powders was in the respirable range. Further, when healthy mice were immunized intradermally with reconstituted BCG powders (storage for 2 years), the vaccine retained its immunogenicity.<br />Conclusion: We developed a spray-dried BCG vaccine that was viable and antigenic after long-term storage. To our knowledge, this is a first study to show room temperature stability of live BCG vaccine without any loss in viability for 12 months.
- Subjects :
- Aerosols chemistry
Animals
Cell Line
Cell Survival
Desiccation methods
Drug Stability
Drug Storage
Female
Humans
Leucine chemistry
Mannitol chemistry
Mice, Inbred C57BL
Mycobacterium bovis cytology
Povidone chemistry
Serum Albumin, Bovine chemistry
Temperature
Tissue Distribution
Trehalose chemistry
BCG Vaccine chemistry
BCG Vaccine pharmacology
Drug Compounding methods
Excipients chemistry
Powders chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1573-904X
- Volume :
- 37
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Pharmaceutical research
- Publication Type :
- Academic Journal
- Accession number :
- 31873825
- Full Text :
- https://doi.org/10.1007/s11095-019-2739-8