Improved formulation and lyophilization cycle for rBCG vaccine

Jin, Tom H.; Nguyen, Lisa; Qu, Tianli; Tsao, Eric

doi:10.1016/j.vaccine.2011.04.056

Cited by 19 publications

(17 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…So, though mechanical properties such as modulus and strength have been measured for cellular materials manufactured by freeze‐drying, there have been no detailed attempts to optimize and understand the lyophilization process using such data sets. For example, such a quantitative approach would have benefited the recent work on the Bacillus Calmette–Guérin vaccine . Traditional formulations resulted in a crumbed FD powder, which was deemed unacceptable as a final product.…”

Section: Introductionmentioning

confidence: 99%

“…Traditional formulations resulted in a crumbed FD powder, which was deemed unacceptable as a final product. A new formulation using mannitol and sucrose was designed which was assessed as “having better cake appearance” . However, no reference was made to mechanical properties of this new cake formulation to indicate its susceptibility to breakage as a comparison, though visually it was vastly superior to the old formulation.…”

Section: Introductionmentioning

confidence: 99%

“…For example, such a quantitative approach would have benefited the recent work on the Bacillus Calmette-Guérin vaccine. 59 Traditional formulations resulted in a crumbed FD powder, which was deemed unacceptable as a final product. A new formulation using mannitol and sucrose was designed which was assessed as "having better cake appearance".…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Morphological and Compressional Mechanical Properties of Freeze-Dried Mannitol, Sucrose, and Trehalose Cakes

Devi

2013

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Morphological and Compressional Mechanical Properties of Freeze-Dried Mannitol, Sucrose, and Trehalose Cakes

Devi

2013

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

“…Sodium glutamate is a potent stabilizer used in freeze-dried vaccine formulations. 43) Some protein-rich mixture frozen solutions showed sharp single T g ′ transition peak that shifted depending on the solute mass ratio. Contrarily, frozen solutions containing a higher mass ratio of Na·L-Glu showed broad transitions that have a peak at temperatures close to T g ′ of the singlesolute frozen Na·L-Glu solution in the derivative DSC curves.…”

Section: Resultsmentioning

confidence: 99%

Amorphous–Amorphous Phase Separation of Freeze-Concentrated Protein and Amino Acid Excipients for Lyophilized Formulations

Izutsu¹,

Yoshida²,

Shibata³

et al. 2016

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

The objective of this study was to elucidate the mixing state of proteins and amino acid excipients concentrated in the amorphous non-ice region of frozen solutions. Thermal analysis of frozen aqueous solutions was performed in heating scans before and after a heat treatment. Frozen aqueous solutions containing a protein (e.g., recombinant human albumin, gelatin) or a polysaccharide (dextran) and an amino acid excipient (e.g., L-arginine, L-arginine hydrochloride, L-arginine monophosphate, sodium L-glutamate) at varied mass ratios showed single or double T g ′ (glass transition temperature of maximally freeze-concentrated solutes). Some mixture frozen solutions rich in the polymers maintained the single T g ′ of the freeze-concentrated amorphous solute-mixture phase. In contrast, amino acid-rich mixture frozen solutions revealed two T g ′s that suggested transition of concentrated non-crystalline solute-mixture phase and excipient-dominant phase. Post-freeze heat treatment induced splitting of the T g ′ in some intermediate mass ratio mixture solutions. The mixing state of proteins and amino acids varied depending on their structure, salt types, mass ratio, composition of co-solutes (e.g., NaCl) and thermal history. Information on the varied mixing states should be valuable for the rational use of amino acid excipients in lyophilized protein pharmaceuticals.Key words amorphous; freeze drying; thermal analysis; protein formulation; stabilization; mixing Freeze-drying is a popular method to formulate therapeutic proteins that are insufficiently stable in aqueous solutions during storage.1) Several freeze-dried therapeutic protein formulations contain multiple excipients, including stabilizers, bulking agents, pH buffer agents, and tonicity modifiers besides active pharmaceutical ingredient (API).2-4) Sucrose and trehalose are popular stabilizers that protect proteins from dehydration-induced irreversible structural changes during the process and from chemical degradation during storage. Certain amino acids and their salts are potent stabilizers in the freeze-drying of proteins, frozen storage of liposomes, and spray drying of vaccines.5-11) Application of the amino acid excipients that protect proteins through particular mechanisms not achievable by saccharides (e.g., aggregation-reducing effect of L-arginine (L-Arg) in aqueous solution) would increase formulation strategies in lyophilization of marginally stable proteins. 5,8,[12][13][14][15] Physical states (e.g., crystallinity, crystal polymorph) of the components are important factors that determine chemical and conformational stability of proteins during the freeze-drying process and subsequent storage. [16][17][18] The stabilizing effects of disaccharides are attributed to protection of protein conformation by the substitution of surrounding water molecules and by holding protein molecules in lower molecular mobility glassstate amorphous solids. Crystallization of some sugar alcohols (e.g., mannitol) during the freezing segment of lyophilization deprives the...

show abstract

“…Dr. Eric Tsao described some of the critical issues involving the manufacture of dry powder vaccines, and the benefits of dry powder formulation [47,48]. At Aeras, dry powder adenovirus TB vaccines have been produced using a spray dying process that results in free flowing, non-hygroscopic particles with a size range of 1 to 5 m [49].…”

Section: Dry Powder Aerosol Vaccines For Tuberculosis: Opportunities mentioning

confidence: 99%

Developing aerosol vaccines for Mycobacterium tuberculosis: Workshop proceedings

Achkar¹,

Beverley²,

Boom³

et al. 2015

Vaccine

View full text Add to dashboard Cite

On April 9, 2014, Aeras and the National Institute of Allergy and Infectious Diseases convened a workshop entitled "Developing Aerosol Vaccines for Mycobacterium tuberculosis" in Bethesda, MD. The purpose of the meeting was to explore the potential for developing aerosol vaccines capable of preventing infection with M. tuberculosis (Mtb), preventing the development of active tuberculosis (TB) among those latently infected with Mtb, or as immunotherapy for persons with active TB. The workshop was organized around four key questions relevant to developing and assessing aerosol TB vaccines: (1) What is the current knowledge about lung immune responses and early pathogenesis resulting after Mtb infection and what are the implications for aerosol TB vaccine strategies? (2) What are the technical issues surrounding aerosol vaccine delivery? (3) What is the current experience in aerosol TB vaccine development? and (4) What are the regulatory implications of developing aerosol vaccines, including those for TB? Lessons learned from the WHO effort to develop an aerosol measles vaccine served as a case example for overall discussions at the meeting. Workshop participants agreed that aerosol delivery represents a potentially important strategy in advancing TB vaccine development efforts. As no major regulatory, manufacturing or clinical impediments were identified, members of the workshop emphasized the need for greater support to further explore the potential for this delivery methodology, either alone or as an adjunct to traditional parenteral methods of vaccine administration.

show abstract

Improved formulation and lyophilization cycle for rBCG vaccine

Cited by 19 publications

References 22 publications

Morphological and Compressional Mechanical Properties of Freeze-Dried Mannitol, Sucrose, and Trehalose Cakes

Morphological and Compressional Mechanical Properties of Freeze-Dried Mannitol, Sucrose, and Trehalose Cakes

Amorphous–Amorphous Phase Separation of Freeze-Concentrated Protein and Amino Acid Excipients for Lyophilized Formulations

Developing aerosol vaccines for Mycobacterium tuberculosis: Workshop proceedings

Contact Info

Product

Resources

About