Back to Search
Start Over
Hepatitis-B surface antigen (HBsAg) powder formulation: process and stability assessment.
- Source :
-
Current drug delivery [Curr Drug Deliv] 2007 Jan; Vol. 4 (1), pp. 57-67. - Publication Year :
- 2007
-
Abstract
- The purpose of this study was to develop a hepatitis-B surface antigen (HBsAg) dry powder vaccine formulation suitable for epidermal powder immunization (EPI) via an efficient, scalable powder-formation process. Several HBsAg dry powder formulations were prepared using four different powder-formation methods: freeze-drying/compress/grind/sieve (FD/C/G/S), spray-drying (SD), agarose beads, and spray freeze-drying (SFD). Powder properties and physical stability were determined using particle size analysis, tap density measurement, scanning electron microscopy, optical microscopy, and moisture content analysis. Physical, chemical and biochemical stability of HBsAg was determined by dynamic light scattering, an enzyme immune assay, and immunogenicity in a mouse or hairless guinea pig model. Out of the four powder-formation methods evaluated SFD outperformed other methods in the following considerations: good process efficiency, flexible scalability, and desirable particle characteristics for skin penetration. The stress posed by SFD appeared to be mild as HBsAg in the dry form retained its potency and immunogenicity. Notably, the mechanism of fast freezing by SFD actually promoted the preservation of HBsAg nanoparticle size, in good correlation with long-term biochemical stability. Among several formulations screened, the formulation containing 10 microg HBsAg in 1-mg powder with a tertiary mixture of trehalose, mannitol, and dextran, exhibited excellent overall stability performance. In conclusion, HBsAg dry powder formulations suitable for EPI were successfully prepared using SFD. Further, a systematic formulation development strategy allowed the development and optimization of an HBsAg dry powder formulation, demonstrating excellent long-term physical, biochemical, and immunological stability.
- Subjects :
- Administration, Cutaneous
Animals
Disaccharides chemistry
Drug Stability
Excipients chemistry
Female
Guinea Pigs
Hepatitis B Surface Antigens genetics
Hepatitis B Vaccines administration & dosage
Hepatitis B Vaccines immunology
Immunization methods
Immunoenzyme Techniques methods
Injections, Intramuscular
Lysine chemistry
Mice
Mice, Inbred BALB C
Microscopy, Electron, Scanning
Microspheres
Nanoparticles chemistry
Particle Size
Poloxamer chemistry
Powders
Sepharose chemistry
Hepatitis B Surface Antigens immunology
Hepatitis B Vaccines chemistry
Technology, Pharmaceutical methods
Subjects
Details
- Language :
- English
- ISSN :
- 1567-2018
- Volume :
- 4
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Current drug delivery
- Publication Type :
- Academic Journal
- Accession number :
- 17269918
- Full Text :
- https://doi.org/10.2174/156720107779314758