title: Stabilization of tetanus toxoid formulation containing aluminium hydroxide adjuvant against agitation.
abstract: The aggregation of tetanus toxoid leads to reduced bioavailability of the vaccine and failure of immunization programmes in many parts of the globe. One of the main reasons for denaturation and aggregation of tetanus toxoid formulations is agitation of the protein during transport. We have identified that agitation leads to collapse of the gel matrix of aluminium hydroxide which is used as an adjuvant in these preparations. This results in desorption of the toxoid from the matrix, which then loses its antigenicity due to agitation-induced denaturation of the protein. We show that incorporation of some compatible osmolytes like sorbitol, glucose and arginine, but not trehalose, is able to protect the adjuvant matrix from degradation, and retain the integrity of the vaccine preparation in terms of its antigenicity.
authors.affiliation: Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Sector 67, SAS Nagar, Punjab 160062, India.
authors.forename: Vipul A
authors.initials: VA
authors.lastname: Solanki
authors.forename: Nishant K
authors.initials: NK
authors.lastname: Jain
authors.forename: Ipsita
authors.initials: I
authors.lastname: Roy
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry*; D000327:Adsorption; D000536:Aluminum Hydroxide / Q000737:chemistry* / Q000276:immunology; D001120:Arginine / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding; D004355:Drug Stability; D004797:Enzyme-Linked Immunosorbent Assay; D005079:Excipients / Q000737:chemistry; D005782:Gels; D005947:Glucose / Q000737:chemistry; D011489:Protein Denaturation; D055550:Protein Stability; D013012:Sorbitol / Q000737:chemistry; D013314:Stress, Mechanical; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods; D013745:Tetanus Toxoid / Q000737:chemistry* / Q000276:immunology; D014199:Trehalose / Q000737:chemistry
chemical_list: D000276:Adjuvants, Immunologic; D005079:Excipients; D005782:Gels; D013745:Tetanus Toxoid; D013012:Sorbitol; D000536:Aluminum Hydroxide; D001120:Arginine; D014199:Trehalose; D005947:Glucose