Development of a multidose formulation for a humanized monoclonal antibody using experimental design techniques
Journal Title: The AAPS Journal - Year 2003, Vol 5, Issue 2
Abstract
The purpose of this study was to identify optimal preservatives for a multidose formulation of a humanized monoclonal antibody using experimental design techniques. The effect of antimicrobial parenteral preservatives (benzyl alcohol, chlorobutanol, methyl paraben, propylparaben, phenol, and m-cresol) on protein stability was assessed using size-exclusion chromatography, differential scanning calorimetry, right-angle light scattering, UV spectroscopy, and potency testing using a cell-based fluorescence-activated cell sorting method. A quick, cost-effective preservative screening test was designed. Combinations of preservatives were examined using an I-optimal experimental design. The protein was most stable in the presence of methylparaben and propylparaben, and was compatible with benzyl alcohol and chlorobutanol at low concentrations. Phenol and m-cresol were not compatible with the protein. The I-optimal experimental design indicated that as an individual preservative, benzyl alcohol was promising. The model also indicated several effective combinations of preservatives that satisfied the antimicrobial efficacy and physical stability constraints. The preservative screening test and the experimental design approach were effective in identifying optimal concentrations of antimicrobial preservatives for a multidose protein formulation; (1) benzyl alcohol, and (2) the combination of methylparaben and chlorobutanol were screened as potential candidates to satisfy the regulatory requirements of various preservative efficacy tests.
Authors and Affiliations
Supriya Gupta, Elizabet Kaisheva
Keywords
Related Articles
- EP ID EP681966
- DOI 10.1208/ps050208
- Views 69
- Downloads 0
Cationic Liposomes Loaded with a Synthetic Long Peptide and Poly(I:C): a Defined Adjuvanted Vaccine for Induction of Antigen-Specific T Cell Cytotoxicity
The online version of this article (doi:10.1208/s12248-014-9686-4) contains supplementary material, which is available to authorized users.
Design and Evaluation of a PEGylated Lipopeptide Equipped with Drug-Interactive Motifs as an Improved Drug Carrier
The online version of this article (doi:10.1208/s12248-013-9536-9) contains supplementary material, which is available to authorized users.
Microencapsulation of hemoglobin in chitosan-coated alginate microspheres prepared by emulsification/internal gelation
Chitosan-coated alginate microspheres prepared by emulsification/internal gelation were chosen as carriers for a model protein, hemoglobin (Hb), owing to nontoxicity of the polymers and mild conditions of the method. The...
Pancreatic Cancer: Pathobiology, Treatment Options, and Drug Delivery
Pancreatic cancer is the fourth leading cause of cancer-related deaths in the USA. The high mortality rate is partly due to lack of effective treatments. This review summarizes the pathobiology and current treatment opti...
k Opioids as potential treatments for stimulant dependence
Stimulant abuse is a major problem in the United States and the development of pharmacological treatments for stimulant abuse remains an important therapeutic goal. Classically, the “dopamine hypothesis”...