A Formulation Development Approach to Identify and Select Stable Ultra–High-Concentration Monoclonal Antibody Formulations With Reduced Viscosities
| Autor: | C. Russell Middaugh, Jian Xiong, Samantha E. Pace, David B. Volkin, Sangeeta B. Joshi, Neal Whitaker, Vineet Kumar |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
High concentration
Chromatography Protein Stability Viscosity Chemistry medicine.drug_class Drug Compounding High protein Antibodies Monoclonal Pharmaceutical Science Excipient 02 engineering and technology Pharmaceutical formulation 021001 nanoscience & nanotechnology Monoclonal antibody 030226 pharmacology & pharmacy Excipients 03 medical and health sciences 0302 clinical medicine Drug Stability medicine Humans 0210 nano-technology medicine.drug |
| Zdroj: | Journal of Pharmaceutical Sciences. 106:3230-3241 |
| ISSN: | 0022-3549 |
| DOI: | 10.1016/j.xphs.2017.06.017 |
| Popis: | High protein concentration formulations are required for low-volume administration of therapeutic antibodies targeted for subcutaneous, self-administration by patients. Ultra-high concentrations (≥150 mg/mL) can lead to dramatically increased solution viscosities, which in turn can lead to stability, manufacturing, and delivery challenges. In this study, various categories and individual types of pharmaceutical excipients and other additives (56 in total) were screened for their viscosity reducing effects on 2 different mAbs. The physicochemical stability profile, as well as viscosity ranges, of several candidate antibody formulations, identified and designed based on the results of the excipient screening, were evaluated over a 6-month time period under accelerated and real-time storage conditions. In addition to reducing the solution viscosities to acceptable levels for parenteral administration (using currently available and acceptable delivery devices), the candidate formulations did not result in notable losses of physicochemical stability of the 2 antibodies on storage for 6 months at 25°C. The experiments described here demonstrate the feasibility of a formulation development and selection approach to identify candidate high-concentration antibody formulations with viscosities within pharmaceutically acceptable ranges that do not adversely affect their physicochemical storage stability. |
| Databáze: | OpenAIRE |
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