Adalimumab Formulation Stability at Elevated Temperatures
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Solution Overview
Problem
Existing formulations of adalimumab, a TNFα inhibitor, face stability issues when stored at elevated temperatures, leading to increased levels of acidic species and high molecular weight aggregates, which can impact the drug's potency and shelf-life.
Innovation Solution
A stable aqueous adalimumab formulation is developed, comprising 180 mg/mL adalimumab, 20 mM glutamate, and 160 mM monoethanolamine, with a pH of 5.2, which demonstrates less than a 2.1-fold increase in acidic species after 28 days at 40°C, as measured by cation-exchange HPLC.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If adalimumab is stored at elevated temperatures, then the storage duration is extended, but the stability of the formulation deteriorates leading to increased acidic species and aggregates
Solution Approach 1:
The patent applies parameter changes by optimizing the pH to 5.2 and adjusting the concentrations of glutamate (20 mM) and monoethanolamine (160 mM) to achieve enhanced thermal stability. These specific parameter adjustments prevent the formation of acidic species and aggregates during elevated temperature storage, resolving the contradiction between extended shelf-life and maintained formulation stability.
2Quantity of substance
If the concentration of adalimumab is increased to 180 mg/mL, then the potency per volume is improved, but the formulation stability deteriorates due to increased aggregation
Solution Approach 1:
The patent uses parameter changes by setting the pH to 5.2 and optimizing the buffer system composition (glutamate and monoethanolamine concentrations) to stabilize adalimumab at the high concentration of 180 mg/mL. These parameter adjustments prevent aggregation despite the increased protein concentration, allowing high potency while maintaining formulation stability.
3Ease of manufacture
If conventional formulations are used, then the manufacturing process is simple, but the shelf-life is limited due to instability at elevated temperatures
Solution Approach 1:
The patent applies parameter changes by optimizing pH to 5.2 and adjusting buffer concentrations to achieve enhanced thermal stability without complicating the manufacturing process. The formulation maintains simplicity while extending shelf-life through these targeted parameter optimizations that prevent degradation during storage.
Data Source
AI summary
Stable adalimumab formulations are disclosed.