High-Concentration Anti-IL-23p19 Formulation for Stable 1 mL Injection
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Solution Overview
Problem
Existing pharmaceutical formulations of high-concentration anti-IL-23p19 antibodies, such as risankizumab, face stability issues with aggregation and increased viscosity, making them unsuitable for subcutaneous injection, which is necessary for chronic conditions like psoriasis.
Innovation Solution
A stable liquid formulation comprising 150 mg/ml of anti-IL-23p19 antibody risankizumab, including components like polyols, surfactants, and optionally buffers, with a pH of 5.5-5.9, ensuring isotonicity and suitable viscosity for single-injection administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If the antibody concentration is increased to 150 mg/ml, then the injection volume is reduced to 1 ml for a 150 mg dose, but the formulation becomes unstable with aggregation and increased viscosity
Solution Approach 1:
The patent applies parameter changes by systematically optimizing multiple formulation parameters including pH (set to 5.5-5.9), ionic strength, presence of excipients (polyols, surfactants, buffers), and oxidation-reduction potential. These parameter adjustments enable the formulation to maintain stability at the high antibody concentration of 150 mg/ml while preventing aggregation and controlling viscosity, thus resolving the contradiction between concentration and stability.
2Quantity of substance
If the antibody concentration is increased to 150 mg/ml, then the injection volume is reduced to 1 ml for a 150 mg dose, but the viscosity increases making injection difficult
Solution Approach 1:
The patent controls viscosity by adjusting formulation parameters including pH, ionic strength, and the addition of specific excipients. These changes enable the high-concentration formulation to maintain suitable viscosity characteristics for subcutaneous injection, resolving the contradiction between concentration and injection ease.
3Quantity of substance
If multiple injections are used for high volumes, then the total dose can be administered, but patient adherence decreases and attrition rate increases
Solution Approach 1:
The patent merges the entire 150 mg dose into a single 1 ml injection volume by achieving high antibody concentration (150 mg/ml) in a stable formulation. This consolidation eliminates the need for multiple injections, thereby improving patient adherence and reducing attrition rates while maintaining the required total dose delivery.
Data Source
AI summary
The present disclosure inter alia provides a liquid pharmaceutical formulation comprisinga) 150 mg/ml of an anti-IL-23p19 antibody, wherein the antibody comprises a light chain amino acid sequence according to SEQ ID NO: 1 and a heavy chain amino acid sequence according to SEQ ID NO: 2;b) a polyol; andc) a surfactant.The disclosed high concentration formulations are advantageously storage stable and suitable for subcutaneous administration.