Hexanedioic Acid Buffer Modulates Biopharmaceutical Immunogenicity
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Solution Overview
Problem
Biopharmaceuticals administered subcutaneously often induce unwanted immunogenicity, leading to increased costs, reduced bioavailability, and potential life-threatening reactions due to their antigenic properties, which existing formulations like those containing citric acid fail to adequately address.
Innovation Solution
The use of hexanedioic acid or its salts in place of citric acid in pharmaceutical formulations for anti-TNFα antibodies, combined with stabilizers such as amino acids, sugar polyols, and disaccharides, to reduce immunogenicity and improve bioavailability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If subcutaneous administration is used for biopharmaceuticals, then patient self-administration and reduced invasiveness are achieved, but unwanted immunogenicity and reduced bioavailability occur
Solution Approach 1:
The patent modifies the chemical composition parameters of the formulation by incorporating specific excipients and buffer systems that reduce immunogenicity, thereby improving bioavailability while maintaining the subcutaneous administration route
Solution Approach 2:
The patent introduces intermediary substances (excipients, stabilizers, and buffer components) that mediate between the biopharmaceutical and the immune system, reducing unwanted immune responses and improving drug absorption
2Ease of operation
If subcutaneous administration is used for biopharmaceuticals, then patient self-administration is enabled, but increased clearance and reduced efficacy occur
Solution Approach 1:
The formulation parameters are optimized by adjusting pH, ionic strength, and composition to reduce clearance rates and extend the duration of therapeutic action
Solution Approach 2:
The patent incorporates protective excipients and stabilizers that cushion the biopharmaceutical against premature clearance and degradation, ensuring sustained efficacy
3Reliability
If citric acid is used in formulations, then immune response modulation is achieved, but skin irritation and pain at injection site occur
Solution Approach 1:
The patent removes or reduces citric acid from the formulation and replaces it with alternative buffer systems that do not cause skin irritation, while maintaining immune response modulation capabilities
Solution Approach 2:
The patent uses alternative excipients that are less irritating to the skin, sacrificing the immunomodulatory benefits of citric acid for reduced local adverse effects
Data Source
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AI summary
The present invention is related to methods of preparing a pharmaceutical formulation comprising a biopharmaceutical drug, which methods allows the modulation of immune responses related to the administration thereof. The formulation comprises a buffer comprising hexanedioic acid or at least one salt thereof, and/or citric acid or at least one salt thereof. The present invention further relates to method of using hexanedioic acid or at least one salt thereof, and/or citric acid or at least one salt thereof, to modulate the immunogenicity of a pharmaceutical formulation, to a pharmaceutical formulation as such, and to methods of modulating or determining immune responses related to the administration of a pharmaceutical formulation (Fig. 4).