Antisense Oligonucleotide Viscosity and Turbidity Control
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Solution Overview
Problem
Current antisense oligonucleotide solutions face challenges with high viscosity and turbidity, which hinder their effective manufacture, storage, administration, and delivery, particularly at high concentrations.
Innovation Solution
The use of specific excipients that modulate viscosity and turbidity, such as aromatic and heterocyclic compounds, to create aqueous solutions with reduced dynamic viscosity and turbidity, ensuring the antisense oligonucleotides are effective at concentrations ranging from 1 mg/mL to 500 mg/mL.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If antisense oligonucleotide concentration is increased to improve therapeutic efficacy, then the concentration of active ingredient increases, but viscosity increases making administration difficult
Solution Approach 1:
A viscosity-reducing excipient is introduced as an intermediary substance that interacts with the antisense oligonucleotide solution to reduce its viscosity. This mediator allows high concentrations of the active ingredient to be maintained while restoring administrable flow characteristics to the formulation.
Solution Approach 2:
The physical parameter of viscosity is actively modified by adding the excipient, changing the rheological properties of the antisense oligonucleotide solution. This parameter change enables the formulation to maintain both high drug concentration and appropriate viscosity for injection or other administration routes.
2Quantity of substance
If antisense oligonucleotide concentration is increased to improve therapeutic efficacy, then the concentration of active ingredient increases, but turbidity increases affecting product quality
Solution Approach 1:
The excipient acts as a intermediary that modifies the optical properties of the high-concentration antisense oligonucleotide solution, reducing turbidity while allowing the high active ingredient concentration necessary for therapeutic efficacy to be maintained.
3Ease of operation
If viscosity-reducing excipient is added to improve administration ease, then viscosity decreases facilitating delivery, but formulation complexity increases
Solution Approach 1:
Rather than complicating the delivery device or administration system, the solution modifies the fundamental physical parameter of the formulation itself (viscosity) by adding an excipient. This approach simplifies the overall system by addressing the problem at the formulation level rather than requiring complex administrative devices.
Data Source
AI summary
The present disclosure provides compositions comprising an antisense oligonucleotide and one or more excipients that modulates viscosity, turbidity or both viscosity and turbidity. In certain embodiments, compositions comprising an antisense oligonucleotide and one or more excipients having low viscosity are provided. In certain embodiments, compositions comprising an antisense oligonucleotide and one or more excipients having low turbidity are provided. In certain embodiments, pharmaceutical compositions comprising an antisense oligonucleotide and one or more excipients having low viscosity and turbidity are provided.