Injectable Ibuprofen Solubility via pH-Adjusted Solubilizing Agent
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Solution Overview
Problem
Existing pharmaceutical compositions of ibuprofen face challenges in maintaining solubility at concentrations between 100 mg/mL and 5 mg/mL without phase transition or precipitation, particularly in injectable forms, and often require the formation of salts which increase costs and potential side effects.
Innovation Solution
A pharmaceutical composition comprising an aqueous solution of ibuprofen with a solubilizing agent such as sodium phosphate, potassium phosphate, sodium carbonate, or L-lysine, maintaining ibuprofen solubility at concentrations from 100 mg/mL to 5 mg/mL without phase transition, using a molar ratio of the solubilizing agent to ibuprofen of less than or equal to 1:1, and adjusting the pH to a range of 6.8 to 7.8 for stability and efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If ibuprofen is formulated as a racemic mixture for simplicity, then manufacturing is simplified, but biological activity is reduced since only the (S) enantiomer is active
Solution Approach 1:
The patent changes the chemical parameter from racemic mixture to enantiomerically pure (S)-ibuprofen, transforming the formulation from containing both enantiomers to containing only the active (S) enantiomer, thereby increasing biological activity while maintaining manufacturing feasibility through established chiral synthesis methods
2Quantity of substance
If ibuprofen is used in high concentrations for effective dosing, then therapeutic efficacy is improved, but solubility is compromised leading to precipitation
Solution Approach 1:
The patent introduces a solubilizing agent as an intermediary substance that forms a soluble complex with ibuprofen, enabling high concentrations (100-5 mg/mL) to be maintained in solution without precipitation. This mediator allows the therapeutic concentration to be achieved while preserving solution stability throughout the concentration range
3Ease of operation
If salts are formed to improve solubility, then injectability is improved, but cost and potential side effects increase
Solution Approach 1:
The patent employs a solubilizing agent that can be easily removed or decomposed after serving its temporary function of enabling solubility. This disposable-like approach allows the agent to be used only during formulation and administration, minimizing its presence in the final therapeutic product and reducing associated costs and side effects compared to permanent salt formations
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The solution provides a stable, clear, and colorless ibuprofen solution that remains soluble across a wide concentration range, reducing the need for salt formation and minimizing non-active components, thus enhancing safety and reducing costs, while maintaining effective dosing in smaller volumes for improved patient safety and convenience.
Implementation Method 1
A pharmaceutical composition comprising an aqueous solution of ibuprofen with a solubilizing agent such as sodium phosphate, potassium phosphate, sodium carbonate, or L-lysine, maintaining ibuprofen solubility at concentrations from 100 mg/mL to 5 mg/mL without phase transition
Implementation Method 2
adjusting the pH to a range of 6.8 to 7.8 for stability and efficacy
Data Source
AI summary
The present invention provides a pharmaceutical composition comprising an aqueous solution of an ibuprofen solubilizing agent and ibuprofen, the ibuprofen solubilizing agent being in an effective amount such that the ibuprofen in the solution remains soluble at concentrations from 100 mg/mL to 5 mg/mL without undergoing a phase transition. The invention further provides a method of treating a condition chosen from pain, inflammation, fever, and/or patent ductus arteriosis, comprising administering to a patient in need thereof an effective amount of an aqueous solution a ibuprofen solubilizing agent and ibuprofen, the ibuprofen solubilizing agent being in an effective amount such that the ibuprofen in the solution remains soluble at concentrations from 100 mg/mL to 5 mg/mL without undergoing a phase transition, as well as a method for manufacturing the composition.