Injectable Ibuprofen Solubilization Without Phase Transitions
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Solution Overview
Problem
Existing ibuprofen formulations, particularly injectable solutions, face challenges with solubility issues due to poor water solubility, requiring the formation of salts and involving complex processes that increase costs and potential side effects, and do not maintain stability across a wide concentration range without phase transitions.
Innovation Solution
A pharmaceutical composition using an ibuprofen solubilizing agent like sodium or potassium phosphate, sodium carbonate, sodium hydroxide, or L-lysine, maintaining ibuprofen solubility from 100 mg/mL to 5 mg/mL without phase transitions, with molar ratios less than or equal to 1:1, and a pH range of 6.8 to 7.8, allowing for stable injectable solutions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If ibuprofen is formulated as a racemic mixture for simplicity, then manufacturing and formulation processes are simplified, but the biological activity is reduced since only the (S) enantiomer is actively effective
Solution Approach 1:
The patent changes the chemical parameter from racemic mixture to enantiomerically pure (S)-ibuprofen, transforming the formulation from a mixture containing both (R) and (S) enantiomers to a single active enantiomer, thereby improving biological activity while maintaining manufacturing feasibility through established chiral separation techniques
2Quantity of substance
If ibuprofen is used in high concentrations for effective dosing, then therapeutic efficacy is improved, but solubility issues arise causing phase transitions and precipitation
Solution Approach 1:
The patent introduces a solubilizing agent as an intermediary substance that forms a soluble complex with (S)-ibuprofen, enabling high concentrations (up to 100 mg/mL) to be achieved without phase transitions or precipitation, thus maintaining solution stability across a wide concentration range
Solution Approach 2:
The patent changes the physical-chemical parameters of the solution by adjusting pH to specific ranges (6.8-7.8) and incorporating solubilizing agents, which modifies the solubility characteristics of ibuprofen and prevents phase transitions at high concentrations
3Quantity of substance
If ibuprofen formulations require salt formation for solubility, then water solubility is improved, but the process complexity and potential side effects increase
Solution Approach 1:
The patent employs a solubilizing agent as an intermediary that enables direct dissolution of (S)-ibuprofen in water without requiring salt formation, thereby achieving water solubility while simplifying the formulation process and reducing the number of steps involved
Solution Approach 2:
The patent extracts and eliminates the salt formation step from the conventional formulation process, removing the need to isolate and test salts prior to producing the dosage form, thus reducing process complexity and minimizing non-active components
4Quantity of substance
If conventional ibuprofen formulations are used, then manufacturing costs are reduced, but development time increases due to required salt formation and isolation testing
Solution Approach 1:
The patent performs preliminary action by pre-establishing the use of solubilizing agents and pH adjustment protocols, which eliminates the need for subsequent salt formation and isolation testing steps, thereby reducing development time while maintaining cost-effectiveness
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 formulation that remains soluble across a wide concentration range, reducing the need for salt formation and minimizing side effects, with improved pharmacokinetics and reduced volume requirements for effective administration.
Implementation Method 1
A pharmaceutical composition using an ibuprofen solubilizing agent like sodium or potassium phosphate, sodium carbonate, sodium hydroxide, or L-lysine, maintaining ibuprofen solubility from 100 mg/mL to 5 mg/mL without phase transitions
Implementation Method 2
with a pH range of 6.8 to 7.8, allowing for stable injectable solutions
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.