Naproxen Sodium Parenteral Formulation Using SBECD Inclusion Complex
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Solution Overview
Problem
Existing parenteral formulations of naproxen sodium face challenges with stability, hemolytic potential, and high excipient loads, which affect their suitability for rapid pain relief and long-term storage.
Innovation Solution
A stable liquid parenteral formulation of naproxen sodium is developed, comprising cyclodextrin, specifically sulfobutylether-β-cyclodextrin (SBECD), and an aqueous solvent, with a naproxen:cyclodextrin ratio ranging from 0.5:1 to 11:1, and optionally including pH modifying agents and chelating agents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If naproxen sodium is formulated as a parenteral solution for rapid pain relief, then the onset of action is faster, but the formulation stability deteriorates due to sensitivity to light, heat, acid, alkali and oxidations
Solution Approach 1:
The patent introduces cyclodextrin as an intermediary substance that forms an inclusion complex with naproxen sodium. This complexation protects the drug from degradation by light, heat, acid, alkali and oxidations while maintaining solubility in aqueous solutions, thereby achieving both rapid onset of action and improved formulation stability
Solution Approach 2:
The patent creates a composite formulation by combining naproxen sodium with cyclodextrin to form an inclusion complex. This composite structure provides both the rapid onset of action required for parenteral administration and the stability needed for long-term storage, resolving the contradiction between speed and stability
2Stability of the object's composition
If conventional stabilizing agents (polyhydric alcohols, sulphydryl compounds) are added to naproxen parenteral formulations, then stability is improved, but the excipient load increases causing hyper osmolality, hemolysis, and other adverse effects
Solution Approach 1:
The patent extracts or removes the need for conventional stabilizing agents (polyhydric alcohols, sulphydryl compounds) by using cyclodextrin inclusion complexation instead. This approach provides stability without the harmful effects of high excipient loads, eliminating hyper osmolality and hemolysis while maintaining formulation stability
Solution Approach 2:
The patent changes the stabilization mechanism from chemical additives (stabilizing agents) to physical complexation (cyclodextrin inclusion). This parameter change in the stabilization approach provides the same protective effect without introducing harmful excipients, thereby reducing hemolysis and hyper osmolality
3Stability of the object's composition
If lyophilized nanoparticulate formulations are used, then stability is improved, but the manufacturing complexity and processing time increase due to specialized equipment requirements
Solution Approach 1:
The patent uses a simple aqueous solution formulation with cyclodextrin that can be prepared and stored without complex lyophilization equipment. This approach replaces expensive, specialized manufacturing processes with a simpler, more accessible method while maintaining stability, effectively using a 'cheap' solution instead of 'expensive' equipment-intensive processes
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 formulation achieves >95% drug stability throughout its shelf life, reduces hemolytic factors, and minimizes excipient overload, making it suitable for parenteral administration with improved safety and efficacy.
Implementation Method 1
The present invention provides a stable liquid parenteral formulation of naproxen sodium comprising cyclodextrin, specifically sulfobutylether-β-cyclodextrin (SBECD), and an aqueous solvent
Data Source
AI summary
The present invention relates to a stable, parenteral formulations of naproxen sodium. The formulation further relates to liquid formulations comprising naproxen sodium, cyclodextrin and optionally other pharmaceutically acceptable excipients selected from pH modifying agents, chelating agents and tonicity agents. Also relates to the process of preparing the same. These formulations are stable when stored at recommended storage conditions and can be manufactured using simple manufacturing procedure. These compositions can be used to treat pain, particularly when quicker onset of action is desired. Further the present invention also relates to the parenteral formulations of naproxen in combination with additional active ingredients.