Stable Ketoprofen Amitriptyline Oxymetazoline Injection Formulations
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Solution Overview
Problem
Conventional pharmaceutical irrigation fluids lack analgesic and anti-inflammatory effects, and stable liquid formulations of ketoprofen, amitriptyline, and oxymetazoline are challenging due to solubility and stability issues, particularly in aqueous solutions where these drugs are prone to chemical degradation.
Innovation Solution
The development of stable liquid pharmaceutical formulations of ketoprofen, amitriptyline, and oxymetazoline that include 1-99% polyol, 10-500 mM sodium citrate, and a pH of 4.5-7.0, with polyethylene glycol (PEG) as a preferred polyol, and the addition of sodium ethylenediamine tetraacetic acid (EDTA) to enhance stability, allowing for prolonged storage without significant degradation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional physiologic irrigation fluids are used, then the surgical site can be irrigated, but the fluids do not provide analgesic or anti-inflammatory effects
Solution Approach 1:
The patent combines multiple therapeutic agents (ketoprofen, amitriptyline, and oxymetazoline) with physiologic irrigation fluid to create a multi-functional solution that provides both irrigation and therapeutic effects (analgesic and anti-inflammatory) simultaneously, eliminating the need for separate medication administration
2Reliability
If lyophilized drug combination is reconstituted and used in dilute irrigation solution, then therapeutic benefits are achieved, but the formulation is complex and requires multiple steps
Solution Approach 1:
The patent pre-formulates the therapeutic agents in a stable concentrated liquid solution with appropriate solvents and stabilizers, allowing the solution to be stored ready-to-use and simply diluted with irrigation fluid during surgery, eliminating the need for lyophilization and reconstitution steps
3Stability of the object's composition
If stable liquid formulations of ketoprofen, amitriptyline, and oxymetazoline are developed, then solubility and shelf life are improved, but formulation stability is challenging due to chemical degradation
Solution Approach 1:
The patent uses stabilizers and appropriate pH buffers as intermediary substances that protect the therapeutic agents from chemical degradation, oxidation, and hydrolysis, maintaining formulation stability and preventing drug decomposition during storage
Solution Approach 2:
The patent optimizes formulation parameters including pH level, solvent composition, and stabilizer concentration to create a chemical environment that minimizes drug degradation and maintains long-term stability of the liquid formulation
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 formulations maintain stability for at least six months to several years at temperatures ranging from 2°C to 30°C, significantly improving the solubility and shelf life of the drugs compared to lyophilized forms, ensuring effective anti-inflammatory and analgesic action during surgical and therapeutic procedures.
Implementation Method 1
The formulations include 1-99% polyol, and 10-500 mM sodium citrate at a pH of 4.5-7.0
Implementation Method 2
10-500 mM sodium citrate at a pH of 4.5-7.0
Implementation Method 3
the addition of sodium ethylenediamine tetraacetic acid (EDTA) to enhance stability
Data Source
Figure 1A
Figure 1B
Figure 2A
AI summary
The present invention relates to stable liquid formulations of ketoprofen, amitriptyline, and oxymetazoline.