Paracetamol Injection Solvent System for Low Viscosity

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Solution Overview

Problem

Current parenteral paracetamol formulations fail to deliver a therapeutic dose of 500 mg in a single dose via intramuscular administration without causing pain and are not suitable for concurrent use with IV infusions, requiring additional infrastructure and storage, and existing high-concentration solutions are either too viscous or unsuitable for intramuscular use.

Innovation Solution

Development of high-concentration parenteral compositions of paracetamol (166-250 mg/ml) using solvent systems like glycofurol, ethanol, and water, which are less viscous (<28 cps) and suitable for both intramuscular and intravenous administration, allowing for a full therapeutic dose in 2-3 ml volumes, and compatibility with various IV fluids.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Volume of moving object

If high concentration paracetamol solutions (150 mg/ml or higher) are prepared to deliver therapeutic dose in small volume, then the volume of injection is reduced, but the viscosity increases causing pain on intramuscular administration

Engineering Contradiction:
Improvevolume of injectionVSAvoidpain on administration
Core Design Contradiction:
Volume of moving objectVSObject-affected harmful factors

Solution Approach 1:

The patent changes the physical-chemical parameters of the solvent system by using glycofurol as the primary solvent instead of conventional water or alcohol-based solutions. This parameter change enables the formulation of high-concentration paracetamol solutions (166-250 mg/ml) that maintain low viscosity (<28 cps) suitable for intramuscular administration, thereby resolving the contradiction between reduced volume and acceptable viscosity

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite solvent system combining glycofurol with specific ratios of water and other compatible solvents (e.g., propylene glycol, polyethylene glycol). This composite approach allows achieving both high paracetamol concentration (166-250 mg/ml) and low viscosity by leveraging the synergistic properties of the solvent mixture, enabling therapeutic dose delivery in small volumes without causing administration pain

Inventive Principle:
Principle #40Composite materials

2Speed

If concentrated parenteral formulations are developed to provide rapid onset of action, then the pharmacologic action is accelerated, but the formulations are unsuitable for intramuscular route due to high viscosity

Engineering Contradiction:
Improveonset of pharmacologic actionVSAvoidsuitability for intramuscular administration
Core Design Contradiction:
SpeedVSEase of operation

Solution Approach 1:

The patent employs parameter changes by formulating concentrated paracetamol solutions (166-250 mg/ml) in glycofurol-based solvents that maintain low viscosity (<28 cps). This parameter optimization allows the solution to be administered intramuscularly while still providing rapid onset of pharmacologic action, thus resolving the contradiction between speed of action and ease of intramuscular administration

Inventive Principle:
Principle #35Parameter changes

3Adaptability or versatility

If aqueous solutions of paracetamol are prepared at 10 mg/ml for intravenous infusion, then the solution is compatible with IV administration, but additional infrastructure and storage space are required

Engineering Contradiction:
Improvecompatibility with IV infusionVSAvoidinfrastructure and storage requirements
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent changes the concentration parameter from conventional 10 mg/ml to high concentration (166-250 mg/ml) while maintaining IV compatibility through the glycofurol-based solvent system. This parameter change allows the same vial to serve both IV infusion and intramuscular administration, reducing the need for separate infrastructure and storage arrangements

Inventive Principle:
Principle #35Parameter changes

4Quantity of substance

If multiple doses are administered to achieve therapeutic dosage from high concentration solutions, then the concentration can be maintained, but the administration process becomes more complex

Engineering Contradiction:
Improveconcentration of paracetamolVSAvoidadministration process
Core Design Contradiction:
Quantity of substanceVSEase of operation

Solution Approach 1:

The patent optimizes the concentration parameter to achieve exactly 500 mg therapeutic dose in a single 2-3 ml injection (166-250 mg/ml), eliminating the need for multiple doses. This parameter optimization simplifies the administration process to a single injection while maintaining high concentration, thus resolving the contradiction between concentration maintenance and administration simplicity

Inventive Principle:
Principle #35Parameter changes

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 compositions enable efficient delivery of a full therapeutic dose of paracetamol in a smaller volume with reduced viscosity, making them suitable for both intramuscular and intravenous routes and compatible with multiple IV fluids, enhancing administration convenience and reducing storage and infrastructure needs.

Implementation Method 1

high-concentration parenteral compositions of paracetamol (166-250 mg/ml) using solvent systems like glycofurol, ethanol, and water

Methodology Applied
Scientific EffectSolubility: Solvation

Data Source

PatentEP2588097B1Pharmaceutical compositions comprising paracetamol and process for preparing the same
Publication Date: 2021.02.24 TROIKAA PHARMACEUTICALS LTD

AI summary

Disclosed herein are injectable compositions containing high concentration of paracetamol or its pharmaceutically acceptable salts wherein the concentration of paracetamol or its pharmaceutically acceptable salt is &gt;150mg/ml in a judiciously tailored solvent system comprising glycofurol, ethanol, water or a solvent system comprising glycofurol, ethanol, polyethylene glycol, water. The viscosity of the said injectables is &lt;28 cps. Further disclosed is the process for preparing the said injectables. The injectables can be administered by intramuscular route, intravenous route or as intravenous infusion after diluting in one of the routinely used intravenous fluids, infusion solutions of antibacterial, antifungal and amoebicidal drugs and along with anxiolytics (Midazolam injection ) or narcotic analgesics (Fentanyl Citrate injection etc) as they remain stable, clear and transparent atleast for 6 hours after dilution.