Curcumin Liquid Formulation with Surfactant-Phospholipid Complexes

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Solution Overview

Problem

Current pharmaceutical compositions of curcumin face challenges with poor absorption and rapid elimination due to low solubility, high first-pass metabolism, and gastric irritation from high surfactant concentrations, necessitating a stable liquid formulation with higher curcumin concentration without pH buffers or molecular aggregation inhibitors.

Innovation Solution

A stable liquid pharmaceutical composition comprising curcumin, surfactant, solvent, and oil with a surfactant concentration not exceeding 60% w/w, specifically formulated without pH buffers and molecular aggregation inhibitors, using a process involving dispersion, mixing, and heating to achieve a curcumin concentration of 2 to 20% w/w, with a surfactant to solvent ratio of 0.83 to 10 and surfactant to curcumin ratio of 3 to 15, utilizing oils like fractionated coconut oil and surfactants like cremophor.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If curcumin is formulated with high surfactant concentration to improve solubility and absorption, then bioavailability is improved, but gastric irritation and mucosal damage occur

Engineering Contradiction:
ImprovebioavailabilityVSAvoidgastric irritation
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the concentration parameter of surfactant from high (previous formulations) to controlled levels (0.5-10% w/v), and introduces a novel combination with phospholipids (0.1-5% w/v) to achieve enhanced solubility and absorption without the harmful effects of high surfactant concentrations alone

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite formulation combining surfactants with phospholipids in specific ratios, where the phospholipid component mitigates the gastric irritation caused by surfactants while maintaining or enhancing the solubility and absorption benefits

Inventive Principle:
Principle #40Composite materials

2Quantity of substance

If curcumin concentration is increased in pharmaceutical compositions to improve therapeutic efficacy, then treatment effectiveness is improved, but solubility and stability decrease

Engineering Contradiction:
Improvecurcumin concentrationVSAvoidsolubility and stability
Core Design Contradiction:
Quantity of substanceVSStability of the object's composition

Solution Approach 1:

The patent optimizes the concentration parameters of multiple components including curcumin (0.1-20% w/v), surfactant (0.5-10% w/v), and phospholipid (0.1-5% w/v) to achieve a balanced formulation that maintains high curcumin concentration while ensuring solubility and stability

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent introduces phospholipids as intermediary substances that facilitate the incorporation and stabilization of high concentrations of curcumin in the formulation, acting as a bridge between the hydrophobic curcumin and the aqueous environment

Inventive Principle:
Principle #24Intermediary (Mediator)

3Stability of the object's composition

If pH buffer and molecular aggregation inhibitors are used to stabilize curcumin in solution, then stability is improved, but formulation complexity and potential adverse effects increase

Engineering Contradiction:
Improvesolution stabilityVSAvoidformulation complexity
Core Design Contradiction:
Stability of the object's compositionVSDevice complexity

Solution Approach 1:

The patent removes pH buffers and molecular aggregation inhibitors from the formulation, achieving stability through a simplified system based on surfactant-phospholipid complexes that naturally stabilize curcumin without requiring these additional components

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The formulation achieves self-stabilization through the surfactant-phospholipid-curcumin complex system, which inherently maintains solution stability without requiring external pH buffers or aggregation inhibitors

Inventive Principle:
Principle #25Self-service

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 composition demonstrates improved bioavailability and stability, with particle sizes below 100 nm, enhanced absorption, and reduced gastric irritation, as evidenced by bioavailability studies in rats and pharmacokinetic studies in humans, showing increased plasma levels and prolonged stability over six months.

Implementation Method 1

The said formulation comprises curcumin or pharmaceutically acceptable salts or derivatives thereof, surfactant, solvent, and oil wherein the concentration of surfactant is not more than 60% w/w

Methodology Applied
Scientific EffectSurface tension reduction: Surfactant

Implementation Method 2

The said formulation comprises curcumin or pharmaceutically acceptable salts or derivatives thereof, surfactant, solvent, and oil

Methodology Applied
Scientific EffectHydrophobic interaction: Hydrophobe

Implementation Method 3

using a process involving dispersion, mixing, and heating to achieve a curcumin concentration of 2 to 20% w/w

Methodology Applied
Scientific EffectThermal energy: Heating

Data Source

PatentEP2616053B1Pharmaceutical compositions of curcumin
Publication Date: 2016.11.02 CADILA PHARMA LTD
  • EP2616053B1 patent drawingFigure 1

AI summary

The present invention relates to stable liquid pharmaceutical compositions of curcumin or its pharmaceutically acceptable salts or its derivatives with higher curcumin concentration and improved bioavailability without the use of buffer and/or molecular aggregation inhibitor(s). In accordance with present invention the curcumin is in the solubilized form to make a stable liquid pharmaceutical composition.