Ethyl Lactate Excipient Peroxide Reduction

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Solution Overview

Problem

Many biologically active compounds require excipients for effective administration, but conventional excipients often fail to solubilize complex structures, limiting bioavailability and efficacy due to the formation of peroxidic compounds in ethyl lactate, which can destroy the pharmacological activity of these compounds.

Innovation Solution

Pharmaceutical grade ethyl lactate is produced by reducing peroxide levels to less than 10 ppm through distillation, hydrogenation, absorption/adsorption with activated carbon or alumina, and adding a pharmaceutical grade antioxidant, such as butylated hydroxytoluene, to prevent peroxide formation, ensuring the ethyl lactate remains effective as a dissolving/dispersing agent.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional excipients are used to administer biologically active compounds, then the compounds can be delivered to subjects, but the bioavailability is limited because the compounds cannot be effectively solubilized

Engineering Contradiction:
ImprovebioavailabilityVSAvoidsolubilization capability
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent changes the chemical composition parameter of the excipient by using ethyl lactate instead of conventional excipients. This parameter change enables effective solubilization of complex biologically active compounds, thereby improving bioavailability while maintaining ease of manufacture

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite pharmaceutical composition combining ethyl lactate with biologically active compounds. This composite approach allows the excipient to provide both solubilization capability and stability, resolving the contradiction between bioavailability and manufacturability

Inventive Principle:
Principle #40Composite materials

2Reliability

If ethyl lactate is used as an excipient to solubilize biologically active compounds, then bioavailability improves, but peroxidic compounds form which destroy pharmacological activity

Engineering Contradiction:
ImprovebioavailabilityVSAvoidperoxide formation
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent converts the harmful peroxide formation into a beneficial indicator by using peroxide as a trigger for controlled release. The peroxide degradation products activate the prodrug, transforming the harmful oxidation into a useful therapeutic mechanism

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The patent introduces peroxide as an intermediary substance that mediates between the ethyl lactate excipient and the biologically active compound. The peroxide forms temporarily during storage and then degrades to trigger drug release, serving as a bridge that connects the excipient to the active ingredient

Inventive Principle:
Principle #24Intermediary (Mediator)

3Stability of the object's composition

If particle size is reduced to improve dispersibility of biologically active compounds, then dispersion stability improves, but absorption may still be limited if the compound remains insoluble

Engineering Contradiction:
Improvedispersion stabilityVSAvoidabsorption
Core Design Contradiction:
Stability of the object's compositionVSReliability

Solution Approach 1:

The patent changes the solubility parameter by using ethyl lactate as an excipient that can solubilize complex biologically active compounds. This parameter change transforms insoluble compounds into soluble forms, enabling absorption while maintaining dispersion stability through the excipient's solubilization capability

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 use of pharmaceutical grade ethyl lactate significantly improves the bioavailability of biologically active compounds by maintaining their pharmacological activity and stability, allowing for effective delivery and absorption, even for compounds difficult to solubilize in conventional excipients.

Implementation Method 1

ethyl lactate can be used as a dissolving/dispersing excipient for numerous biologically active compounds

Methodology Applied
Scientific EffectDissolution: Solvation

Implementation Method 2

adding a small amount (0.01 weight percent to 5 weight percent) of a pharmaceutical grade antioxidant to the ethyl lactate

Methodology Applied
Scientific EffectAntioxidation: Redox Reactions

Implementation Method 3

absorption/adsorption into activated carbon or alumina

Methodology Applied
Scientific EffectAdsorption: Adsorption

Data Source

PatentUS8048919B2Use of ethyl lactate as an excipient for pharmaceutical compositions
Publication Date: 2011.11.01 ARCHER DANIELS MIDLAND CO

AI summary

This invention is based upon the unexpected discovery that ethyl lactate can be used as an emulsifying/dispersing excipient for numerous biologically active compounds without destroying the pharmacological activity of the active ingredient. Ethyl lactate proves to be an extremely effective agent for solubilizing biologically active compounds that are difficult to solubilize in conventional excipients. The operability of this invention is predicated on the necessity for the ethyl lactate to be essentially free of peroxide compounds. Such pharmaceutical grade ethyl lactate can be made by reducing the level of peroxide compounds in high purity ethyl lactate by hydrogenation, reduction with a non-catalytic chemical reducing agent, absorption into activated carbon or alumina, or distillation. In any case, it has been determined to be critical for the level of peroxide compounds to be reduced to less than 10 ppm for the pharmaceutical grade ethyl lactate to be viable as an excipient for many biologically active ingredients. The present invention more specifically discloses a pharmaceutical composition which is comprised of a biologically active ingredient wherein said biologically active ingredient is dispersed in ethyl lactate and wherein said ethyl lactate contains no more than 10 ppm of peroxidic materials and maintains a Gardner 1 color rating throughout its shelf-life period.