Self-Emulsifying Anhydrous Gel for Poorly Water-Soluble Drug Delivery

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Solution Overview

Problem

Many drugs, including tetrahydrocannabinol (THC) and cannabidiol (CBD), are poorly soluble in aqueous media, leading to poor bioavailability and variable dissolution rates, which hampers their therapeutic efficacy due to their extreme water insolubility.

Innovation Solution

A self-emulsifying anhydrous gel (SEAG) is developed, comprising a mixture of propylene glycol, glycerin, ethoxy diglycol, hydroxypropylcellulose, butylated hydroxytoluene, caprylic acid triglyceride, and edetate disodium, which forms an intradermal depot and uses a solubilizer/emulsifier like Kolliphor HS15 or lecithin to enhance solubility and skin retention of cannabinoids.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If drugs are administered in conventional forms, then they are easy to manufacture and apply, but their bioavailability is poor due to water insolubility

Engineering Contradiction:
ImprovebioavailabilityVSAvoidformulation complexity
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent employs a composite delivery system combining multiple components: a self-emulsifying drug delivery system (SEDDS) with oil phase, surfactant, and co-surfactant, encapsulated within a hydrogel matrix. This composite structure enables poor water-soluble drugs to achieve enhanced bioavailability through emulsification while the hydrogel provides controlled release and skin retention, resolving the contradiction between bioavailability improvement and formulation complexity.

Inventive Principle:
Principle #40Composite materials

Solution Approach 2:

The patent utilizes parameter changes by adjusting the composition ratios of the SEDDS components (oil phase, surfactant, co-surfactant) and the hydrogel matrix to optimize drug solubility and release characteristics. By modifying these physical-chemical parameters, the system achieves improved bioavailability without requiring complex manufacturing processes, as the formulation self-emulsifies upon contact with aqueous media.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If surfactants are used to improve solubility, then bioavailability increases, but skin irritation and stability issues arise

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

Solution Approach 1:

The patent introduces a co-surfactant as an intermediary substance that works synergistically with the primary surfactant to reduce skin irritation while maintaining solubility enhancement. The co-surfactant modulates the surfactant's activity, allowing effective drug solubilization without the harmful effects of high surfactant concentrations, thus resolving the contradiction between solubility improvement and skin irritation prevention.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent applies local quality by using the hydrogel matrix to locally control surfactant release and concentration at the application site. The hydrogel provides a controlled environment that maintains optimal surfactant levels for solubility enhancement while preventing excessive surfactant accumulation that would cause skin irritation, effectively separating the solubility function from the irritation problem.

Inventive Principle:
Principle #3Local quality

3Speed

If rapid absorption is achieved, then immediate therapeutic effect occurs, but duration of action is reduced

Engineering Contradiction:
Improveabsorption rateVSAvoidduration of action
Core Design Contradiction:
SpeedVSDuration of action of moving object

Solution Approach 1:

The patent segments the drug delivery process into two distinct phases: an initial rapid absorption phase where the self-emulsifying system quickly releases drug for immediate therapeutic effect, followed by a sustained release phase where the hydrogel matrix gradually releases remaining drug. This segmentation resolves the contradiction by providing both rapid onset and prolonged duration of action through different release mechanisms operating at different time scales.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The patent employs dynamic release characteristics where the formulation transitions from rapid emulsification and absorption to gradual hydrogel degradation and drug release. The system's release rate is not static but evolves over time, initially providing fast absorption for immediate effect then transitioning to slow release for extended duration, dynamically adapting to meet both contradictory requirements.

Inventive Principle:
Principle #15Dynamics

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 SEAG increases the bioavailability and duration of action for poorly water-soluble drugs by forming a solubilized dispersion that retains drugs in the skin, allowing for effective topical and oral delivery, including cannabis and minor cannabinoids, with adjustable ratios of ethoxy diglycol to propylene glycol controlling the depth of skin penetration.

Implementation Method 1

SEAG is a hydrophilic solvent-based, anhydrous drug delivery system, utilizing ethoxy diglycol, which presents the cannabinoids in a solubilized state in a solubilized dispersion. It is a gel containing solid or liquid surfactants, one or more hydrophilic solvents which have the unique ability to form fine oil-in-water emulsions when in contact with aqueous media

Methodology Applied
Scientific EffectSelf-emulsification: Emulsion

Implementation Method 2

A self-emulsifying, anhydrous gel (SEAG), which forms an intradermal depot of the active ingredients after being absorbed, is provided which has use as carrier for topical delivery of poorly water-soluble medicaments

Methodology Applied
Scientific EffectAbsorption: Absorption (physical)

Implementation Method 3

The invention also comprises a combination of the carrier, with an oral-based, bioadhesive paste, which allows the gel to adhere mucosally when used orally for use, for example, in conjuction with a stent or other dental appliance. In another embodiment of the invention, the SEAG further includes a solubilizer/emulsifier, such as Kollipher HS15 or lecithin

Methodology Applied
Scientific EffectSolubilization: Solvation

Data Source

PatentUS11660284B2Self-emulsifying anhydrous intradermal depot gel
Publication Date: 2023.05.30 MEDPHARM HOLDINGS LLC

AI summary

The present invention relates to compositions and methods to solubilize poorly water-soluble medicaments using a self-emulsifying, anhydrous gel (SEAG), which then forms an intradermal depot when absorbed. The gel preferably comprises a mixture of propylene glycol, glycerin, ethoxy diglycol, hydroxypropylcellulose, butylated hydroxytoluene, caprylic acid triglyceride and edetate disodium, and may further include an oral-based, bioadhesive paste, which allows the gel to adhere mucosally. The SEAG may further contain a solubilizer such as Kolliphor HS15.