Sustained-Release Injectable Formulation Using Reverse Thermal Gelation

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Solution Overview

Problem

Sustained release formulations in veterinary medicine face challenges with solubility limitations, requiring multiple administrations and complicating injection site safety and drug protocol compliance due to the limited amount of biologically active ingredient that can be dissolved in a solution for injection.

Innovation Solution

A sustained release formulation using polymers like poloxamers that form gels, allowing a higher concentration of biologically active agents in an undissolved form, enabling controlled release through gradual dissolution and reducing the need for multiple dosing.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of moving object

If the amount of biologically active agent is increased to achieve prolonged release, then the duration of action is improved, but the solubility limitation requires use of solution volume that substantially exceeds acceptable injection volume

Engineering Contradiction:

Improveduration of efficacyVSAvoidinjection volume

Core Design Contradiction:

Duration of action of moving objectVSVolume of moving object

Solution Approach 1:

The patent changes the physical state parameter of the biologically active agent from dissolved (solution) to undissolved (suspension) form. This allows incorporating much higher amounts of active agent (e.g., 10-50 times more) in the same injection volume, thereby extending the duration of action without exceeding acceptable injection volume limits.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite formulation combining undissolved biologically active agent particles with a gel matrix. The gel matrix (formed by polymers like poloxamers) provides structural support and controlled release properties, while the undissolved active agent particles provide high drug loading capacity. This composite structure enables both prolonged release and acceptable injection volume.

Inventive Principle:

Principle #40Composite materials

2Volume of moving object

If multiple administrations are required to overcome solubility limitations, then the acceptable injection volume is maintained, but the complexity of drug protocol compliance increases and patient safety is reduced

Engineering Contradiction:

Improveinjection volumeVSAvoidpatient safety and compliance

Core Design Contradiction:

Volume of moving objectVSReliability

Solution Approach 1:

The patent performs preliminary action by formulating all required doses of biologically active agent into a single injectable suspension before administration. This eliminates the need for multiple separate administrations, thereby improving patient compliance and reducing injection site complications while maintaining safe injection volume per administration.

Inventive Principle:

Principle #10Preliminary action

3Duration of action of moving object

If the concentration of biologically active agent is increased in solution form, then the duration of action is improved, but the solubility of the agent is exceeded

Engineering Contradiction:

Improveduration of efficacyVSAvoidsolubility

Core Design Contradiction:

Duration of action of moving objectVSStability of the object's composition

Solution Approach 1:

Instead of trying to dissolve more active agent in the solution (conventional approach), the patent inverts the approach by using undissolved active agent particles in suspension. This reversal allows achieving high concentrations (e.g., 10-50 times higher) without exceeding solubility limits, as the active agent remains in solid particulate form throughout the formulation.

Inventive Principle:

Principle #13The other way round (Inversion)

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 formulation achieves prolonged treatment with a single administration, increasing the duration of efficacy and reducing dosing frequency while maintaining acceptable injection volumes, thus improving patient safety and compliance.

Implementation Method 1

In aqueous solutions at concentrations above the critical micelle concentration (CMC) these copolymers self-assemble into micelles. The core of the micelles consists of hydrophobic PPO blocks that are separated from the aqueous exterior by a hydrated shell of PEO blocks.

Methodology Applied

Scientific EffectMicelle formation: Self-Assembly

Implementation Method 2

a polymer which exhibits reverse thermal gelation at a physiological temperature

Methodology Applied

Scientific EffectReverse thermal gelation: Gel

Data Source

PatentUS11052043B2Sustained-release injectable formulation

Publication Date: 2021.07.06 YISSUM RESEARCH DEVELOPMENT COMPANY OF THE HEBREW UNIVERSITY OF JERUSALEM LTD

AI summary

A composition which comprises a biologically active agent and a polymer that exhibits a reverse thermal gelation at a physiological temperature, in a carrier, and in which the active agent is in an undissolved form is disclosed herein. Further disclosed herein are methods utilizing the compositions for treating subjects, including non-human subjects, as well as kits for preparing and using a composition. The composition is preferably a sustained release formulation, and is particularly useful for treating animals, where single-dose treatment is desired.