Isoxazoline Injectable Formulations with Poloxamer Co-Solvent

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Solution Overview

Problem

Current extended release injectable formulations for isoxazoline compounds face challenges in achieving desired release properties due to the hydrophobic nature of fluorinated compounds, leading to delayed hydration and degradation of polymers, and there is a need for improved duration of efficacy and bioavailability against ectoparasites and endoparasites with reduced injection site irritation.

Innovation Solution

Development of extended release injectable formulations comprising an antiparasitic effective amount of isoxazoline active agents, a pharmaceutically acceptable biodegradable polymer, and a solvent, such as poloxamers or liquid polyethylene glycols, which provide desirable bioavailability, long duration of activity, and reduced irritation at the injection site.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If fluorinated isoxazoline compounds are used in extended release formulations, then antiparasitic efficacy is improved, but polymer hydration and degradation are delayed due to hydrophobicity

Engineering Contradiction:

Improveantiparasitic efficacyVSAvoidpolymer degradation time

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent introduces a co-solvent system comprising poloxamer and polyethylene glycol as intermediary substances that mediate between the hydrophobic fluorinated isoxazoline compound and the hydrophilic polymer matrix. This co-solvent system enhances polymer hydration and accelerates degradation without compromising the antiparasitic efficacy of the active compound.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent modifies the physical-chemical parameters of the formulation by adjusting the ratio and concentration of co-solvents (poloxamer and polyethylene glycol) to optimize both drug release kinetics and polymer degradation rate, thereby resolving the contradiction between maintaining efficacy and enabling timely release.

Inventive Principle:

Principle #35Parameter changes

2Duration of action of moving object

If extended release formulations are used to prolong duration of activity, then dosing frequency is reduced, but injection site irritation increases

Engineering Contradiction:

Improveduration of activityVSAvoidinjection site irritation

Core Design Contradiction:

Duration of action of moving objectVSObject-affected harmful factors

Solution Approach 1:

The co-solvent system acts as a protective intermediary that reduces direct contact between the hydrophobic active compound and injection site tissues, thereby minimizing irritation while maintaining the extended release profile and prolonged duration of activity.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent optimizes the formulation parameters including co-solvent concentration and ratio to achieve a balance between prolonging duration of activity and minimizing injection site irritation through controlled release kinetics.

Inventive Principle:

Principle #35Parameter changes

3Duration of action of moving object

If polymer concentration is increased to extend release duration, then release rate is reduced, but bioavailability may be compromised

Engineering Contradiction:

Improverelease durationVSAvoidbioavailability

Core Design Contradiction:

Duration of action of moving objectVSReliability

Solution Approach 1:

The co-solvent system serves as a mediator that facilitates drug-polymer interaction and maintains drug solubility within the polymer matrix, ensuring adequate bioavailability even at higher polymer concentrations that extend release duration.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent adjusts multiple formulation parameters including polymer concentration, co-solvent ratio, and drug-to-polymer ratio to achieve optimal balance between extended release duration and maintained bioavailability through controlled release kinetics.

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 formulations exhibit superior broad-spectrum efficacy against ectoparasites like fleas and ticks for an extended duration, with fast onset and favorable safety profiles, while minimizing irritation and ensuring effective parasite control in animals.

Implementation Method 1

a pharmaceutically acceptable biodegradable polymer

Methodology Applied

Scientific EffectHydrolysis: Hydrolysis

Implementation Method 2

delayed hydration and degradation of polymers

Methodology Applied

Scientific EffectHydration: Mineral Hydration

Data Source

PatentUS20210299104A1Extended release injectable formulations comprising an isoxazoline active agent, methods and uses thereof

Publication Date: 2021.09.30 BOEHRINGER INGELHEIM ANIMAL HEALTH USA INC

AI summary

This invention relates to extended release injectable formulations for combating parasites in animals, comprising at least one isoxazoline active agent, a pharmaceutically acceptable polymer, and a solvent. This invention also provides for improved methods for eradicating, controlling, and preventing parasite infections and infestations in an animal comprising administering the extended release injectable formulations of the invention to the animal in need thereof.