Fipronil Formulation Stability via Glycol Ether Solvents

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Solution Overview

Problem

Existing veterinary compositions containing N-phenylpyrazole derivatives, such as fipronil, face challenges in formulation stability due to crystallization issues and require complex excipient combinations, which can lead to inefficiencies and increased costs.

Innovation Solution

A stable liquid pharmaceutical formulation using fipronil, a glycol ether as the main carrier, and mono alkyl ester co-solvents like ethyl acetate and ethyl lactate, along with a crystallization inhibitor, to create a simple and cost-effective topical treatment for fleas and ticks.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If N-phenylpyrazole derivatives are formulated with common excipients for topical pesticide treatments, then the formulation can be applied topically, but the formulation has significant potential for crystallisation and stability issues

Engineering Contradiction:
Improvetopical application capabilityVSAvoidformulation stability
Core Design Contradiction:
Ease of operationVSStability of the object's composition

Solution Approach 1:

The patent changes the physical-chemical parameters of the formulation by using a specific solvent system (glycol ethers with dielectric constants of 10-35) and co-solvents with specific boiling points and dielectric constants. This parameter optimization prevents crystallization of fipronil while maintaining topical applicability, resolving the contradiction between ease of operation and formulation stability.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent employs a composite formulation system combining glycol ether solvents, co-solvents, and crystallization inhibitors in specific ratios. This composite approach creates a synergistic effect that maintains fipronil solubility and prevents crystallization, thereby achieving both topical application capability and formulation stability.

Inventive Principle:
Principle #40Composite materials

2Stability of the object's composition

If alternative formulation systems with multiple crystallisation inhibitors and solvent/co-solvents are used, then crystallisation is prevented, but the formulation complexity and manufacturing cost increase

Engineering Contradiction:
Improvecrystallisation preventionVSAvoidformulation complexity
Core Design Contradiction:
Stability of the object's compositionVSDevice complexity

Solution Approach 1:

The patent extracts and focuses on the most critical components for preventing crystallization, using a simplified system of glycol ether solvents and specific co-solvents rather than combining multiple crystallization inhibitors. This extraction approach maintains crystallization prevention while reducing formulation complexity and manufacturing cost.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent optimizes the dielectric constant range of the solvent (10-35) and co-solvent (10-40) to achieve effective crystallization prevention with minimal components. By carefully selecting parameters within specific ranges, the formulation achieves stability without requiring complex multi-component systems.

Inventive Principle:
Principle #35Parameter changes

3Stability of the object's composition

If alternative formulation systems with multiple crystallisation inhibitors and solvent/co-solvents are used, then crystallisation is prevented, but the manufacturing cost increases

Engineering Contradiction:
Improvecrystallisation preventionVSAvoidmanufacturing cost
Core Design Contradiction:
Stability of the object's compositionVSEase of manufacture

Solution Approach 1:

The patent uses relatively inexpensive glycol ether solvents and common co-solvents that are readily available and cost-effective, replacing more expensive specialized crystallization inhibitors. This approach prevents crystallization while maintaining cost-effectiveness and ease of manufacture.

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent identifies specific parameter ranges for solvents and co-solvents that optimize both crystallization prevention and cost-effectiveness. By formulation within these parameter ranges, the patent achieves stable formulations using cost-effective materials, reducing manufacturing costs while maintaining efficacy.

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 formulation provides a stable, easy-to-manufacture, and cost-effective solution for preventing and treating flea and tick infestations in pets, maintaining fipronil efficacy and stability over time.

Implementation Method 1

A stable liquid pharmaceutical formulation using fipronil, a glycol ether as the main carrier, and mono alkyl ester co-solvents like ethyl acetate and ethyl lactate

Methodology Applied
Scientific EffectSolvation: Solvation

Implementation Method 2

along with a crystallization inhibitor, to create a simple and cost-effective topical treatment for fleas and ticks

Methodology Applied
Scientific EffectCrystallization inhibition: Crystallisation

Data Source

PatentUS8653128B1Veterinary composition and method
Publication Date: 2014.02.18 BELCHER PHARMACEUTICALS LLC

AI summary

A stable liquid pharmaceutical formulation containing an N-phenylpyrazole derivative, a crystallization inhibitor/viscolizer and a solvent/co-solvent system comprised of a glycol ether solvent and at least one mono alkyl ester co-solvent; and the use of such a formulation for the prevention and/or treatment of infestations with fleas and ticks.