Salicylanilide Parasiticidal Composition with Polymeric Bioavailability Enhancement

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Solution Overview

Problem

Existing formulations of ivermectin and closantel combination products for veterinary use fail to achieve satisfactory bioavailability of closantel when administered via injection, with blood plasma levels below expected levels despite increased dosing, due to differences in optimal pH requirements and solubility issues.

Innovation Solution

Incorporating a significant amount of polyvinylpyrrolidone (PVP) or polyoxypropylene/polyoxyethylene block copolymer in the solvent system, particularly with glycerol formal, propylene glycol, or polyethylene glycol, to enhance the bioavailability of closantel, achieving effective blood plasma levels greater than 20 ppm.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional solvent systems are used for injectable formulations, then the formulation can be prepared with standard vehicles, but the bioavailability of closantel is insufficient and blood plasma levels remain below expected levels

Engineering Contradiction:
Improvebioavailability of closantelVSAvoidblood plasma levels of closantel
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

The patent changes the chemical parameters of the solvent system by introducing polyvinylpyrrolidone (PVP) as a polymeric species that interacts with closantel to enhance its bioavailability. This parameter change in the formulation composition enables achieving blood plasma levels greater than 20 ppm, resolving the contradiction between reliability of bioavailability and quantity of substance delivered.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

PVP acts as an intermediary substance in the formulation that mediates between the closantel and the biological system. The polymeric species facilitates the absorption and distribution of closantel, thereby improving bioavailability and achieving therapeutic blood plasma levels without requiring increased dosing.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If dosing is increased to achieve satisfactory bioavailability, then blood plasma levels improve, but the formulation complexity and potential toxicity increase

Engineering Contradiction:
Improvebioavailability of closantelVSAvoidtoxicity and adverse reactions
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

PVP serves as a beneficial intermediary that enhances closantel bioavailability through formulation mechanisms rather than requiring increased dosing. This approach achieves satisfactory blood plasma levels while avoiding the toxicity and adverse reactions associated with higher doses, thus resolving the contradiction between bioavailability improvement and harmful effects.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Adaptability or versatility

If a combination product is formulated to achieve broad spectrum efficacy, then the treatment effectiveness improves, but the formulation complexity increases

Engineering Contradiction:
Improvebroad spectrum of parasitesVSAvoidformulation complexity
Core Design Contradiction:
Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent merges avermectin/milbemycin and closantel into a single injectable formulation, combining the broad spectrum efficacy of avermectin with the specific activity of closantel against flukes and other parasites. This merging achieves comprehensive parasite coverage while managing formulation complexity through the use of PVP as a unifying solvent system that accommodates both active ingredients.

Inventive Principle:
Principle #5Merging (Combining)

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 PVP in the formulation significantly increases the bioavailability of closantel, allowing for effective treatment with controllable efficacy and compliance with withdrawal periods for human consumption, while maintaining the effectiveness of ivermectin against a broad range of parasites.

Implementation Method 1

the inclusion of a significant amount of a polymeric moiety, especially polyvinylpyrrolidone (PVP) has a dramatic effect on the bioavailability of salicylanilides such as closantel in parasiticidal formulations

Methodology Applied
Scientific EffectAbsorption: Absorption (physical)

Implementation Method 2

Injectable formulations are typically prepared using aqueous or non-aqueous ('solvent') vehicles

Methodology Applied
Scientific EffectDissolution: Solvation

Data Source

PatentUS9289380B2Long acting parasiticidal composition containing a salicylanilide compound, a polymeric species and at least one other anti-parasitic compound
Publication Date: 2016.03.22 NORBROOK LABORATORIES LIMITED

AI summary

A composition prepared for treating animals suffering from parasites which parasites are known to be susceptible to at least one of the avermectins, milbemycins or salicylanilides, comprises for example ivermectin in an amount of from 0.1 to 10%(w/v), a solvent selected from the group consisting of glycerol formal, propylene glycol, polyethylene glycol and combinations thereof, and a salicylanilide such as closantel in a required dosage amount for the animal to be treated, typically about 2.5 mg/kg live weight of the animal to be treated, a polymeric species selected from the group consisting of polyvinylpyrrolidone and polyoxypropylene/polyoxyethylene block copolymers, the said polymeric species improving the bioavailability of closantel to the extend that blood plasma levels of the said compound greater than about 20 ppm over period of treatment are achievable.