Flubendazole Aqueous Suspension for Sedimentation Control
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Solution Overview
Problem
Existing pharmaceutical suspensions of flubendazole for administering to animals via water supply face stability issues, leading to sedimentation, clogging, and dosing inaccuracies due to the drug's water-insolubility and inadequate particle size distribution, which can result in resistance and underdosing.
Innovation Solution
A pharmaceutical aqueous suspension comprising flubendazole with a specific particle size distribution (D50 ≤ 0.45 micrometer and ≥ 90% ≤ 1.0 micrometer) and a non-ionic triblock copolymer surfactant with a defined PO:EO ratio, along with preservatives, is formulated to enhance physical and chemical stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If flubendazole is administered via water supply, then flexibility of administration is improved, but stability of the formulation deteriorates due to water-insolubility causing sedimentation
Solution Approach 1:
The patent changes the particle size parameter of flubendazole from conventional sizes to nanoscale (D50 ≤ 0.45 micrometer, ≥90% ≤ 1.0 micrometer). This parameter change transforms the drug's physical properties, enabling it to remain suspended in water without sedimentation while maintaining the flexibility of water-based administration.
Solution Approach 2:
The patent introduces a non-ionic triblock copolymer surfactant as an intermediary substance. This surfactant mediates between the water-insoluble flubendazole and the aqueous environment, stabilizing the nanosuspension and preventing aggregation and sedimentation, thereby enabling stable water-based administration.
2Ease of manufacture
If conventional particle size is used, then ease of manufacture is improved, but manufacturing precision deteriorates due to inadequate particle size distribution leading to dosing inaccuracies
Solution Approach 1:
The patent specifies precise particle size parameters (D50 ≤ 0.45 micrometer, ≥90% ≤ 1.0 micrometer) that balance manufacturability with dosing precision. These controlled nanoscale parameters ensure uniform suspension and accurate dosing while remaining achievable through conventional milling and homogenization processes.
Solution Approach 2:
The patent performs preliminary particle size reduction and distribution control during the formulation manufacturing process. By pre-establishing the correct nanoscale particle size distribution before administration, the system ensures both ease of manufacture and precise dosing without requiring complex post-processing.
3Stability of the object's composition
If particle size is reduced to improve stability, then physical stability is improved, but manufacturing complexity increases due to need for precise particle size control
Solution Approach 1:
The patent defines specific nanoscale particle size parameters (D50 ≤ 0.45 micrometer, ≥90% ≤ 1.0 micrometer) that achieve optimal physical stability. These parameters are sufficiently precise to ensure stability but not so restrictive as to require complex manufacturing equipment, striking a practical balance between stability and manufacturability.
Solution Approach 2:
The non-ionic triblock copolymer surfactant acts as an intermediary that simplifies the manufacturing process. It stabilizes the nanosuspension during preparation and storage, reducing the need for complex particle size control systems while maintaining the required physical stability.
4Loss of time
If sedimentation is allowed to occur, then loss of time in preparation is reduced, but reliability deteriorates due to clogging and dosing inaccuracies
Solution Approach 1:
The patent reduces particle size to nanoscale dimensions (D50 ≤ 0.45 micrometer, ≥90% ≤ 1.0 micrometer), which fundamentally changes the sedimentation behavior. Particles of this size remain colloidally suspended in water without settling, eliminating clogging risks and dosing inaccuracies while requiring no additional preparation time.
Solution Approach 2:
The non-ionic triblock copolymer surfactant serves as a intermediary that prevents sedimentation entirely. By adsorbing at the particle-water interface and providing steric stabilization, it keeps particles uniformly distributed in the water delivery system, preventing clogging and ensuring reliable dosing without requiring frequent agitation or preparation.
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 ensures long-term physical and chemical stability, preventing sedimentation and ensuring accurate dosing in medicated water, thereby maintaining effective anthelmintic efficacy without system clogging.
Implementation Method 1
a non-ionic triblock copolymer surfactant comprising a central poly(propylene oxide)-block having at least 30 propylene oxide (PO) units, flanked by two poly(ethylene oxide)-blocks
Implementation Method 2
flubendazole solid particles having a particle size distribution in which D50 ≤ 0.45 micrometer and ≥ 90 % of particles are ≤ 1.0 micrometer
Data Source
AI summary
The present invention relates to a pharmaceutical aqueous suspension comprising: at most 35 wt.% of flubendazole, based on the weight of the pharmaceutical aqueous suspension, as solid particles having a particle size distribution in which D50 ≤ 0.45 micrometer and ≥ 90 % of particles are ≤ 1.0 micrometer; a non-ionic triblock copolymer surfactant comprising a central polypropylene oxide)-block having at least 30 propylene oxide (PO) units, flanked by two poly(ethylene oxide)-blocks, each having at a certain number of ethylene oxide (EO) units, wherein the ratio of number of PO units to total number of EO units is at least 0.2, one or more preservatives, and water. In addition, the present invention relates to a medicated water and a concentrated water comprising water and the pharmaceutical aqueous suspension as well as to a process of preparing a pharmaceutical aqueous suspension and to a use of the pharmaceutical aqueous suspension for the treatment of internal parasites in mammals, such as poultry and pigs.