Fosfomycin Trometamol Tablet Formulation for Veterinary Use

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Solution Overview

Problem

Formulating fosfomycin trometamol tablets for veterinary use, particularly for companion animals like cats and dogs, is challenging due to high hygroscopicity and poor stability, which affects palatability and pharmacotechnical properties, and existing formulations with high active ingredient content result in large, unpalatable tablets.

Innovation Solution

The use of anhydrous calcium hydrogen phosphate and microcrystalline cellulose as diluents in fosfomycin trometamol formulations improves flow and compressibility, stability, and palatability, allowing for the creation of tablets with reduced excipient content and adaptable dosing based on animal weight.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If fosfomycin trometamol is formulated with high active ingredient content to reduce excipient amount, then the amount of excipients is reduced, but the tablet size becomes too large and palatability deteriorates

Engineering Contradiction:
Improveamount of excipientsVSAvoidtablet size
Core Design Contradiction:
Quantity of substanceVSShape

Solution Approach 1:

The tablet is divided into multiple segments or pieces with break marks, allowing the total dose to be divided into smaller, more palatable portions for veterinary administration while maintaining the required high active ingredient content

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The formulation changes the physical parameters of the tablet including size, shape, and incorporation of palatability enhancers to improve acceptance by animals while maintaining high fosfomycin trometamol content

Inventive Principle:
Principle #35Parameter changes

2Speed

If fosfomycin trometamol is formulated as a solution, then absorption rate is improved, but stability deteriorates due to high hygroscopicity and poor stability in water

Engineering Contradiction:
Improveabsorption rateVSAvoidstability in water
Core Design Contradiction:
SpeedVSStability of the object's composition

Solution Approach 1:

The formulation transitions from a liquid solution phase to a solid dispersed phase using superdisintegrants and specific excipients, maintaining rapid disintegration and absorption characteristics while achieving stability in the solid state for storage and administration

Inventive Principle:
Principle #36Phase transitions

3Stability of the object's composition

If fosfomycin trometamol is formulated as a granulate for human use, then stability is improved, but ease of operation deteriorates for veterinary use due to difficulty in dose adaptation

Engineering Contradiction:
ImprovestabilityVSAvoiddose adaptation
Core Design Contradiction:
Stability of the object's compositionVSEase of operation

Solution Approach 1:

The granulate formulation is divided into multiple tablets with break marks, enabling veterinarians to easily adapt the dose to animal weight by administering appropriate numbers of tablets or fractions thereof, while maintaining the stability benefits of the granulate structure

Inventive Principle:
Principle #1Segmentation

4Device complexity

If fosfomycin trometamol tablets are manufactured with no excipients other than lubricant, then manufacturing complexity is reduced, but manufacturing precision deteriorates due to lack of flow and compressibility properties

Engineering Contradiction:
Improveformulation complexityVSAvoidtablet weight uniformity
Core Design Contradiction:
Device complexityVSManufacturing precision

Solution Approach 1:

Superdisintegrants and specific excipients are introduced as intermediary substances that facilitate tablet manufacturing by improving flow and compressibility properties, enabling precise manufacturing while maintaining a relatively simple formulation overall

Inventive Principle:
Principle #24Intermediary (Mediator)

Data Source

PatentEP4043006B1New fosfomycin tablet formulations
Publication Date: 2023.12.06 LABIANA HEALTH SL
  • EP4043006B1 patent drawingFigure 1
  • EP4043006B1 patent drawingFigure 2a
  • EP4043006B1 patent drawingFigure 2b

AI summary

The present invention concerns tablet formulations of fosfomycin trometamol, methods of manufacturing and using thereof. More specifically, it relates to an oral pharmaceutical composition in tablet form comprising or consisting of: a. fosfomycin trometamol; b. a low moisture diluent selected from the group consisting of anhydrous calcium hydrogen phosphate, anhydrous microcrystalline cellulose and combinations thereof; c. optionally, a lubricant; and d. optionally, other pharmaceutically acceptable excipients.