Levothyroxine Reconstitution Kit Segmentation

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Solution Overview

Problem

The development of stable liquid formulations of levothyroxine is hindered by its instability in aqueous environments and high humidity, leading to degradation and precipitation issues, which limits the flexibility of dosing and increases storage and distribution costs, while solid dosage forms lack flexibility and uniformity.

Innovation Solution

A pharmaceutical system comprising a solid for reconstitution in the form of powder or granules, using sorbitol or maltodextrin as excipients, and an aqueous reconstitution liquid with polyvinyl pyrrolidone, allowing for stable reconstitution into a liquid solution that is free of organic solvents, facilitating flexible dosing and improved stability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If liquid formulations of levothyroxine are developed, then flexible dosing is achieved, but stability and precipitation issues occur

Engineering Contradiction:
Improvedosing flexibilityVSAvoidformulation stability
Core Design Contradiction:
Adaptability or versatilityVSStability of the object's composition

Solution Approach 1:

The formulation is divided into two separate components: a solid component containing levothyroxine and excipients, and a liquid component containing solubilizing agents. These components are mixed immediately before use, allowing flexible dosing while maintaining stability during storage of individual components separately.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The solid component is prepared in advance with levothyroxine dispersed in excipients, and the liquid component is prepared separately with solubilizing agents. This preliminary preparation allows both components to be stable during storage, and they are combined immediately before administration to ensure flexibility and stability.

Inventive Principle:
Principle #10Preliminary action

2Quantity of substance

If organic solvents are used in liquid formulations, then solubility is improved, but safety and acceptability for long-term use deteriorate

Engineering Contradiction:
ImprovesolubilityVSAvoidsafety for long-term use
Core Design Contradiction:
Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The formulation uses aqueous-based liquid component with solubilizing agents instead of organic solvents, changing the chemical parameter from organic to aqueous base. This maintains solubility while improving safety and acceptability for long-term thyroid hormone replacement therapy.

Inventive Principle:
Principle #35Parameter changes

3Stability of the object's composition

If low temperature storage is required, then stability is improved, but convenience and distribution costs deteriorate

Engineering Contradiction:
ImprovestabilityVSAvoidstorage convenience
Core Design Contradiction:
Stability of the object's compositionVSEase of operation

Solution Approach 1:

The formulation separates the levothyroxine into a solid component and the solubilizing agents into a liquid component, each stable at room temperature when stored separately. This eliminates the need for refrigeration during storage and distribution, improving convenience while maintaining stability.

Inventive Principle:
Principle #1Segmentation

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 system provides a stable reconstituted liquid solution that maintains the active ingredient's stability during storage, offers ease of administration, and eliminates the need for special storage conditions, ensuring uniformity and flexibility in dosing without the use of organic solvents.

Implementation Method 1

an aqueous reconstitution liquid with polyvinyl pyrrolidone, allowing for stable reconstitution into a liquid solution

Methodology Applied
Scientific EffectSolubilization: Solvation

Implementation Method 2

a solid for reconstitution in the form of powder or granules, using sorbitol or maltodextrin as excipients

Methodology Applied
Scientific EffectAdsorption: Adsorption

Data Source

PatentEP2692340B1Stable pharmaceutical system (kit) for the preparation of oral solution of levothyroxine or pharmaceutically acceptable salt thereof
Publication Date: 2015.03.11 VERISFIELD UK LDT

AI summary

The present invention relates to a stable pharmaceutical system (kit) for the preparation of oral solution of levothyroxine or pharmaceutically acceptable salt thereof, which consists of a solid for reconstitution in the form of powder or granules and of a reconstitution liquid. The solid for reconstitution further comprises at least one excipient - carrier of the active ingredient, preferably water soluble, more preferably sorbitol or maltodextrin or a mixture thereof. The reconstitution liquid is aqueous and comprises at least one excipient for the solubilization of the active ingredient, preferably polyvinylpyrrolidone and optionally at least one preservative.