Thyroid Hormone Soft Capsule Stability via High-Amylose Starch

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Solution Overview

Problem

Thyroid hormones like thyroxine and triiodothyronine are chemically unstable when stored in soft capsules due to factors such as heat, light, air exposure, and humidity, leading to degradation and reduced therapeutic efficacy, especially since they are effective at low doses.

Innovation Solution

Incorporating high-amylose starch into the fill of soft capsules, optionally with vegetable hydrocolloids and glycerol, to stabilize thyroxine and triiodothyronine, ensuring their structural integrity and effectiveness during storage and administration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If thyroid hormones are stored in soft capsules, then they can be administered in liquid or semi-liquid form for better dissolution and absorption, but they degrade due to permeability to oxygen and absorption of moisture from the environment

Engineering Contradiction:
Improvedissolution and absorptionVSAvoidstability
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent introduces anhydrous substances (desiccants) as intermediary agents within the capsule fill that actively absorb moisture from the environment and prevent it from reaching the thyroid hormone. This mediator protects the hormone from degradation while maintaining the liquid/semi-liquid formulation benefits.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The capsule fill is formulated as a composite system combining the thyroid hormone, liquid/semi-liquid vehicle, and anhydrous stabilizing substances. This composite structure provides both the dissolution benefits of liquid formulation and the stability protection of moisture-absorbing materials.

Inventive Principle:
Principle #40Composite materials

2Measurement precision

If soft capsules are used for thyroid hormones, then dosing accuracy is improved through uniform distribution in liquid vehicle, but the capsules absorb moisture and facilitate hormone degradation

Engineering Contradiction:
Improvedosing accuracyVSAvoidmoisture absorption
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

Anhydrous substances serve as intermediary protective agents that intercept moisture before it can reach the hormone, thereby preventing degradation while preserving the dosing accuracy benefits of liquid formulation.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The inclusion of anhydrous substances creates a locally inert (dry) environment within the capsule fill, protecting the moisture-sensitive thyroid hormone from environmental humidity while maintaining formulation uniformity.

Inventive Principle:
Principle #39Inert atmosphere (Inert environment)

3Productivity

If thyroid hormones are stored in soft capsules with standard fill, then they can be administered effectively, but impurities form and titre reduces over time during storage

Engineering Contradiction:
Improvetherapeutic efficacyVSAvoidtitre maintenance
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The anhydrous substances are incorporated into the capsule fill during manufacturing, performing preliminary protection against moisture before storage begins. This preventive action maintains hormone titre and prevents impurity formation throughout the storage period.

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent converts the potentially harmful effect of moisture absorption into a beneficial protective mechanism by using the moisture-absorbing properties of anhydrous substances to shield the hormone from degradation, thereby maintaining therapeutic efficacy.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

Data Source

PatentUS11717486B2Highly stable formulations of thyroid hormone in soft capsules
Publication Date: 2023.08.08 IBSA INSTITUT BIOCHIMIQUE SA

AI summary

New soft capsules are described having within them a fill which contains thyroid hormones such as thyroxine T4 or triiodothyronine T3) and a high amylose-starch, optionally associated with vegetable hydrocolloids and/or glycerol. Compared to traditional capsules, these capsules have a strong and unexpected increase in the stability of T4 or T3 during storage.