ASA Soft Gelatin Capsule Stabilization with High-Amylose Starch

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Solution Overview

Problem

Existing pharmaceutical formulations of acetylsalicylic acid (ASA) in soft gelatin capsules suffer from instability due to hydrolysis, and current solutions using cyclodextrins are costly, necessitating a stable and cost-effective alternative.

Innovation Solution

Incorporating high-amylose starches with 40-90% amylose content, in combination with organic acids like citric acid, into the soft capsule formulation to stabilize ASA and improve the stability of omega-3 fatty acids, preventing hydrolysis and maintaining stability during storage.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If cyclodextrins are used to stabilize ASA in soft capsules, then stability of ASA is improved, but manufacturing cost increases

Engineering Contradiction:
Improvestability of ASAVSAvoidmanufacturing cost
Core Design Contradiction:
Stability of the object's compositionVSEase of manufacture

Solution Approach 1:

The patent replaces expensive cyclodextrins with inexpensive, readily available excipients such as microcrystalline cellulose, silicon dioxide, and magnesium stearate. These common pharmaceutical excipients achieve the same stabilization effect against hydrolysis without the high cost associated with cyclodextrins, making the formulation economically viable for mass production

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The patent optimizes the formulation by controlling moisture content at less than 5% and adjusting the pH to between 3-5 using organic acids. These parameter changes create an environment that prevents ASA hydrolysis without requiring expensive stabilizing agents, thereby resolving the contradiction between stability and cost

Inventive Principle:
Principle #35Parameter changes

2Ease of operation

If ASA is formulated in soft gelatin capsules, then ease of administration is improved, but stability of ASA deteriorates due to hydrolysis

Engineering Contradiction:
Improveease of administrationVSAvoidstability of ASA
Core Design Contradiction:
Ease of operationVSStability of the object's composition

Solution Approach 1:

The patent introduces organic acids (such as citric acid, tartaric acid, or ascorbic acid) as intermediary substances that lower the pH to 3-5, creating an acidic environment that suppresses the hydrolysis of ASA. This intermediary acid acts as a protective mediator between the ASA and the hydrolytic conditions in the soft capsule, allowing the capsule form to be maintained while preventing degradation

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent creates an inert microenvironment within the soft capsule by maintaining low moisture content (less than 5%) and acidic pH conditions. This inert environment prevents water from participating in the hydrolysis reaction, thereby stabilizing ASA while preserving the advantageous ease of administration provided by the soft capsule form

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

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 high-amylose starches and organic acids results in a stable ASA formulation with less than 3% degradation after 36 months, suitable for antiplatelet and heart health applications, offering a cost-effective and efficient solution to the stability issues of ASA in soft gelatin capsules.

Implementation Method 1

the presence of amylose or starches containing between 40% and 90% amylose in the soft capsules protects the ASA against hydrolysis to SA

Methodology Applied
Scientific EffectHydrolysis prevention: Hydrolysis

Data Source

PatentUS9314435B2Stable formulations of antiplatelet agents, omega-3 fatty acids and amylose in soft gelatin capsules
Publication Date: 2016.04.19 IBSA INSTITUT BIOCHIMIQUE SA

AI summary

The invention discloses stable formulations of acetylsalicylic acid or salts thereof, omega-3 fatty acids and amylose in soft gelatin capsules.