Sorbitan Ester Injectable Suspensions for Lower Tissue Irritation

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Solution Overview

Problem

Existing antipsychotic drugs like aripiprazole and olanzapine cause significant tissue irritation and poor patient compliance due to their injectable formulations, particularly in extended release forms, and there is a need for improved pharmaceutical compositions that mitigate these issues.

Innovation Solution

The development of pharmaceutical compositions comprising water-insoluble antipsychotic agents, such as aripiprazole and olanzapine, combined with sorbitan esters of carboxylic acids, particularly sorbitan laurate, and polyoxyethylene derivatives like polysorbate 20, forming an aqueous, flocculated injectable suspension that reduces tissue reaction and improves resuspendability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If aripiprazole is administered via intramuscular injection for extended release, then patient compliance is improved, but tissue irritation and adverse site reactions occur

Engineering Contradiction:

Improvepatient complianceVSAvoidtissue irritation

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses sulfobutylether beta-cyclodextrin as an intermediary substance to complex with aripiprazole, forming a soluble complex that can be administered via injection without causing tissue irritation. The cyclodextrin acts as a mediator that allows the drug to be delivered in a form that is both injectable and biocompatible

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the physical-chemical parameters of aripiprazole by forming a complex with cyclodextrin, transforming it from an insoluble form that causes irritation into a soluble complex that can be safely injected. This parameter change enables extended release administration while avoiding tissue reactions

Inventive Principle:

Principle #35Parameter changes

2Reliability

If olanzapine is formulated for extended release injection, then patient compliance is improved, but adverse site reactions occur

Engineering Contradiction:

Improvepatient complianceVSAvoidadverse site reactions

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent employs sulfobutylether beta-cyclodextrin as an intermediary to complex with olanzapine, creating a soluble complex suitable for intramuscular injection. The cyclodextrin mediator enables the drug to be delivered in an extended-release format without the tissue irritation associated with conventional formulations

Inventive Principle:

Principle #24Intermediary (Mediator)

3Object-affected harmful factors

If aripiprazole is complexed with sulfobutylether beta-cyclodextrin for injection, then tissue irritation is reduced, but formulation challenges arise due to poor solubility at neutral pH

Engineering Contradiction:

Improvetissue irritationVSAvoidformulation challenges

Core Design Contradiction:

Object-affected harmful factorsVSEase of manufacture

Solution Approach 1:

The patent adjusts the pH parameter of the formulation to enhance the solubility of the aripiprazole-cyclodextrin complex. By optimizing pH conditions, the formulation achieves both reduced tissue irritation and improved manufacturability, overcoming the solubility challenges at neutral pH

Inventive Principle:

Principle #35Parameter changes

4Duration of action of moving object

If water-insoluble antipsychotic agents are used for extended release, then dosing frequency is reduced, but resuspendability and stability are compromised

Engineering Contradiction:

Improvedosing frequencyVSAvoidresuspendability

Core Design Contradiction:

Duration of action of moving objectVSEase of operation

Solution Approach 1:

The patent uses surfactants and stabilizers as intermediary substances to improve the resuspendability of water-insoluble antipsychotic agents. These additives form stable suspensions that maintain drug stability while allowing easy resuspension, enabling extended-release dosing without compromising operational ease

Inventive Principle:

Principle #24Intermediary (Mediator)

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 compositions provide reduced tissue irritation and improved patient compliance by enhancing the resuspendability and injectability of antipsychotic drugs, allowing for easier administration and minimizing adverse reactions at the injection site.

Implementation Method 1

The development of pharmaceutical compositions incorporating sorbitan esters of carboxylic acids, specifically sorbitan laurate and polysorbate 20, which form an aqueous, flocculated, injectable suspension

Methodology Applied

Scientific EffectFlocculation: Flocculation

Data Source

PatentUS12629366B2Pharmaceutical compositions comprising sorbitan esters

Publication Date: 2026.05.19 ALKERMES PHARMA IRELAND LTD

AI summary

The present invention relates to a pharmaceutical composition comprising sorbitan esters of carboxylic acids that are useful for the delivery of anti-psychotic drugs.