Asenapine Patch Adhesive Composition for N-Oxide Suppression
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Solution Overview
Problem
Asenapine can be oxidized to generate asenapine-N-oxide during the manufacturing process of patches, which reduces the stability and effectiveness of the patch over time.
Innovation Solution
Incorporating thiosulfates, sulfites, or pyrosulfites into the adhesive composition of the patch, which includes asenapine or its pharmaceutically acceptable salt and an adhesive base, to suppress the generation of asenapine-N-oxide.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If asenapine is used in patch manufacturing without additional stabilizing agents, then the manufacturing process is simple, but asenapine-N-oxide is generated during manufacturing and storage, reducing product stability
Solution Approach 1:
Thiosulfates, sulfites, or pyrosulfites are introduced as intermediary substances that mediate between asenapine and oxidizing agents. These additives preferentially react with oxidizing agents or create a reducing environment, preventing direct oxidation of asenapine to asenapine-N-oxide while maintaining manufacturing simplicity
Solution Approach 2:
The chemical environment parameters of the adhesive composition are changed by adding thiosulfates, sulfites, or pyrosulfites. These substances alter the oxidation-reduction potential and chemical reactivity parameters of the system, creating conditions that suppress asenapine oxidation while maintaining manufacturing process simplicity
2Ease of operation
If asenapine is stored in patch form without stabilizing agents, then storage handling is simple, but asenapine-N-oxide accumulates over time, reducing pharmacological effectiveness
Solution Approach 1:
Thiosulfates, sulfites, or pyrosulfites are incorporated into the adhesive composition during manufacturing as preliminary protective measures. These substances are pre-positioned to act against potential oxidation during storage, preventing asenapine-N-oxide formation before it can occur during the storage period
Solution Approach 2:
The potential harmful oxidation that would normally occur during storage is converted into a beneficial protective mechanism. Thiosulfates, sulfites, or pyrosulfites act as sacrificial reducing agents that can be oxidized instead of asenapine, transforming the harmful oxidative environment into a protected state that maintains pharmacological effectiveness
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 addition of thiosulfates, sulfites, or pyrosulfites effectively reduces the generation of asenapine-N-oxide to 0.05% or less immediately after patch manufacture and 0.25% or less after storage, thereby maintaining the patch's stability and pharmacological effectiveness.
Implementation Method 1
Asenapine can be oxidized to generate asenapine-N-oxide in the process of manufacturing the patch
Implementation Method 2
adding at least one selected from the group consisting of thiosulfates, sulfites, and pyrosulfites to a composition comprising an adhesive base and asenapine or a pharmaceutically acceptable salt thereof
Data Source
AI summary
The present invention provides a patch comprising an adhesive layer on a backing, the adhesive layer comprising: asenapine or a pharmaceutically acceptable salt thereof; an adhesive base; and at least one selected from the group consisting of thiosulfates, sulfites, and pyrosulfites.