Transdermal Patch Adhesive Matrix for Liquid Drug Stability
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Solution Overview
Problem
Transdermal drug delivery devices face challenges with drugs that are liquid at room temperature, including drug loss during manufacturing and adhesive failure due to plasticizing effects, which complicates the production process and affects the efficacy and comfort of the patches.
Innovation Solution
A monolithic transdermal device with an adhesive matrix layer containing selegiline or rivastigmine, an acrylic polymer pressure-sensitive adhesive without cross-linking agents, and a non-volatile coadjuvant like squalene, which maintains adhesive properties and minimizes drug loss during manufacturing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If liquid drugs are incorporated in transdermal devices, then transdermal delivery is achieved, but drug loss occurs during drying step in manufacture
Solution Approach 1:
A salt form of the liquid drug is used as an intermediary carrier during manufacturing. The salt is non-volatile and remains stable during the drying step, preventing drug loss. During skin penetration, the salt dissociates to release the active liquid drug, ensuring both manufacturing stability and therapeutic efficacy.
2Reliability
If liquid drugs are incorporated in transdermal devices, then transdermal delivery is achieved, but adhesive and wearing properties fail due to plasticizing effect
Solution Approach 1:
The salt form acts as a non-plasticizing intermediary carrier. Since salts of liquid drugs are non-volatile and non-plasticizing, they do not compromise the adhesive properties of the polymer matrix. The salt remains stable during manufacturing and only releases the active drug during skin penetration, preserving adhesive strength throughout the device lifecycle.
3Loss of substance
If multi-layer systems are used to avoid drug loss, then drug stability is improved, but cost and manufacturing complexity increase
Solution Approach 1:
The physical state of the drug is changed from liquid to salt form during manufacturing. This parameter change allows the drug to be incorporated in a single layer without losing volatility issues. The salt form provides stability during manufacturing, and the active drug is released during skin penetration, eliminating the need for multi-layer systems while maintaining drug stability.
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 solution allows for a simple, effective, and comfortable transdermal delivery of therapeutically acceptable doses of selegiline and rivastigmine with reduced skin irritation and improved adhesion, while minimizing drug loss and maintaining adhesive performance.
Implementation Method 1
a partial loss of the active drug during a drying step in the manufacture of the patches, which is usually performed between 50-100°C
Implementation Method 2
Another problem related to many drugs which are liquid at 25°C is their plasticizing effect on the polymer matrix which results in the failure of adhesive and wearing properties
Data Source
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AI summary
A monolithic device for transdermal administration of an active pharmaceutical ingredient which is selected from propargylamines and rivastigmine and is liquid at 25°C, has an adhesive matrix layer which includes the active ingredient in an acrylic polymer pressure sensitive adhesive without cross-linker agent containing a metal atom, the adhesive having a shear value of between 1.5 and 15 hours, and further includes a non-volatile coadjuvant selected from squalene and triethylcitrate present in the layer in an amount of 1 to 15wt%. The combination provides good release of the drug in use, reduces loss of the drug during a drying step in manufacture, reduces chemical interaction of the layer with the drug and achieves low level of skin irritation.