Transdermal Patch Using Oxide Salt Conversion for Drug Flux Control
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Solution Overview
Problem
Transdermal therapeutic systems using active pharmaceutical ingredients in their free base form face stability issues, such as chemical degradation, physical softness, and 'cold flow,' while using salts improves stability but reduces skin permeability, necessitating complex control membranes to regulate flux rates.
Innovation Solution
A transdermal therapeutic system employing a pharmaceutically acceptable salt of the active substance in combination with an oxide that reacts with skin moisture to form a hydroxide, converting the salt into its free base and controlling drug release through an acid-base reaction, eliminating the need for a control membrane.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If active substance is used in free base form, then skin permeability is improved, but chemical stability deteriorates
Solution Approach 1:
The active substance is segmented into two functional components: a salt form embedded in the matrix that provides stability, and a hydroxide-generating agent (oxide) that converts it to the permeable free base form at the skin interface. This spatial and functional segmentation allows each component to optimize its role without compromise.
Solution Approach 2:
The oxide is pre-incorporated into the matrix along with the active substance salt. Upon application to the skin, the oxide automatically reacts with skin moisture to generate hydroxide ions, which then convert the salt to free base form. This preliminary positioning of conversion agents eliminates the need for external triggers and ensures timely activation.
2Ease of manufacture
If active substance is used in free base form, then ease of processing is improved, but physical stability deteriorates
Solution Approach 1:
The formulation segments the active substance into a stable salt form for processing and storage, while incorporating separate hydroxide-generating agents (oxides like CaO, MgO, BaO) that provide the necessary basic environment. This segmentation maintains physical stability during manufacturing while enabling free base formation for transdermal delivery.
Solution Approach 2:
The oxide acts as an intermediary substance that mediates between the stable salt form and the required free base form. It provides basicity indirectly through hydroxide generation from skin moisture, avoiding direct handling of volatile or unstable free base during processing while ensuring its availability at the application site.
3Manufacturing precision
If control membrane is added to regulate flux rate, then drug flux control is improved, but device complexity increases
Solution Approach 1:
The invention controls drug flux by changing the chemical parameters of the matrix system - specifically, by incorporating oxides in controlled amounts that generate hydroxide ions to convert salt to free base. The flux rate is regulated by the oxide concentration, particle size, and reactivity, eliminating the need for additional control membranes while maintaining precise delivery control.
Solution Approach 2:
The mechanical control system (control membrane) is replaced with a chemical control system based on acid-base reactions. The oxide-hydroxide-salt conversion mechanism inherently regulates free base availability and thus drug flux, substituting a complex mechanical barrier with a simpler chemical equilibrium approach that provides comparable or superior control.
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
This approach allows for controlled drug flux without additional membranes, enhancing stability and permeability while reducing production complexity and costs, with adjustable flux rates through concentration and layering strategies.
Implementation Method 1
the water coming out of the skin causes an acid-base reaction between the active substance salt and the hydroxide formed from the oxide, in which the active substance in the form of its free base as a reaction product from the TTS can be released
Implementation Method 2
The humidity in the air can lead to hydrolysis of the active ingredient base
Data Source
AI summary
The present invention relates to transdermal therapeutic systems, comprising an occlusive back layer impervious to an active substance, a single or multilayer matrix, and a peelable protective film, wherein the matrix or at least one of the matrix layers comprises a pharmaceutical active substance or a plurality of pharmaceutical active substances in the form of at least one pharmaceutically consumable salt thereof, and a pharmaceutically consumable, alkaline reacting oxide.