Apomorphine Transdermal Formulation for High-Concentration Permeation
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Solution Overview
Problem
Existing transdermal formulations fail to dissolve apomorphine at high concentrations necessary for rapid and sustained skin permeation, particularly for nighttime and early morning off-symptoms in Parkinson's disease, and there is a need for continuous administration.
Innovation Solution
A transdermal formulation combining a specific polyhydric alcohol and propylene carbonate allows apomorphine or its salt to be dissolved at concentrations of 5% by weight or more, enabling rapid and continuous transdermal administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If a transdermal formulation is designed for rapid and sustained skin permeation of apomorphine, then the drug concentration in the formulation must be high, but no method has been developed to dissolve apomorphine at sufficient concentration
Solution Approach 1:
The patent uses a composite solvent system combining propylene carbonate (a polar aprotic solvent) with polyhydric alcohols (such as glycerin, propylene glycol, or butanediol). This composite approach leverages the high solvating power of propylene carbonate for apomorphine while the polyhydric alcohols enhance solubility through hydrogen bonding and reduce the formulation's overall polarity, enabling dissolution of apomorphine at concentrations of 5% or higher by weight
Solution Approach 2:
The patent changes the chemical composition parameters of the solvent system by introducing specific ratios of propylene carbonate to polyhydric alcohols. By adjusting the concentration of apomorphine, the types and proportions of polyhydric alcohols, and the pH of the formulation, the patent achieves optimal solubility and skin permeation properties that were not attainable with conventional single-solvent systems
2Speed
If subcutaneous injection is used for rapid improvement of off-symptoms, then the drug acts quickly, but administration is difficult at night or early in the morning when patients experience off-symptoms
Solution Approach 1:
The patent replaces the mechanical injection system (subcutaneous injection requiring needle insertion and manual administration) with a transdermal delivery system that utilizes the skin's natural permeability. The formulation is applied topically and allows passive diffusion of apomorphine through the skin, eliminating the need for invasive procedures while maintaining therapeutic effectiveness
Solution Approach 2:
The patent introduces the transdermal formulation as an intermediary delivery system that bridges the gap between the need for rapid drug action and the convenience of non-invasive administration. The formulation contains apomorphine in a specialized solvent system that facilitates rapid skin permeation, serving as a mediator that delivers the drug systemically without requiring injection
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 formulation achieves rapid and sustained skin permeation of apomorphine, ensuring a sufficient amount is absorbed into the body in a short time and can be administered continuously.
Implementation Method 1
a solution containing a high concentration of apomorphine or a salt thereof can be prepared by combining a specific polyhydric alcohol and propylene carbonate
Implementation Method 2
transdermal formulation that allows a sufficient amount of apomorphine to be absorbed into the body through the skin in a short time
Data Source
Figure 1~2
AI summary
The present invention aims to provide a transdermal formulation in which apomorphine or a salt thereof is dissolved at a high concentration, so that a sufficient amount of apomorphine for treatment can be absorbed in a short time, and can be administered continuously. The present invention can include, for example, a transdermal formulation, comprising apomorphine or a salt thereof, a polyhydric alcohol with a carbon number of 6 or less and/or a low molecular weight polyethylene glycol, and propylene carbonate. According to the present invention, it is possible to prepare a solution containing apomorphine in a high concentration, and to allow a sufficient amount of apomorphine to be absorbed into the body through the skin in a short time and administered continuously.