Transdermal Salt Formulation With In Situ Neutralization
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Solution Overview
Problem
Existing transdermal formulations face challenges in delivering active agents with low solubility and stability in their neutral form, leading to insufficient dosage and recrystallization issues, as well as instability over multiple days.
Innovation Solution
A composition comprising micronized particles of an amine salt form of the active agent dispersed in a drug reservoir with a proton accepting entity, such as sodium bicarbonate, and a salt form solubilizer, along with additional components like solubilizers and adhesives, to enhance skin permeability and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If the neutral form of the active agent is used to enhance skin permeability, then transdermal delivery efficiency is improved, but solubility in the drug reservoir becomes insufficient
Solution Approach 1:
The patent changes the chemical form of the active agent from neutral to salt form (parameter change), which fundamentally alters both solubility and skin permeability characteristics. The salt form provides high solubility in the drug reservoir while maintaining adequate skin permeability through the conversion mechanism
Solution Approach 2:
The patent introduces an intermediary conversion mechanism where the salt form of the active agent is converted to the neutral form at or near the skin interface. This intermediary step allows the system to benefit from both the high solubility of the salt form and the high permeability of the neutral form
2Speed
If the neutral form of the active agent is used to improve skin permeability, then transdermal delivery is enhanced, but stability of the active agent deteriorates
Solution Approach 1:
The patent changes the chemical form parameter of the active agent to the salt form, which fundamentally improves stability while maintaining transdermal delivery capability through the conversion mechanism
Solution Approach 2:
The active agent is prepared in the stable salt form beforehand (preliminary action), and the conversion to the permeable neutral form occurs only when needed at the application site, preventing degradation that would occur if the neutral form were present during storage and handling
3Quantity of substance
If sufficient amount of active agent is incorporated to deliver therapeutic level, then dosage requirement is met, but recrystallization occurs during solvation and drying
Solution Approach 1:
The patent changes the form of the active agent to salt form, which has different solubility and crystallization characteristics compared to the neutral form, allowing sufficient dosage incorporation without large crystal formation during processing
Solution Approach 2:
The patent creates local conditions in the drug reservoir that favor the salt form's solubility and prevent crystallization, while enabling conversion to the neutral form at the skin interface where it is needed for permeation
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 provides a steady and effective transdermal delivery of active agents, maintaining a consistent activity level over several days by converting the salt form to a more permeable neutral form, thereby overcoming solubility and stability issues.
Implementation Method 1
a proton accepting entity, such as sodium bicarbonate, and a salt form solubilizer
Implementation Method 2
micronized particles of an amine salt form of the active agent dispersed in a drug reservoir with a proton accepting entity, such as sodium bicarbonate, and a salt form solubilizer
Implementation Method 3
the active agent diffuses from the drug reservoir and into the skin
Data Source
Figure 1~3
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AI summary
Compositions, devices, and methods for transdermal administration of active agents provided in their salt form instead of neutral form are provided.