Treprostinil Transdermal Patch SEDDS Formulation
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Solution Overview
Problem
Current treatments for pulmonary hypertension, particularly those involving treprostinil, face challenges such as low oral bioavailability, short systemic half-life, painful administration routes, and lung irritation, leading to discomfort and inefficiency.
Innovation Solution
Development of dermal and transdermal administration methods for treprostinil and its salts using transdermal patches with chemical or physical enhancement techniques to increase skin permeability, allowing for passive or active delivery without significant skin irritation, and potentially combining with additional therapeutic agents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If treprostinil is administered orally, then the administration is non-invasive and convenient, but the oral bioavailability is less than 10% and systemic half-life is very short
Solution Approach 1:
The patent uses a self-emulsifying drug delivery system (SEDDS) as an intermediary carrier to solubilize treprostinil in the gastrointestinal tract. The SEDDS formulation contains oils, surfactants, and co-solvents that form fine emulsion droplets, increasing the drug's solubility and absorption surface area, thereby dramatically improving oral bioavailability while maintaining the convenience of oral administration
2Reliability
If treprostinil is administered by intravenous or subcutaneous injection, then the systemic availability is high, but the administration causes pain at the injection site and risk of infection
Solution Approach 1:
The patent extracts the harmful aspects of parenteral administration (needle puncture, injection pain, infection risk) by completely eliminating the injection route. Instead, it delivers treprostinil through the gastrointestinal tract using an oral SEDDS formulation, achieving systemic availability through enhanced intestinal absorption without any parenteral intervention
3Ease of operation
If treprostinil is administered by inhalation, then the administration is non-invasive, but about 50% of patients experience lung irritation and the plasma concentration shows large peak-to-trough ratio
Solution Approach 1:
The patent replaces the lung delivery route with an gastrointestinal delivery route using SEDDS as an intermediary system. This avoids direct contact with lung tissue, eliminating the 50% incidence of lung irritation. The SEDDS formulation ensures controlled release and absorption in the GI tract, providing more stable plasma concentrations without the peak-to-trough fluctuations seen with inhalation
4Reliability
If chemical permeation enhancers are used in transdermal patches, then the skin permeability is increased, but the skin irritation may increase
Solution Approach 1:
The patent employs a composite SEDDS formulation containing multiple components working synergistically: oils (for solubility), surfactants (for emulsification and mild penetration enhancement), and co-solvents. This composite approach achieves effective drug delivery while the surfactants are selected to minimize skin irritation compared to traditional strong permeation enhancers
Solution Approach 2:
The patent changes the physical state and composition parameters of the drug delivery system by using self-emulsifying formulations that transform from a separate liquid phase into fine emulsion droplets upon contact with gastrointestinal fluids. This parameter change (from macroscopic liquid to microscopic emulsion droplets) dramatically increases the surface area for absorption and drug solubility without requiring harsh permeation enhancers
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
Enhances local or systemic availability of treprostinil, reducing discomfort, minimizing lung irritation, and providing a more uniform plasma concentration, thus improving treatment efficacy and patient compliance.
Implementation Method 1
A transdermal patch can be designed to deliver treprostinil or a salt thereof passively (passive transport of treprostinil as the carboxylic acid in some embodiments)
Implementation Method 2
A transdermal patch can be designed to deliver treprostinil or a salt thereof passively (passive transport of treprostinil as the carboxylic acid in some embodiments), optionally with the use of one or more chemical permeation enhancers
Implementation Method 3
optionally with the use of one or more chemical permeation enhancers
Implementation Method 4
or actively with the assistance of a physical enhancement technique (e.g., an iontophoretic patch, a sonophoretic patch, a microneedles patch or a patch to which high pressure is applied)
Implementation Method 5
or actively with the assistance of a physical enhancement technique (e.g., an iontophoretic patch, a sonophoretic patch, a microneedles patch or a patch to which high pressure is applied)
Implementation Method 6
or actively with the assistance of a physical enhancement technique (e.g., an iontophoretic patch, a sonophoretic patch, a microneedles patch or a patch to which high pressure is applied)
Data Source
AI summary
The present disclosure provides methods, compositions, devices and systems for dermal and transdermal administration of treprostinil or salts thereof, and optionally an additional therapeutic agent. Treprostinil and salts thereof can be dermally or transdermally administered to treat any medical conditions responsive to treatment with treprostinil, including pulmonary hypertension, such as pulmonary arterial hypertension.