Aripiprazole Transdermal Patch Formulation
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Solution Overview
Problem
Existing transdermal delivery systems for aripiprazole lack an effective solvent combination for optimal skin permeation, despite prior art describing permeation enhancers and nanoparticulate formulations.
Innovation Solution
A combination of NMP, DMSO, alcohol, and water with a gelling agent like Carbopol 971 in a range of concentrations is used to formulate aripiprazole liquid and gel formulations, optimized for enhanced skin permeation, along with fatty acid enhancers like Lauric and Myristic acid, and a pH range of approximately 6 to 7.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If aripiprazole is formulated in conventional transdermal patches with permeation enhancers, then skin permeation is improved, but the formulation lacks optimal solvent combination for maximum efficacy
Solution Approach 1:
The patent optimizes the solvent system by adjusting the concentration ratios of NMP, DMSO, alcohol, and water to achieve optimal skin permeation. The gel formulation uses Carbopol 971 at 0.5% with specific solvent combinations, while the liquid formulation uses NMP and DMSO in optimized proportions. This parameter optimization resolves the contradiction by finding the precise formulation that maximizes permeation without excessive complexity.
Solution Approach 2:
The patent creates composite formulations combining multiple solvents (NMP, DMSO, alcohol, water) with gelling agents (Carbopol 971) and permeation enhancers (fatty acids). This composite approach allows synergistic effects where each component contributes to different aspects of skin permeation, achieving reliable drug delivery through a coordinated multi-component system.
2Reliability
If nanoparticulate aripiprazole is used, then skin permeation is enhanced, but the formulation does not achieve consistent therapeutic blood levels
Solution Approach 1:
The patent optimizes formulation parameters including pH (adjusted to 6-7), solvent concentrations, and gel composition to ensure consistent drug permeation. By controlling these parameters, the formulation achieves reliable therapeutic blood levels with consistent permeation flux, resolving the contradiction between enhancement and consistency.
3Quantity of substance
If transdermal delivery is used to avoid hepatic first-pass effect, then bioavailability is improved, but the formulation requires optimal pH and solvent combination to achieve consistent permeation
Solution Approach 1:
The patent establishes specific parameter ranges including pH 6-7, NMP 40%, DMSO 40%, Alcohol 15%, and Water 5% for the liquid formulation, and Carbopol 971 0.5% for the gel formulation. These optimized parameters ensure consistent permeation and bioavailability while providing clear formulation guidelines that manage complexity through standardization.
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 optimized formulation achieves a consistent drug flux of 50mcg/cm²/h to 800mcg/cm²/h through human cadaver skin, ensuring effective therapeutic blood levels and improved medication compliance, particularly in the geriatric population by avoiding hepatic first-pass effect and simplifying administration.
Implementation Method 1
The optimized formulation achieves a consistent drug flux of 50mcg/cm²/h to 800mcg/cm²/h through human cadaver skin
Implementation Method 2
The gel formulation should contain a gelling agent in the range of about 0.1% to 5% W/V and the optimum APRZ composition should range from about 1% W/V to 20% W/V with about .5% W/V of the gelling agent
Implementation Method 3
The effect of enhancers on the flux of ARPZ through human cadaver skin was evaluated and is shown in Figure 3
Data Source
Figure 1
Figure 2
Figure 3
AI summary
The present invention discloses compositions of liquid and gel formulation containing aripiprazole in the form of a patch for transdermal delivery.