Asenapine Transdermal Patch Formulation for Plasma Concentration Control
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Solution Overview
Problem
Conventional pharmaceutical preparations containing asenapine face challenges in maintaining a therapeutically effective plasma concentration while minimizing the concentration of its metabolite, leading to increased adverse effects.
Innovation Solution
A patch comprising a support layer and an adhesive agent layer with asenapine, isopropyl palmitate, and an adhesive base agent, specifically formulated to enhance skin permeability and reduce metabolite plasma concentration, with a preferred mass ratio of asenapine to isopropyl palmitate and inclusion of sodium diacetate.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If conventional topical agents containing asenapine are used, then the drug can be administered topically, but it is difficult to maintain a therapeutically effective plasma concentration of asenapine
Solution Approach 1:
The patent changes the chemical parameters of the formulation by incorporating specific organic acids (acetic acid, lactic acid, propionic acid) and their salts, along with absorption enhancers, to modify the skin permeability characteristics of asenapine. This enables the drug to achieve therapeutically effective plasma concentrations through topical application that were previously unattainable with conventional formulations.
2Quantity of substance
If the amount of asenapine shifted into plasma is increased to achieve therapeutic effect, then the plasma concentration of asenapine improves, but the plasma concentration of asenapine metabolite increases, leading to increased adverse effects
Solution Approach 1:
The patent introduces organic acids and their salts as intermediary substances that modify the drug's permeation characteristics. These intermediaries enhance the skin permeability of asenapine itself while appearing to suppress or minimize the formation and plasma concentration of its metabolite, thereby achieving therapeutic effects with reduced adverse effects.
3Quantity of substance
If conventional patches with absorption enhancers are used, then skin permeability is improved, but no specific formulation achieves both high asenapine plasma concentration and low metabolite plasma concentration
Solution Approach 1:
The patent creates a composite formulation combining asenapine with specific organic acids (acetic acid, lactic acid, propionic acid), their salts, and absorption enhancers in defined ratios. This composite material achieves synergistic effects that simultaneously enhance skin permeability and control metabolite formation, a result not achieved by conventional single-component or simple mixture formulations.
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 patch achieves a significantly higher therapeutically effective plasma concentration of asenapine while suppressing the plasma concentration of its metabolite, thereby reducing adverse effects.
Implementation Method 1
incorporating a combination of asenapine and/or a pharmaceutically acceptable salt thereof, isopropyl palmitate, and an adhesive base agent into an adhesive agent layer of a patch comprising a support layer and the adhesive agent layer enables the skin permeability of asenapine to be sufficiently high
Implementation Method 2
the adhesive agent layer comprises asenapine and/or a pharmaceutically acceptable salt thereof, isopropyl palmitate, and an adhesive base agent
Data Source
AI summary
A patch for administering asenapine includes a support layer, and an adhesive agent layer formed on the support layer and including an adhesive base agent and asenapine and/or a pharmaceutically acceptable salt thereof. The adhesive base agent has a content in a range of 10 to 90% by mass in the adhesive agent layer and includes a natural rubber, polyisobutylene, an alkyl vinyl ether(co)polymer, polyisoprene, polybutadiene, a styrene-butadiene copolymer, a styrene-isoprene copolymer, a styrene-isoprene-styrene block copolymer, or a combination thereof. When a content of the asenapine and/or pharmaceutically acceptable salt thereof in terms of free asenapine in the adhesive agent layer is 3.4 mg, an AUC2-120 for a period starting from the time when the patch is brought into contact with a skin for 24 hours is 27,000 pg·hr/mL or more, and an AUC2-120 of an asenapine metabolite is 20% or less of the AUC2-120 of the free asenapine.