Transdermal therapeutic system containing asenapine
Inventors
Mohr, Patrick • RIETSCHER, René • Eifler, René • BOURQUAIN, Olga
Assignees
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Publication Number
US-12138353-B2
Publication Date
2024-11-12
Expiration Date
Abstract
The present invention relates to transdermal therapeutic systems (TTS) for the transdermal administration of asenapine comprising a self-adhesive layer structure containing a therapeutically effective amount of asenapine, such asenapine TTS for use in a method of treatment, processes of manufacture of such TTS as well as asenapine and transdermal therapeutic systems containing asenapine for use in a method of treatment and to a method of treating a human patient by transdermal administration of asenapine.
Core Innovation
The invention relates to a self-adhesive transdermal therapeutic system for the transdermal administration of asenapine. The transdermal therapeutic system comprises a self-adhesive layer structure including an asenapine-containing matrix layer comprising asenapine and a polymer, and provides passive transdermal delivery of asenapine to systemic circulation.
The system is defined by a release area of from 10 to 80 cm2 and by quantitative composition and layer weight parameters, including an amount of asenapine in the asenapine-containing matrix layer ranging from 2% to 20% by weight and an area weight ranging from 90 to 230 g/m2. The performance is further characterized by a mean transdermal asenapine release rate of 0.5 to 20 mg/day and an asenapine Cmax value of from 0.5 to 10 ng/ml.
The disclosed approach also emphasizes a skin permeation rate measured in a Franz diffusion cell with dermatomed human skin across time intervals up to 72 hours. The invention additionally emphasizes formulation design choices, including avoidance of isopropyl palmitate and isopropyl myristate, preference for asenapine as the asenapine free base with a high mol% free base, and medical uses for treating psychosis conditions including schizophrenia and bipolar disorder.
Claims Coverage
The independent claim specifies a transdermal therapeutic system and imposes five inventive features, including a self-adhesive matrix-layer structure with quantitative physicochemical parameters and quantitative release, pharmacokinetic, and Franz diffusion skin-permeation performance.
Self-adhesive matrix-layer transdermal system for asenapine
A transdermal therapeutic system for the transdermal administration of asenapine comprising a self-adhesive layer structure containing asenapine, the self-adhesive layer structure comprising an asenapine-containing matrix layer comprising asenapine and a polymer.
Specified release area, asenapine loading, and matrix area weight
The transdermal therapeutic system has an area of release of from 10 to 80 cm2; the amount of asenapine in the asenapine-containing matrix layer ranges from 2% to 20% by weight; and the asenapine-containing matrix layer has an area weight ranging from 90 to 230 g/m2.
Quantitative mean transdermal release rate
The transdermal therapeutic system provides a mean transdermal asenapine release rate of 0.5 to 20 mg/day.
Quantitative skin permeation performance in Franz diffusion cells
The transdermal therapeutic system provides a skin permeation rate of asenapine as measured in a Franz diffusion cell with dermatomed human skin of 0 μg/(cm2·h) to 10 μg/(cm2·h) in the first 8 hours; 2 μg/(cm2·h) to 20 μg/(cm2·h) from hour 8 to hour 24; 3 μg/(cm2·h) to 20 μg/(cm2·h) from hour 24 to hour 32; 3 μg/(cm2·h) to 20 μg/(cm2·h) from hour 32 to hour 48; and 2 μg/(cm2·h) to 15 μg/(cm2·h) from hour 48 to hour 72.
Quantitative asenapine Cmax after transdermal administration
The transdermal therapeutic system provides an asenapine Cmax value of from 0.5 to 10 ng/ml following administration of the transdermal system to the skin of a subject in need thereof.
Overall, the claims cover a self-adhesive transdermal therapeutic system with an asenapine-containing matrix layer and specified area, loading, and matrix area weight, together with quantitative release, Cmax, and time-segmented Franz diffusion skin permeation performance.
Stated Advantages
Improved systemic/oral tolerability compared to marketed sublingual asenapine, while maintaining therapeutic exposure over the wear period.
Provides reduced asenapine-related side effects versus equivalent sublingual dosing.
Documented Applications
Transdermal administration of asenapine using a transdermal therapeutic system (TTS).
Evaluation of asenapine-containing transdermal therapeutic systems for skin permeation using Franz diffusion cells with dermatomed Gf6ttingen minipig skin and dermatomed human skin under OECD methodology.
Pharmacokinetic and safety assessment of transdermal asenapine TTS in Gf6ttingen minipigs, including plasma concentration metrics, patch residual drug, skin irritation scoring, and histopathology.
Human Phase I comparison of transdermal asenapine TTS versus marketed sublingual asenapine tablets, including plasma PK profiling, PK parameter estimates, metabolite exposure, and adverse event findings.
Treatment of psychosis conditions including schizophrenia.
Treatment of bipolar disorder, including acute manic or mixed episodes.
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