Transdermal therapeutic system containing asenapine
Inventors
Mohr, Patrick • RIETSCHER, René • Eifler, René • BOURQUAIN, Olga
Assignees
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Publication Number
US-12329862-B2
Publication Date
2025-06-17
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 describes a transdermal therapeutic system for the transdermal administration of asenapine. The system includes a self-adhesive layer structure with a backing layer and an asenapine-containing matrix layer containing asenapine, a polymer selected from acrylic polymers, and medium chain triglycerides in an amount from 5 to 12% of the matrix layer, with specific fatty acid composition ranges for the medium chain triglycerides.
The transdermal therapeutic system further contains asenapine in an overall amount of from 0.82 mg/cm2 to 2.0 mg/cm2 and comprises a synergistic amount of ascorbyl palmitate and α-tocopherol. This stabilizer system improves storage stability and reduces amounts of asenapine N-oxides (cis/trans), tetradehydro-asenapine, and other related substances after storage under high humidity conditions.
The document also reports in vivo Phase I open-label evidence comparing relative bioavailability after single-dose administration of the transdermal therapeutic system versus marketed sublingual Sycrest® 5 mg asenapine maleate tablets. The transdermal therapeutic system maintains therapeutic plasma concentrations over the wear period, with lower and delayed Cmax and reduced major metabolite formation compared with sublingual administration.
Claims Coverage
The claims coverage is anchored by one independent claim. The principal inventive features total three elements: the self-adhesive layer structure with an asenapine-containing matrix layer; acrylic polymer selection with medium chain triglycerides of defined proportion and fatty-acid composition; and constrained asenapine loading with a synergistic ascorbyl palmitate and α-tocopherol stabilizer system.
Self-adhesive layer structure for transdermal asenapine delivery
A transdermal therapeutic system comprising a self-adhesive layer structure containing a therapeutically effective amount of asenapine, the self-adhesive layer structure comprising a backing layer and an asenapine-containing matrix layer.
Acrylic matrix with medium chain triglycerides at defined proportion and fatty-acid composition
An asenapine-containing matrix layer comprising asenapine, a polymer selected from acrylic polymers, and medium chain triglycerides in an amount of from 5 to 12% of the matrix layer, wherein the fatty acid composition of the medium chain triglycerides has specified composition sets including hexanoic acid, octanoic acid, decanoic acid, dodecanoic acid, and tetradecanoic acid.
Specified asenapine loading and synergistic antioxidant stabilizer system
The transdermal therapeutic system contains from 0.82 mg/cm2 to 2.0 mg/cm2 asenapine and comprises a synergistic amount of ascorbyl palmitate and α-tocopherol.
Overall, the claim coverage centers on a self-adhesive transdermal therapeutic system with an acrylic asenapine matrix using medium chain triglycerides defined by specific fatty-acid composition options, constrained asenapine loading per area, and an ascorbyl palmitate plus α-tocopherol synergistic stabilizer system.
Stated Advantages
Improves storage stability.
Limits degradation, including asenapine N-oxides (cis/trans), tetradehydro-asenapine, and other related substances after storage under high humidity.
Maintains therapeutic plasma concentrations over the wear period.
Shows lower and delayed Cmax versus marketed sublingual Sycrest® 5 mg.
Reduces major metabolite formation versus sublingual administration.
Reduces Cmax and fluctuation versus sublingual Sycrest 5 mg in a Phase I relative bioavailability study.
Altered metabolite exposure, including reduced N-desmethyl-asenapine and asenapine-glucuronide exposure versus the reference.
Fewer and/or reduced-intensity asenapine-related side effects, with good local tolerance.
Shows fewer and mostly mild adverse events versus sublingual administration.
Documented Applications
Transdermal administration of asenapine using the claimed transdermal therapeutic system, with clinical PK comparison to marketed sublingual Sycrest® 5 mg and in vivo Phase I relative bioavailability evidence.
Treatment of psychosis conditions, including schizophrenia, bipolar disorder and related disorders, and acute manic/mixed episodes.
Treatment of PTSD, major depressive disorder, dementia-related psychosis, and agitation.
Formulation storage under high humidity conditions, with reported reductions of asenapine N-oxides (cis/trans), tetradehydro-asenapine, and other related substances after storage.
System use with administration durations up to approximately 7 days, including example administration periods of 24 h to 168 h and exchange schedules.
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