Pharmaceutical composition for nasal delivery
Inventors
Sävmarker, Jonas • Rönn, Robert • Fischer, Andreas
Assignees
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Publication Number
US-12268684-B2
Publication Date
2025-04-08
Expiration Date
Abstract
According to the invention, there is provided a solid pharmaceutical composition formulation for nasal delivery of an opioid antagonist, comprising a pharmacologically-effective amount of an opioid antagonist and a pharmaceutically-acceptable carrier. The compositions are preferably in the form of a powder produced by spray-drying, which are subsequently loaded into single use nasal applicators. Preferred pharmaceutically-acceptable carriers in this regard include disaccharides (e.g. lactose or trehalose) and dextrins (e.g. cyclodextrins or maltodextrins), preferably spray-dried together in combination. Compositions may further comprise an alkyl saccharide, preferably a sucrose ester, such as sucrose monolaurate. The compositions and applicators may be employed in the treatment of opioid overdose in subjects.
Core Innovation
The invention relates to a solid pharmaceutical composition in the form of a spray-dried powder for nasal delivery of nalmefene or a pharmaceutically-acceptable salt thereof. The composition comprises a pharmacologically-effective amount of nalmefene and a pharmaceutically-acceptable carrier material comprising a combination of a disaccharide selected from maltitol, trehalose, sucralose, sucrose, isomalt, maltose, and lactose, and a dextrin. The composition is essentially free of water and is suitable for nasal delivery.
A key aspect is chemical stability of nalmefene during storage. The composition includes a stability requirement that nalmefene or the pharmaceutically-acceptable salt is less than about 15% chemically degraded after storage for 3 months at 75% relative humidity and 40°C. The carrier design and low water content support stability, including defining carrier components as disaccharide together with a dextrin in a spray-dried solid state.
The disclosure also reports unexpected performance advantages relative to a reference nasal spray product. It describes improved chemical stability for certain disaccharides versus monosaccharides, improved physical stability when dextrins are spray-dried with disaccharides, and higher and/or more rapid nalmefene absorption in ex vivo nasal tissue permeation studies and in clinical pharmacokinetic studies versus Narcan® nasal spray.
Claims Coverage
The claims cover 2 inventive features.
Spray-dried essentially water-free nalmefene powder with disaccharide and dextrin carrier
A solid pharmaceutical composition in the form of a spray-dried powder comprising a pharmacologically-effective amount of nalmefene or a pharmaceutically-acceptable salt thereof and a pharmaceutically-acceptable carrier material comprising a combination of a disaccharide selected from maltitol, trehalose, sucralose, sucrose, isomalt, maltose, and lactose; and a dextrin, wherein the composition is essentially free of water and suitable for nasal delivery of nalmefene or the pharmaceutically-acceptable salt thereof.
Chemical degradation stability requirement for nasal nalmefene powder
The nalmefene or pharmaceutically-acceptable salt thereof is less than about 15% chemically degraded after storage for 3 months at 75% relative humidity and 40°C.
The claims center on the spray-dried, essentially water-free nalmefene composition with a disaccharide and dextrin carrier and the stated chemical degradation stability requirement.
Stated Advantages
Improved chemical stability for certain disaccharides versus monosaccharides.
Improved physical stability with dextrins when spray-dried with disaccharides.
Higher and/or more rapid nalmefene absorption in ex vivo nasal tissue permeation studies.
Higher and/or more rapid nalmefene absorption in clinical pharmacokinetic studies versus Narcan® nasal spray.
Documented Applications
Nasal delivery of nalmefene or pharmaceutically-acceptable salts using a solid spray-dried essentially water-free powder formulation.
Use in ex vivo nasal tissue permeation studies and clinical pharmacokinetic studies, with comparison to Narcan® nasal spray.
Solid-state stability during storage under humid conditions, including packaging/device concepts described to relate to reducing atmospheric water ingress.
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