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Publication Number
US-10898480-B1
Publication Date
2021-01-26
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 suitable for nasal delivery of naloxone or a pharmaceutically acceptable salt thereof for treating opioid overdose. The composition includes a pharmacologically-effective amount of naloxone or the salt together with a pharmaceutically acceptable carrier material comprising a disaccharide selected from maltitol, trehalose, sucralose, sucrose, isomalt, maltose, and lactose, together with a dextrin.
A key aspect of the formulation is chemical stability of naloxone under humidity and heat. The powder is characterized such that naloxone or the pharmaceutically acceptable salt thereof is less than about 15% chemically degraded after 3 months at 75% relative humidity and 40°C.
The invention further emphasizes performance outcomes for nasal delivery, including improved bioavailability and faster absorption compared with commercial naloxone nasal spray, supported by pharmacokinetics including AUC, Cmax, Tmax, and early AUC. The document also describes ex vivo porcine nasal tissue permeation and stability experiments for naloxone and nalmefene, including effects of carrier choice on chemical stability and impurity formation.
Claims Coverage
The independent claim covers a spray-dried nasal naloxone solid formulation with a specific carrier system and a required chemical-stability threshold under defined storage stress conditions. The cited independent claim is accompanied by dependent refinements specifying particle size and distribution parameters, particular disaccharide and dextrin embodiments, Tg behavior under humidity, and formulation, manufacturing, and nasal applicator-related features.
Spray-dried nasal naloxone powder with disaccharide plus dextrin carrier
A solid pharmaceutical composition in the form of a spray-dried powder suitable for nasal delivery of naloxone or a pharmaceutically acceptable salt thereof to treat opioid overdose, comprising a pharmacologically-effective amount of naloxone or the salt 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.
Chemical stability limit under humidity and heat
The spray-dried powder wherein the naloxone or the pharmaceutically acceptable salt thereof is less than about 15% chemically degraded after 3 months at 75% relative humidity and 40°C.
Overall, the claim coverage is anchored on a spray-dried nasal naloxone powder using a disaccharide-plus-dextrin carrier system together with a defined chemical degradation limit after storage at elevated relative humidity and temperature.
Stated Advantages
Improved physical and chemical stability, including chemical stability less than about 15% degradation after 3 months at 75% relative humidity and 40°C.
Enhanced bioavailability and faster absorption compared with commercial naloxone nasal spray, supported by pharmacokinetics including AUC and early AUC.
Documented Applications
Nasal delivery of naloxone or pharmaceutically acceptable salts as a solid spray-dried powder to treat opioid overdose.
Pharmacokinetics-based evaluation of nasal naloxone performance, including comparison to commercial naloxone nasal spray.
Ex vivo permeation evaluation using porcine nasal tissue.
Stability evaluation for naloxone and nalmefene using carrier-choice comparisons and impurity and chemical stability measurements.
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