Pharmaceutical composition for nasal delivery
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.
1. A solid pharmaceutical composition in the form of a spray-dried powder that is suitable for nasal delivery of naloxone or a pharmaceutically acceptable salt thereof, to treat opioid overdose, comprising:
a pharmacologically-effective amount of naloxone or a pharmaceutically acceptable salt thereof; and
a pharmaceutically-acceptable carrier material comprising a combination of:
(i) a disaccharide selected from the group consisting of maltitol, trehalose, sucralose, sucrose, isomalt, maltose, and lactose; and
(ii) a dextrin;
wherein the naloxone or pharmaceutically acceptable salt thereof is less than about 15% chemically degraded after 3 months at 75% relative humidity and 40° C.
2. A composition as claimed in claim 1 , wherein the powder has a particle size distribution that includes a d10 that is above about 3 μm.
3. A composition as claimed in claim 1 , wherein the disaccharide comprises lactose and/or trehalose.
4. A composition as claimed in claim 1 , wherein the dextrin comprises a cyclodextrin or a maltodextrin.
5. A composition as claimed in claim 1 , wherein the carrier material comprises α-D-lactose monohydrate as the lactose disaccharide and one or both of 2-hydroxypropyl-β-cyclodextrin and maltodextrin 12DE as the dextrin.
6. A composition as claimed in claim 1 , wherein the disaccharide is present in an amount of between about 10% and about 30% by weight based on the total weight of the composition.
7. A composition as claimed in claim 1 , wherein the dextrin is present in an amount of between 40% and about 80% by weight based on the total weight of the composition.
8. A composition as claimed in claim 1 , wherein the lowest measurable glass transition temperature of the composition is at least about 40° C. when measured at a relative humidity of up to about 35%.
9. A composition as claimed in claim 1 , wherein the powder has a particle size distribution that includes a volume-based mean diameter within the range of about 10 μm and about 100 μm.
10. A process for the manufacturing of a composition as defined in claim 1 , wherein said process comprises the steps of:
i) mixing together naloxone or salt thereof, the pharmaceutically-acceptable carrier materials in an appropriate volatile solvent; and
ii) spray-drying the mixture from step i) to form a spray-dried plurality of particles.
11. A composition obtainable by a process as defined in claim 10 .
12. A nasal applicator device suitable and/or adapted for delivery of a composition as defined in claim 1 to the nose, which comprises, or is adjunct and/or attached to, a reservoir, within which reservoir said composition is contained.
13. A process for the manufacturing of an applicator device as claimed in claim 12 , the process comprising:
i) mixing together naloxone or salt thereof and the pharmaceutically-acceptable carrier materials in an appropriate volatile solvent;
ii) spray-drying the mixture from step i) to form a spray-dried plurality of particles; and
iii) loading the composition formed in step ii) into the reservoir within or adjunct or attached to said applicator device.
14. A method of treating opioid overdose, which method comprises administering a composition as defined in claim 1 to a subject in need of such treatment.
15. A method as claimed in claim 14 , wherein the composition is administered to said subject by way of an applicator that comprises or is adjunct and/or attached to, a reservoir, within which reservoir said composition is contained.