Pharmaceutical composition for drug delivery
According to the invention, there is provided a pharmaceutically-acceptable composition which is preferably in the form of a spray-dried powder comprising a mixture of: (a) a pharmacologically-effective dosage amount of at least one pharmaceutically-active compound; and (b) a pharmaceutically-acceptable carrier material, which carrier material comprises a combination of a disaccharide and a polymeric material. Compositions are suitable for, for example, transmucosal drug delivery, including sublingual and nasal delivery. In the case of nasal delivery, said compositions may be loaded into single- or multiple-use nasal applicators. Preferred pharmaceutically-acceptable carriers in this regard include lactose or trehalose and dextrins (e.g. cyclodextrins or maltodextrins), which may be spray-dried together in combination. Compositions may further comprise one or more alkyl saccharides. Preferred alkyl saccharides include sucrose esters, such as sucrose monolaurate.
1. A nasal applicator device for intranasal delivery of a composition to nasal mucosa, wherein the device comprises a reservoir containing a composition in the form of an amorphous powder and being free of liquid propellant,
wherein said amorphous powder comprises
(a) a pharmacologically-effective dosage amount of epinephrine or a pharmaceutically-acceptable salt thereof as sole active ingredient; and
(b) a pharmaceutically-acceptable carrier material, which carrier material comprises a combination of a disaccharide and a polymeric material comprising a dextrin and/or hydroxypropylmethyl cellulose;
wherein the particles of the amorphous powder comprise an amorphous composite of epinephrine or salt thereof and the carrier material; and
wherein the nasal applicator device is configured and the particles are of a size whereby said device, upon actuation, is capable of depositing an effective dose of epinephrine, or salt thereof, to the nasal mucosa.
2. The nasal applicator device as claimed in claim 1 wherein said amorphous powder is a dry, amorphous powder.
3. The nasal applicator device as claimed in claim 1 , wherein the nasal applicator device is a single-use device and the reservoir contains a single dose of said amorphous powder.
4. The nasal applicator device as claimed in claim 1 , wherein the particles of said amorphous powder have a D10 above about 10 um.
5. The nasal applicator device as claimed in claim 4 , wherein the particles of said amorphous powder have a D90 below about 500 um.
6. The nasal applicator device as claimed in claim 4 , wherein the particles of said amorphous powder have a D90 below about 100 um.
7. The nasal applicator device as claimed in claim 1 , wherein the carrier material comprises a combination of:
(i) lactose or trehalose, and
(ii) a maltodextrin; and
the amorphous powder composition further comprises sucrose monolaurate.
8. The nasal applicator device as claimed in claim 1 , wherein the disaccharide is selected from the group consisting of maltitol, trehalose, sucralose, sucrose, isomalt, maltose and lactose.
9. The nasal applicator device as claimed in claim 8 , wherein the disaccharide comprises lactose or trehalose.
10. The nasal applicator device as claimed in claim 1 , wherein the dextrin comprises a cyclodextrin or a maltodextrin.
11. The nasal applicator device as claimed in claim 1 , wherein the carrier material comprises a combination of:
(i) lactose or trehalose; and
(ii) a maltodextrin.
12. The nasal applicator device as claimed in claim 1 , wherein the ratio of disaccharide:polymeric material by weight, based on the total weight of the composition, is in the range of about 10:1 and about 1:20.
13. The nasal applicator device as claimed in claim 12 , wherein the ratio of disaccharide:polymeric material by weight, based on the total weight of the composition, is in the range of about 2:1 to about 1:8.
14. The nasal applicator device 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%.
15. The nasal applicator device as claimed in claim 1 , wherein the composition further comprises a sucrose ester.
16. The nasal applicator device as claimed in claim 15 , wherein the sucrose ester comprises sucrose monolaurate.
17. The nasal applicator device as claimed in claim 1 , wherein the pharmacologically-effective dosage amount of epinephrine is between about 0.1 mg and about 5 mg (calculated as the free base compound).
18. The nasal applicator device as claimed in claim 1 , wherein the particle size distribution includes a D10 that is above about 3 μm.
19. The nasal applicator device 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.
20. A process for the manufacturing of the applicator device as claimed in claim 1 , which comprises loading said amorphous powder into the reservoir of said applicator device.
21. The process as claimed in claim 20 , wherein said amorphous powder loaded into the reservoir is a dry, amorphous powder.