Claims for Patent: 10,792,253

Summary for Patent: 10,792,253

Title:	Pharmaceutical compositions
Abstract:	Disclosed herein are pharmaceutical powder compositions, methods of making such compositions, and uses thereof.
Inventor(s):	Shunji Haruta
Assignee:	Shin Nippon Biomedical Laboratories Ltd
Application Number:	US15/668,871
Patent Claims:	1. An intranasal pharmaceutical powder composition, wherein the intranasal pharmaceutical powder composition comprises particles that comprise an active agent, a carrier, and at least one member selected from the group consisting of a thickening agent, a pH adjusting agent, a sugar alcohol, and any combination thereof, and wherein: the active agent comprises dihydroergotamine (DHE) or a pharmaceutically acceptable salt thereof, indomethacin or a pharmaceutically acceptable salt thereof, or testosterone or a pharmaceutically acceptable salt thereof; the carrier comprises a microcrystalline cellulose, wherein the microcrystalline cellulose is at least partially coated with the active agent; at least about 20 percent by weight of the active agent in the particles is amorphous as determined by X-ray diffraction; when the active agent has a crystalline form, a solubility of the active agent in a crystalline form in an aqueous liquid ranges from about 0.1 μg/mL to about 1 mg/mL in water at a temperature of 37±0.5° C.; the particles have an average particle size of about 10 microns to about 300 microns, as measured by laser diffraction; and when the intranasal pharmaceutical powder composition is administered to a human subject, a pharmacokinetic parameter of the active agent increases by at least about 15%, compared to a corresponding composition that comprises the active agent that is in a crystalline form when administered intranasally to a comparable human subject, as measured by a same method, and wherein the pharmacokinetic parameter comprises AUC0-10min, AUC0-15min, AUC0-30min, Cmax, or any combination thereof. 2. The intranasal pharmaceutical powder composition of claim 1, wherein: the intranasal pharmaceutical powder composition further comprises particles at least some of which substantially contain a single ingredient selected from the group consisting of the active agent, the thickening agent, the carrier, the pH adjusting agent, and the sugar alcohol; or the intranasal pharmaceutical powder composition further comprises particles at least some of which contain a single ingredient selected from the group consisting of the active agent, the thickening agent, the carrier, the pH adjusting agent, and the sugar alcohol; or the intranasal pharmaceutical powder composition further comprises particles at least some of which contain at least two ingredients selected from the group consisting of the active agent, the thickening agent, the carrier, the pH adjusting agent, and the sugar alcohol; or the intranasal pharmaceutical powder composition further comprises particles that comprise the active agent and are free from the thickening agent, the carrier, or a combination thereof; or at least some of the particles are aggregates; or at least some of the particles are agglomerates; or any combination thereof. 3. The intranasal pharmaceutical powder composition of claim 1, wherein the active agent is dihydroergotamine (DHE) or a pharmaceutically acceptable salt thereof. 4. The intranasal pharmaceutical powder composition of claim 3, wherein the active agent is DHE mesylate. 5. The intranasal pharmaceutical powder composition of claim 1, wherein the active agent is indomethacin or a pharmaceutically acceptable salt thereof. 6. The intranasal pharmaceutical powder composition of claim 1, wherein the active agent is testosterone or a pharmaceutically acceptable salt thereof. 7. The intranasal pharmaceutical powder composition of claim 1, wherein the carrier further comprises ethyl cellulose, cellulose acetate, cellulose acetate butyrate, cellulose acetate propionate, cellulose acetate phthalate, hydroxypropylmethylcellulose phthalate, starch, chitosan, or any combination thereof. 8. The intranasal pharmaceutical powder composition of claim 1, wherein the microcrystalline cellulose has an average particle size of about 20 μm to about 50 μm. 9. The intranasal pharmaceutical powder composition of claim 1, wherein the sugar alcohol is selected from the group consisting of mannitol, glycerol, galactitol, fucitol, inositol, volemitol, maltotriitol, maltoetetraitol, polyglycitol, erythritol, threitol, ribitol, arabitol, xylitol, allitol, dulcitol, glucitol, sorbitol, altritol, iditol, maltitol, lactitol, isomalt, and any combination thereof. 10. The intranasal pharmaceutical powder composition of claim 1, wherein the intranasal pharmaceutical powder composition comprises the active agent, the carrier that is microcrystalline cellulose, and the sugar alcohol that is mannitol. 11. The intranasal pharmaceutical powder composition of claim 1, wherein the intranasal pharmaceutical powder composition comprises the active agent that is dihydroergotamine or a pharmaceutically acceptable salt thereof, the carrier that is microcrystalline cellulose, and the sugar alcohol that is mannitol. 12. The intranasal pharmaceutical powder composition of claim 11, wherein the intranasal pharmaceutical powder composition further comprises the thickening agent that is hydroxypropyl methylcellulose (HPMC). 13. The intranasal pharmaceutical powder composition of claim 11, wherein the intranasal pharmaceutical powder composition comprises: 1) the dihydroergotamine or a pharmaceutically acceptable salt thereof that is present in about 20% of a total weight of the intranasal pharmaceutical powder composition; 2) the mannitol that is present in about 25% of the total weight of the intranasal pharmaceutical powder composition; and 3) the microcrystalline cellulose that is present in about 55% of the total weight of the intranasal pharmaceutical powder composition, and wherein the intranasal pharmaceutical powder composition has an average particle size diameter of about 20 to about 100 μm. 14. The intranasal pharmaceutical powder composition of claim 1, wherein the intranasal pharmaceutical powder composition comprises: 1) about 1 to about 8 mg of the dihydroergotamine or a pharmaceutically acceptable salt thereof; 2) about 5 to about 15 mg of the mannitol; and 3) about 5 to about 15 mg of the microcrystalline cellulose. 15. The intranasal pharmaceutical powder composition of claim 14, wherein the intranasal pharmaceutical powder composition comprises: 1) about 4 mg of the dihydroergotamine or a pharmaceutically acceptable salt thereof; 2) about 5 mg of the mannitol; and 3) about 11 mg of the microcrystalline cellulose, and wherein the intranasal pharmaceutical powder composition has an average particle size diameter of about 20 to about 100 μm. 16. The intranasal pharmaceutical powder composition of claim 1, wherein the intranasal pharmaceutical powder composition comprises the active agent that is indomethacin or a pharmaceutically acceptable salt thereof and the carrier that is microcrystalline cellulose, and further comprises tribasic calcium phosphate. 17. The intranasal pharmaceutical powder composition of claim 1, wherein the intranasal pharmaceutical powder composition comprises the active agent that is testosterone or a pharmaceutically acceptable salt thereof and the carrier that is microcrystalline cellulose, and further comprises tribasic calcium phosphate. 18. A method, comprising intranasally administering to a subject the intranasal pharmaceutical powder composition of claim 1. 19. The intranasal pharmaceutical powder composition of claim 11, wherein the intranasal pharmaceutical powder composition comprises: 1) about 1 to about 8 mg of the dihydroergotamine or a pharmaceutically acceptable salt thereof; 2) about 5 to about 15 mg of the mannitol; 3) about 5 to about 15 mg of the microcrystalline cellulose; and 4) the thickening agent that is hydroxypropyl methyl cellulose (HPMC). 20. The intranasal pharmaceutical powder composition of claim 12, wherein the intranasal pharmaceutical powder composition comprises: 1) the dihydroergotamine or a pharmaceutically acceptable salt thereof that is present in about 1% to about 30% of a total weight of the intranasal pharmaceutical powder composition; 2) the mannitol that is present in about 15% to about 55% of the total weight of the intranasal pharmaceutical powder composition; 3) the microcrystalline cellulose that is present in about 40% to about 75% of the total weight of the intranasal pharmaceutical powder composition, and 4) the hydroxypropyl methylcellulose (HPMC) that is present in about 0.05% to about 5% of the total weight of the intranasal pharmaceutical powder composition.