US-20260124195-A1 - BUPROPION DOSAGE FORMS WITH REDUCED FOOD AND ALCOHOL DOSING EFFECTS

Abstract

This disclosure relates to dosage forms comprising bupropion hydrochloride, another salt form of bupropion, or the free base form of bupropion; dextromethorphan hydrobromide, another salt form of dextromethorphan, or the free base form of dextromethorphan, and a polymer. In some embodiments, the dosage form has no significant dose dumping of bupropion in the presence of ethanol in vitro. In some embodiments, the dosage form does not have a food effect for bupropion or dextromethorphan when taken with a high-fat meal in human subjects. Some embodiments include a method of treating a nervous system condition (such as depression, e.g., major depressive disorder, including treatment-resistant depression, agitation associated with Alzheimer's disease (or agitation associated with dementia of the Alzheimer's type), agitation associated with dementia, anxiety (or generalized anxiety disorder), neuropathic pain, or peripheral diabetic neuropathic pain) comprising, administering a dosage form described herein to a human being in need thereof.

Inventors

• Herriot Tabuteau

Assignees

• ANTECIP BIOVENTURES II LLC

Dates

Publication Date

20260507

Application Date

20251229

Claims (20)

1. 1 . A method of treating agitation associated with Alzheimer's disease in a human patient having agitation associated with Alzheimer's disease who is consuming alcohol, comprising: 1) administering a first dosage form once daily for one week to the human patient for the treatment of agitation associated with the patient's Alzheimer's disease, then administering the first dosage form twice daily to the human patient for one week; 2) then administering a second dosage form twice daily to the human patient for at least one week to treat the agitation associated with Alzheimer's disease; and 3) limiting alcohol consumption by the human patient; wherein the human patient consumes 4 servings of alcohol per week or less; wherein the first or second dosage form has no dose dumping of bupropion in the presence of ethanol in vitro; wherein the first dosage form comprises about 30 mg of dextromethorphan hydrobromide, or a molar equivalent amount of another salt form of dextromethorphan or the free base form of dextromethorphan, about 105 mg of bupropion hydrochloride, or a molar equivalent amount of another salt form of bupropion or the free base form of bupropion, and a polymer; wherein the second dosage form comprises about 45 mg of dextromethorphan hydrobromide, or a molar equivalent amount of another salt form of dextromethorphan or the free base form of dextromethorphan, and about 105 mg of bupropion hydrochloride, or a molar equivalent amount of another salt form of bupropion or the free base form of bupropion; and wherein the first or second dosage form is a two-layer dosage form, wherein the bupropion and the dextromethorphan are in separate layers.
2. 2 . The method of claim 1 , wherein the first or second dosage form further comprises colloidal silicon dioxide.
3. 3 . The method of claim 1 , wherein the first or second dosage form further comprises crospovidone.
4. 4 . The method of claim 1 , wherein the first or second dosage form further comprises: glyceryl monocaprylocaprate.
5. 5 . The method of claim 1 , wherein the first or second dosage form further comprises L-cysteine hydrochloride monohydrate.
6. 6 . The method of claim 1 , wherein the first or second dosage form further comprises magnesium stearate.
7. 7 . The method of claim 1 , wherein the first or second dosage form further comprises microcrystalline cellulose.
8. 8 . The method of claim 1 , wherein the first or second dosage form further comprises polyvinyl alcohol.
9. 9 . The method of claim 1 , wherein the first or second dosage form further comprises sodium lauryl sulfate.
10. 10 . The method of claim 1 , wherein the first or second dosage form further comprises stearic acid.
11. 11 . The method of claim 1 , wherein the first or second dosage form further comprises titanium dioxide.
12. 12 . The method of claim 1 , wherein the polymer is a carbomer homopolymer.
13. 13 . The method of claim 1 , wherein the first or second dosage form further comprises: colloidal silicon dioxide, crospovidone, glyceryl monocaprylocaprate, L-cysteine hydrochloride monohydrate, magnesium stearate, microcrystalline cellulose, polyvinyl alcohol, red iron oxide, sodium lauryl sulfate, stearic acid, talc, titanium dioxide, or yellow iron oxide, or a combination thereof.
14. 14 . The method of claim 1 , wherein the first or second dosage form comprises about 105 mg of bupropion hydrochloride.
15. 15 . The method of claim 1 , wherein the first dosage form comprises about 30 mg of dextromethorphan hydrobromide.
16. 16 . The method of claim 14 , wherein the first dosage form comprises about 30 mg of dextromethorphan hydrobromide.
17. 17 . The method of claim 1 , wherein the second dosage form comprises about 45 mg of dextromethorphan hydrobromide.
18. 18 . The method of claim 14 , wherein the second dosage form comprises about 45 mg of dextromethorphan hydrobromide.
19. 19 . The method of claim 1 , wherein the dextromethorphan is formulated for immediate release.
20. 20 . The method of claim 19 , wherein the bupropion is formulated for extended release.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS This application is a continuation of U.S. patent application Ser. No. 19/373,558, filed Oct. 29, 2025; which is a continuation of U.S. patent application Ser. No. 19/063,023, filed Feb. 25, 2025, now U.S. Pat. No. 12,472,174; which is a continuation of U.S. patent application Ser. No. 18/415,196, filed Jan. 17, 2024, now U.S. Pat. No. 12,263,161; which is a continuation of U.S. patent application Ser. No. 18/353,323, filed Jul. 17, 2023, now U.S. Pat. No. 11,925,636; which is a continuation of U.S. patent application Ser. No. 18/157,393, filed Jan. 20, 2023, now U.S. Pat. No. 11,717,518; which claims priority to U.S. Provisional Pat. App. No. 63/357,521, filed Jun. 30, 2022, U.S. Provisional Pat. App. No. 63/370,590, filed Aug. 5, 2022, and U.S. Provisional Pat. App. No. 63/370,771, filed Aug. 8, 2022; all of which are incorporated by reference herein in their entireties. FIELD This disclosure relates to dosage forms containing bupropion, optionally in the presence of dextromethorphan, and use of these dosage forms for various therapeutic purposes. SUMMARY This disclosure relates to dosage forms comprising bupropion hydrochloride, another salt form of bupropion, or the free base form of bupropion; dextromethorphan hydrobromide, another salt form of dextromethorphan, or the free base form of bupropion, and a polymer. In some embodiments, the dosage form has no significant dose dumping of bupropion in the presence of ethanol in vitro. In some embodiments, the dosage form does not have a food effect for bupropion when taken with a high-fat meal in human subjects. In some embodiments, the dosage form does not have a food effect for dextromethorphan when taken with a high-fat meal in human subjects. Some embodiments include a dosage form comprising: 105 mg of bupropion hydrochloride, or a molar equivalent amount of another salt form of bupropion or the free base form of bupropion, 45 mg of dextromethorphan hydrobromide, or a molar equivalent amount of another salt form of dextromethorphan or the free base form of dextromethorphan, and a polymer, wherein the dosage form, in the presence of ethanol in vitro, shows no significant dose dumping of bupropion. Some embodiments include a method of treating a nervous system condition (such as depression, e.g., major depressive disorder, including treatment-resistant depression, agitation associated with Alzheimer's disease (or agitation associated with dementia of the Alzheimer's type), agitation associated with dementia, anxiety (or generalized anxiety disorder), neuropathic pain, or peripheral diabetic neuropathic pain) comprising administering, once a day or twice a day, a dosage form to a human patient in need thereof, wherein the dosage form comprises 105 mg of bupropion hydrochloride, or a molar equivalent amount of another salt form of bupropion or the free base form of bupropion, 45 mg of dextromethorphan hydrobromide, or a molar equivalent amount of another salt form of dextromethorphan or the free base form of dextromethorphan, and a polymer, and wherein the dosage form, in the presence ethanol in vitro, shows no significant dose dumping of bupropion. Some embodiments include a method of treating a nervous system condition (such as depression, e.g., major depressive disorder, agitation associated with Alzheimer's disease (or agitation associated with dementia of the Alzheimer's type), agitation associated with dementia, anxiety (or generalized anxiety disorder), neuropathic pain, or peripheral diabetic neuropathic pain) comprising administering, once a day or twice a day, a dosage form to a human patient in need thereof, wherein the dosage form comprises 105 mg of bupropion hydrochloride, or a molar equivalent amount of another salt form of bupropion or the free base form of bupropion, 45 mg of dextromethorphan hydrobromide, or a molar equivalent amount of another salt form of dextromethorphan or the free base form of dextromethorphan, and a polymer, and wherein the patient consumes alcohol on a day that the dosage form is administered. Some embodiments include a method of treating a nervous system condition (such as depression, e.g., major depressive disorder, agitation associated with Alzheimer's disease (or agitation associated with dementia of the Alzheimer's type), agitation associated with dementia, anxiety (or generalized anxiety disorder), neuropathic pain, or peripheral diabetic neuropathic pain) in a human patient who is consuming alcohol, comprising administering, once a day or twice a day, a dosage form to a human patient in need thereof, and limiting but not discontinuing consumption of alcohol by the human patient, wherein the dosage form comprises 105 mg of bupropion hydrochloride, or a molar equivalent amount of another salt form of bupropion or the free base form of bupropion, 45 mg of dextromethorphan hydrobromide, or a molar equivalent amount of another salt form of dextromethorphan or the free base fo