Solid compositions for treating middle-of-the-night insomnia
The present invention provides compositions and methods for treating middle-of-the-night insomnia without residual sedative effects upon awakening by administering low doses (about 5 mg or less) of zolpidem or a salt thereof.
1 . A solid pharmaceutical composition for delivery across the oral mucosa for treating insomnia comprising zolpidem in an amount less than 5 mg and a buffer.
2 . A solid pharmaceutical composition of claim 1 , wherein the buffer comprises a carbonate buffer.
3 . A solid pharmaceutical composition of claim 1 , wherein the buffer comprises a bicarbonate buffer.
4 . A solid pharmaceutical composition of claim 1 , wherein the buffer comprises a carbonate buffer and a bicarbonate buffer.
5 . A solid pharmaceutical composition of claim 1 , wherein the buffer comprises a binary buffer.
6 . A solid pharmaceutical composition of claim 1 , wherein the amount of zolpidem is less than 1.30×10 −5 moles of zolpidem.
7 . A solid pharmaceutical composition of claim 1 , wherein the amount of zolpidem is about 1.5 to about 2.5 mg of zolpidem hemitartrate.
8 . A solid pharmaceutical composition of claim 1 , wherein the amount of zolpidem is about 3.0 to about 3.75 mg of zolpidem hemitartrate.
9 . A solid pharmaceutical composition of claim 1 , wherein the solid pharmaceutical composition is a sublingual tablet.
10 . A solid pharmaceutical composition of claim 1 , wherein the solid pharmaceutical composition is a lozenge.
11 . A solid pharmaceutical composition of claim 1 , wherein the zolpidem is delivered across at least one of the sublingual or buccal mucosa.
12 . A solid pharmaceutical composition for delivery across the oral mucosa for treating insomnia comprising zolpidem in an amount less than 5 mg and a binary buffer.
13 . A solid pharmaceutical composition of claim 12 , wherein the binary buffer comprises a carbonate buffer and a bicarbonate buffer.
14 . A solid pharmaceutical composition of claim 12 , wherein the amount of zolpidem is less than 1.30×10 −5 moles of zolpidem.
15 . A solid pharmaceutical composition of claim 12 , wherein the amount of zolpidem is about 1.5 to about 2.5 mg of zolpidem hemitartrate.
16 . A solid pharmaceutical composition of claim 12 , wherein the amount of zolpidem is about 3.0 to about 3.75 mg of zolpidem hemitartrate.
17 . A solid pharmaceutical composition of claim 12 , wherein the solid pharmaceutical composition is a sublingual tablet.
18 . A solid pharmaceutical composition of claim 12 , wherein the solid pharmaceutical composition is a lozenge.
19 . A solid unit dosage pharmaceutical composition comprising a dose of zolpidem hemitartrate in an amount of less than 5 mg and a binary buffer system capable of raising the pH of a subject's saliva to a pH greater than about 8.5, irrespective of the starting pH of saliva, wherein the composition is formulated for delivery of zolpidem across the subject's oral mucosa.
20 . A pharmaceutical composition of claim 19 , comprising from 1.5 to 2.5 mg of zolpidem hemitartrate.
21 . A pharmaceutical composition of claim 19 , comprising from 3.0 to 3.75 mg of zolpidem hemitartrate.
22 . A pharmaceutical composition of claim 21 , wherein said binary buffer system comprises sodium carbonate and sodium bicarbonate.
23 . A pharmaceutical composition of claim 21 , wherein said binary buffer system comprises a carbonate salt and a bicarbonate salt and said carbonate and bicarbonate are present in a carbonate:bicarbonate ratio of about 1:1.0 to about 1:1.2 by weight.
24 . A method of treating insomnia in a subject, said method comprising:
administering a solid pharmaceutical composition comprising zolpidem in an amount less than 5 mg and a buffer, to a subject who awakens from sleep and desires to resume sleep for less than 5 hours,
wherein the solid pharmaceutical composition provides delivery of zolpidem across the subject's oral mucosa, and wherein a blood level of zolpidem is achieved in the subject of between about 25 ng/ml and about 50 ng/ml within about 20 minutes of administration.
25 . A method in accordance with claim 24 , wherein the blood level of zolpidem in the subject is less than about 20 ng/ml at about 4 hours after administration.
26 . A method in accordance with claim 24 , wherein the solid pharmaceutical composition dissolves or disintegrates in the subject's mouth in about 2 minutes or less.
27 . A method in accordance with claim 24 , wherein the solid pharmaceutical composition dissolves or disintegrates in the subject's mouth in about 3 to about 6 minutes.
28 . A method in accordance with claim 24 , wherein the buffer is a binary buffer.
29 . A method in accordance with claim 28 , wherein the binary buffer comprises a carbonate buffer and a bicarbonate buffer.
30 . A method in accordance with claim 24 , wherein the buffer raises the pH of saliva in the subject's mouth to a pH greater than about 9.0.
31 . A method in accordance with claim 30 , wherein the pH of the saliva is raised above 9.0 for at least about 2 minutes.
32 . A method in accordance with claim 24 , wherein the zolpidem is delivered across at least one of the sublingual or buccal mucosa.
33 . A method of treating insomnia, said method comprising:
administering a solid pharmaceutical composition comprising zolpidem in an amount less than 5 mg and a binary buffer, to a subject who awakens from sleep and desires to resume sleep for less than 5 hours,
wherein the solid pharmaceutical composition provides delivery of zolpidem across the subject's oral mucosa, wherein the solid pharmaceutical composition dissolves or disintegrates in about 2 minutes or less in the subject's mouth, and wherein the binary buffer raises the pH of saliva in the subject's mouth to a pH greater than about 9.0.
34 . A method in accordance with claim 33 , wherein the pH of the saliva is raised above 9.0 for at least about 2 minutes.
35 . A method in accordance with claim 33 , wherein the binary buffer comprises a carbonate buffer and a bicarbonate buffer.
36 . A method in accordance with claim 33 , wherein a blood level of zolpidem in the subject is between about 25 ng/ml and about 50 ng/ml within about 20 minutes of administration.
37 . A method in accordance with claim 33 , wherein the blood level of zolpidem in the subject is less than about 20 ng/ml at about 4 hours after administration.
38 . A method in accordance with claim 33 , wherein the zolpidem is delivered across at least one of the sublingual or buccal mucosa.
39 . A method of treating insomnia, said method comprising the steps of:
providing a solid pharmaceutical composition comprising zolpidem in an amount less than 5 mg and a buffer to a patient who awakens from sleep and desires to resume sleep for less than 5 hours; and
administering the solid pharmaceutical composition to the patient for delivery of the zolpidem across the patient's oral mucosa,
wherein a blood level of zolpidem in the patient is between about 25 ng/ml and about 50 ng/ml within about 20 minutes of administration.
40 . A method in accordance with claim 39 , wherein the blood level of zolpidem in the patient is less than about 20 ng/ml at about 4 hours after administration.
41 . A method in accordance with claim 39 , wherein the solid pharmaceutical composition dissolves or disintegrates in the patient's mouth in about 2 minutes or less.
42 . A method in accordance with claim 39 , wherein the solid pharmaceutical composition dissolves or disintegrates in the patient's mouth in about 3 to about 6 minutes.
43 . A method in accordance with claim 39 , wherein the buffer is a binary buffer.
44 . A method in accordance with claim 43 , wherein the binary buffer comprises a carbonate buffer and a bicarbonate buffer.
45 . A method in accordance with claim 39 , wherein the buffer raises the pH of saliva in the patient's mouth to a pH greater than about 9.0.
46 . A method in accordance with claim 45 , wherein the pH of the saliva is raised above 9.0 for at least about 2 minutes.
47 . A method in accordance with claim 39 , wherein the zolpidem is delivered across at least one of the sublingual or buccal mucosa.
48 . A method of treating insomnia, said method comprising the steps of:
providing a solid pharmaceutical composition comprising zolpidem in an amount less than 5 mg and a binary buffer to a patient who awakens from sleep and desires to resume sleep for less than 5 hours; and
administering the solid pharmaceutical composition to the patient for delivery of the zolpidem across the patient's oral mucosa,
wherein the solid pharmaceutical composition dissolves or disintegrates in about 2 minutes or less in the patient's mouth and wherein the binary buffer raises the pH of saliva in the patient's mouth to a pH greater than about 9.0.
49 . A method in accordance with claim 48 , wherein the pH of the saliva is raised above 9.0 for at least about 2 minutes.
50 . A method in accordance with claim 48 , wherein the binary buffer comprises a carbonate buffer and a bicarbonate buffer.
51 . A method in accordance with claim 48 , wherein a blood level of zolpidem in the patient is between about 25 ng/ml and about 50 ng/ml within about 20 minutes of administration.
52 . A method in accordance with claim 48 , wherein the blood level of zolpidem in the patient is less than about 20 ng/ml at about 4 hours after administration.
53 . A method in accordance with claim 48 , wherein the zolpidem is delivered across at least one of the sublingual or buccal mucosa.
54 . A method in accordance with claim 48 , wherein the zolpidem is zolpidem hemitartrate.