US2022071898A1PendingUtilityA1
Dipivefrin orally disintegrating tablet formulations
Est. expiryMar 1, 2039(~12.6 yrs left)· nominal 20-yr term from priority
Inventors:Mingbao Zhang
A61K 31/216A61K 9/0056A61K 9/2027A61K 9/006A61K 31/135A61K 9/2063A61K 9/2095A61K 31/222A61K 45/06A61K 31/137A61K 9/0019
62
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Claims
Abstract
This disclosure provides orally disintegrating dipivefrin tablet (ODT) formulations, including ODT formulations containing L-dipivefrin HCl. The ODT formulations of the disclosure include 10 to 70% binder (wt %), 5 to 50% matrix former (wt %), and 1 to 20% taste masking agent (wt %). The ODT formulations of the disclosure rapidly provide epinephrine to a patient when administered. The disclosure also provides a method of treating a patient who has a condition responsive to epinephrine such as a cardiac event, asthma, croup, cancer, a microbial infection, Addison's disease, or an allergic reaction, particularly anaphylaxis by administering an orally disintegrating dipivefrin tablet formulations to the patient.
Claims
exact text as granted — not AI-modified1 - 27 . (canceled)
28 . A method of treating a subject, suffering from a condition responsive to epinephrine comprising administering an orally disintegrating tablet (ODT), comprising dipivefrin, or a pharmaceutically acceptable salt thereof, a binder, a matrix former, and a taste masking agent to the subject, wherein the subject is a dog or human.
29 . The method of claim 28 , wherein the tablet produces no detectable epinephrine when dissolved in fresh human saliva at 37° C. for 3 minutes, as determined by HPLC.
30 . The method of claim 29 , wherein the amount of epinephrine is determined by HPLC, using the following conditions: C18 column, 3 μm, 100 mm×4.6 mm, temperature 30° C., 254 nm detection, 1.0 mL/minute flow rate, 10 microliter injection volume, elution gradient: Solvent A is 0.1% Trifluoroacetic acid (TFA) in H 2 O, Solvent B is 0.1% TFA in acetonitrile, and the gradient from 0 to 12 minutes is:
Time (min)
Solvent A (%)
Solvent B (%)
0
90
10
4
50
50
6
35
65
8
90
10
12
90
10
31 . The method of claim 28 , wherein the ODT comprises 0.01 mg to 20 mg dipivefrin hydrochloride.
32 . The method of claim 28 , wherein the ODT comprises 0.5 mg, 1.0 mg, 2.5 mg, or 5 mg dipivefrin hydrochloride.
33 . The method of claim 28 , wherein the condition responsive to epinephrine is a breathing difficulty.
34 . The method of claim 28 , wherein the condition responsive to epinephrine is anaphylaxis, asthma, bronchitis, emphysema, croup, or a respiratory infection.
35 . The method of claim 28 , wherein the condition responsive to epinephrine is anaphylaxis.
36 . The method of claim 28 wherein the condition responsive to epinephrine is Addison's disease, adrenal hyperplasia, hypoglycemia, or chronic active hepatitis.
37 . The method of claim 28 , wherein the condition responsive to epinephrine is a cancer.
38 . The method of claim 28 wherein the condition responsive to epinephrine is an autoimmune disorder.
39 . The method of claim 28 wherein the condition responsive to epinephrine is a microbial infection.
40 . The method of claim 28 wherein the condition response to epinephrine is cardiac arrest or superficial bleeding.
41 . A method of reducing the severity of an allergic reaction or anaphylaxis or inhibiting the onset of an allergic reaction or anaphylaxis in a subject, wherein the subject is a dog or human, and the method comprises administering an orally disintegrating tablet (ODT), comprising dipivefrin, or a pharmaceutically acceptable salt thereof, a binder, a matrix former, and a taste masking agent to the subject following exposure of the subject to an allergen.
42 . The method of claim 41 , additionally comprising administering an antihistamine to the subject.
43 . The method of claim 42 , wherein the antihistamine is diphenhydramine.
44 . A method of treating a subject, suffering from a condition responsive to epinephrine comprising administering an orally disintegrating tablet (ODT) to the subject, wherein the ODT comprises dipivefrin, or a pharmaceutically acceptable salt thereof, a binder, a matrix former, and a taste masking agent and the ODT produces not more than 13 percent epinephrine when dissolved in fresh human saliva at 37° C. for 11 minutes, as determined by HPLC.
45 . The method of claim 44 , wherein the percent epinephrine produced by the ODT is determined by HPLC, using the following conditions: C18 column, 3 μm, 100 mm×4.6 mm, temperature 30° C., 254 nm detection, 1.0 mL/minute flow rate, 10 microliter injection volume, elution gradient: Solvent A is 0.1% Trifluoroacetic acid (TFA) in H 2 O, Solvent B is 0.1% TFA in acetonitrile, and the gradient from 0 to 12 minutes is:
Time (min)
Solvent A (%)
Solvent B (%)
0
90
10
4
50
50
6
35
65
8
90
10
12
90
10
46 . The method of claim 45 , wherein the ODT comprises 0.01 mg to 20 mg dipivefrin hydrochloride.
47 . The method of claim 45 , wherein the ODT comprises 0.5 mg, 1.0 mg, 2.5 mg, or 5 mg dipivefrin hydrochloride, wherein the total weight of the tablet is less than 50 mg.
48 . The method of claim 45 , wherein the condition responsive to epinephrine is a breathing difficulty.
49 . The method of claim 45 , wherein the condition responsive to epinephrine is anaphylaxis, asthma, bronchitis, emphysema, croup, or a respiratory infection.
50 . The method of claim 45 , wherein the condition responsive to epinephrine is anaphylaxis.
51 . The method of claim 45 , wherein the condition responsive to epinephrine is cardiac arrest or superficial bleeding.
52 . A method of treating a subject, suffering from a condition responsive to epinephrine comprising administering a dipivefrin hydrochloride orally disintegrating tablet (ODT) to the subject, wherein the ODT comprises not more than 63.5 mg dipivefrin hydrochloride, a binder, a matrix former, and a taste masking agent, and the ODT provides an epinephrine T max of less than 45 minutes and a plasma epinephrine C max of 0.1 to 50 ng/mL, when administered to a dog or human.
53 . The method of claim 52 , wherein the condition responsive to epinephrine is anaphylaxis, asthma, bronchitis, emphysema, croup, or a respiratory infection.
54 . The method of claim 52 , wherein the condition responsive to epinephrine is anaphylaxis.
55 . The method of claim 52 , wherein the condition responsive to epinephrine is cardiac arrest or superficial bleeding.
56 . The method of claim 28 , wherein the dipivefrin is L-dipivefrin hydrochloride.
57 . The method of claim 53 , wherein the dipivefrin is L-dipivefrin hydrochloride.Join the waitlist — get patent alerts
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