METHODS AND FORMULATIONS FOR TOPICAL ADMINISTRATION OF GABAPENTINOIDS
The present disclosure is directed to novel ophthalmic formulations comprising a gabapentinoid and methods for treating corneal pain using said formulations.
1 . An ophthalmic formulation comprising a gabapentinoid present at a concentration of from about 0.1 to about 6.5 wt % and one or more pharmaceutically acceptable excipients, wherein the formulation has a viscosity of from about 1 to about 300 cPs and a pH from about 5 to about 8.
2 . The formulation of claim 1 , wherein the gabapentinoid is pregabalin or gabapentin.
3 . The formulation of claim 1 or 2 , wherein the concentration of the gabapentinoid is from about 0.1 wt % to about 5 wt %.
4 . The formulation of claim 3 , wherein the concentration of the gabapentinoid is from about 2 wt % to about 4 wt %.
5 . The formulation of claim 4 , wherein the concentration of the gabapentinoid is about 2 wt %.
6 . The formulation of claim 4 , wherein the concentration of the gabapentinoid is about 3 wt %. 7 The formulation of claim 4 , wherein the concentration of the gabapentinoid is about 4 wt %.
8 . The formulation of any one of claims 1 - 7 , wherein the viscosity is from about 5 to about 50 cPs.
9 . The formulation of any one of claims 1 - 8 , wherein the pH is from about 6.5 to about 7.5.
10 . The formulation of any one of claims 1 - 9 , wherein the formulation is an aqueous solution.
11 . The formulation of any one of claims 1 - 9 , wherein the formulation is a suspension.
12 . The formulation of any one of claims 1 - 9 , wherein the formulation is a semi-solid gel.
13 . The formulation of any one of claims 1 - 9 , wherein the formulation is an ointment.
14 . The formulation of any one of claims 1 - 13 , wherein the one or more pharmaceutically acceptable excipients are selected from the group consisting of preservatives, buffers, penetration enhancers, viscosity agents, tonicity regulators, chelating agents, polymers, lipids, ointment bases, and resuspension components, or combinations thereof.
15 . The formulation of any one of claims 1 - 14 , wherein the formulation further comprises an antimicrobial agent.
16 . The formulation of any one of claims 1 - 15 , wherein the osmolality of the formulation is from about 260 to about 365 mOsm/kg.
17 . The formulation of any one of claims 1 - 16 , wherein the formulation is isotonic.
18 . The formulation of any one of claims 1 - 16 , wherein the formulation is hypotonic.
19 . The formulation of any one of claims 1 - 16 , wherein the formulation is hypertonic.
20 . The formulation of any one of claims 1 - 19 , wherein the formulation is packaged in an aseptic manner.
21 . The formulation of any one of claims 1 - 20 , wherein the formulation is packaged in a single-dose container.
22 . The formulation of any one of claims 1 - 20 , wherein the formulation is packaged in a multiple-dose container.
23 . A method of treating corneal pain in a subject, comprising administering to the subject a therapeutically effective amount of the composition of any one of claims 1 - 22 .
24 . The method of claim 23 , wherein the corneal pain is acute corneal pain.
25 . The method of claim 23 , wherein the corneal pain is chronic corneal pain.
26 . The method of any one of claims 23 - 25 , wherein the subject is a human.
27 . The method of any one of claims 23 - 26 , wherein the composition is co-administered with a second pharmaceutical composition.
28 . The method of claim 27 , wherein the second pharmaceutical composition contains an active agent selected from the group consisting of non-steroidal anti-inflammatory drugs, local anesthetics, antimicrobial agents, immune suppressants, and steroids.
29 . The method of any one of claims 23 - 28 , wherein the ocular bioavailability of the gabapentinoid is improved by from about 5% to about 50% compared to oral administration of the same gabapentinoid.
30 . The method of any one of claims 23 - 29 , wherein the administering is into the cornea, the lower eyelid, an eye surface, or an ophthalmic tissue of at least one eye of the subject.
31 . The method of any one of claims 23 - 30 , wherein the administering is performed by intravitreal or intraocular injection.
32 . The method of any one of claims 23 - 31 , wherein the intensity of corneal pain in the subject decreases by from about 5 to about 50% as measured by an ocular pain questionnaire compared to treatment with oral administration of the same gabapentinoid or no treatment.
33 . The method of claim 32 , wherein the ocular pain questionnaire is selected from the group consisting of Ocular Pain Assessment Survey, visual analog scale (VAS), numerical rating scale (NRS), Wong-Baker FACES® Pain Rating Scale, and Eye Sensation Scale, or combination thereof.
34 . The method of any one of claims 23 - 33 , wherein the subject has reduced side effects compared to oral administration of the same gabapentinoid, wherein the side effects are selected from the group consisting of angioedema, hypersensitivity reactions, suicidal thoughts or behavior, respiratory depression, dizziness, somnolence, peripheral edema, blurred vision, weight gain, and difficulty with concentration and attention, or combinations thereof