EXTENDED-RELEASE PHARMACEUTICAL COMPOSITIONS FOR TREATING EYE CONDITIONS
The present disclosure encompasses methods and compositions for extended-release formulations for treating ophthalmic conditions. These formulations comprise a pharmaceutical agent, a cationic polymer, a non-ionic polymer, and a pharmaceutical carrier and are essentially preservative free. The formulations provided herein are particularly useful for sustained and controlled release of drugs and have low side effects.
1 . A sterile pharmaceutical composition for contacting an ocular surface of a mammal, the sterile pharmaceutical composition comprising:
a pharmaceutical agent,
a cationic polymer,
a non-ionic polymer, and
a pharmaceutical carrier,
wherein the duration of the clinical effect stemming from the sterile pharmaceutical composition is greater than 6 hours.
2 . (canceled)
3 . (canceled)
4 . The sterile pharmaceutical composition of claim 1 , further comprising one or more additional non-ionic polymers.
5 . The sterile pharmaceutical composition of claim 1 , further comprising an anionic polymer.
6 . (canceled)
7 . The sterile pharmaceutical composition of claim 5 , wherein the anionic polymer has a concentration of about 0.2% w/v to about 2.0% w/v.
8 . The sterile pharmaceutical composition of claim 1 , wherein the cationic polymer has a concentration of about 0.01% w/v to about 2.0% w/v.
9 . The sterile pharmaceutical composition of claim 1 , wherein the non-ionic polymer has a concentration of about 0.1% w/v to about 4.0% w/v.
10 . The sterile pharmaceutical composition of claim 1 , wherein the pharmaceutical carrier comprises one or more pharmaceutically acceptable buffers.
11 . (canceled)
12 . The sterile pharmaceutical composition of claim 1 , wherein the pharmaceutical carrier comprises one or more tonicity adjusting agents.
13 . (canceled)
14 . The sterile pharmaceutical composition of claim 1 , wherein the pharmaceutical carrier comprises one or more stabilizers.
15 . (canceled)
16 . The sterile pharmaceutical composition of claim 1 , wherein the pharmaceutical carrier comprises one or more pH adjusting agents.
17 . The sterile pharmaceutical composition of claim 1 , wherein the pharmaceutical carrier comprises water.
18 . The sterile pharmaceutical composition of claim 1 , wherein the pharmaceutical composition does not comprise a preservative.
19 . The sterile pharmaceutical composition of claim 1 , wherein the pharmaceutical composition has a viscosity of about 1 cP to about 20 cP.
20 . The sterile pharmaceutical composition of claim 1 , wherein the pharmaceutical composition has a pH of about 5.0 to about 8.0.
21 . (canceled)
22 . The sterile pharmaceutical composition of claim 1 , wherein the pharmaceutical agent comprises a cholinesterase inhibitor selected from the group consisting of any one of physostigmine, neostigmine, pyridostigmine, ambenonium, demecarium bromide, rivastigmine, galantamine, caffeine, rosmarinic acid, alpha-pinene, donepezil, tacrine, edrophonium, huperzine A, ladostigil, ungeremine, lactucopicrin, echothiophate, diisopropyl fluorophosphatesneostigmine, echothiophate iodide (also known as phospholine iodide), aceclidine, ambenonium, demecarium, rivastigmine, galantamine, acotiamide, diisopropyl fluorophsphate, cadusafos, chlorpyrifos, cyclosarin, dichlorvos, dimethoate, metrifonate, and any combination or pharmaceutically acceptable salts thereof.
23 . The sterile pharmaceutical composition of claim 22 , wherein the cholinesterase inhibitor has a concentration of about 0.001% w/v to about 0.1% w/v.
24 . (canceled)
25 . The sterile pharmaceutical composition of claim 1 , wherein the pharmaceutical agent comprises a muscarinic receptor agonist selected from the group consisting of pilocarpine, choline, acetylcholine, nicotine, methacholine, carbachol, cevimeline, CI-1017, bethanechol, milameline, muscarine, oxotremorine, sabcomeline, talsaclidine, tazomeline, vedaclidine, VU0152100, VU0238429, xenomeline, AF102B, AF150(S), AF267B, aceclidine, arecoline, pilocarpine, cevimeline, and any combination or pharmaceutically acceptable salts thereof.
26 . The sterile pharmaceutical composition of claim 25 , wherein the muscarinic agonist has a concentration of about 0.001% w/v to about 1% w/v.
27 . (canceled)
28 . The sterile pharmaceutical composition of claim 1 , wherein the pharmaceutical agent comprises a muscarinic receptor antagonist selected from the group consisting of atropine, scopolamine, glycopyrrolate, ipratropium bromide and any combination thereof or any pharmaceutically acceptable salt thereof.
29 . The sterile pharmaceutical composition of claim 28 , wherein the muscarinic receptor antagonist has a concentration of about 0.001% w/v to about 3% w/v.
30 . The pharmaceutical composition of claim 29 , wherein the pharmaceutical composition has a tropic acid concentration of less than 0.01 mg/ml after 180 days of storage in a sealed container at a temperature of 25° C. (±2) and 60% (±5%) relative humidity.
31 . The sterile pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is stable for at least 60 days, 120 days, or 180 days of storage in a sealed container at a temperature of 25° C. (±2) and 60% (±5%) relative humidity.
32 . (canceled)
33 . (canceled)
34 . (canceled)
35 . The sterile pharmaceutical composition of claim 1 , wherein the cationic polymer comprises chitosan.
36 . The sterile pharmaceutical composition of claim 1 , wherein the non-ionic polymer is selected from the group consisting of polyvinyl pyrrolidone (Povidine K30), a poly (oxyethylene-co-oxypropylene) block copolymer (Poloxamer 407), or a combination thereof.
37 . (canceled)
38 . The sterile pharmaceutical composition of claim 1 , wherein the pharmaceutical agent comprises an alpha-adrenergic agonist selected from the group consisting of phenoxybenzamine, phentolamine, tolazoline, trazodone, alfuzosin, dapiprazole, thymoxamine, doxazosin, prazosin, tamsulosin, bunezosin, terazosin, trimazosin, silodosin, atipamezole, idazoxan, mirtazapine, yohimbine, carvedilol, labetalol, urapidil, abanoquil, adimolol, ajmalicine, amosulalol, arotinolol, atiprosin, benoxathian, buflomedil, bunazosin, carvedilol, CI-926, corynanthine, DL-017, domesticine, eugenodilol, fenspiride, GYM-12743, GYKI-16084, indoramin, ketanserin, L-765314, mephendioxan, metazosin, monatepil, naftopidil, nantenine, neldazosin, nicergoline, niguldipine, pelanserin, phendioxan, piperoxan, quinazosin, ritanserin, RS-97078, SGB-1534, SL-890591, spiperone, talipexole, tibalosin, tiodazosin, tipentosin, tolazoline, upidosin, zolertine, a pharmaceutically acceptable salt thereof, and combinations thereof, and any combination or pharmaceutically-acceptable salts thereof.
39 - 95 . (canceled)