PHARMACEUTICAL OPHTHALMIC COMPOSITIONS FOR INTRAOCULAR ADMINISTRATION AND METHODS FOR FABRICATING THEREOF
Pharmaceutical ophthalmic compositions are described, the compositions consisting essentially of a therapeutically effective quantity of an anti-bacterial agent (such as moxifloxacin), a therapeutically effective quantity of an anti-inflammatory agent (such as prednisolone), a combination of at least two solubilizing and suspending agents (of which one is a non-ionic polyoxyethlene-polyoxypropylene block copolymer), and a carrier. Methods for fabricating the compositions and using them are also described.
1 . A pharmaceutical composition formulated as a suspension that consists of:
(a) a dispersed phase consisting of solid particles consisting of a therapeutically effective quantity of a corticosteroid independently selected from the group consisting of triamcinolone, triamcinolone acetonide, triamcinolone diacetate, triamcinolone benetonide, triamcinolone furetonide, triamcinolone hexacetonide, betamethasone acetate, dexamethasone, fluorometholone, fluocinolone acetonide, and combinations thereof; and
(b) a dispersion medium consisting of:
(b1) a therapeutically effective quantity of at least one anti-bacterial agent independently selected from the group consisting of quinolone, a fluorinated quinolone and pharmaceutically acceptable salts, hydrates, solvates or N-oxides thereof;
(b2) a therapeutically effective quantity of an excipient consisting of at least one pharmaceutically acceptable solubilizing and suspending agent(s), with the further proviso that the excipient consists of:
(b2a) a first solubilizing and suspending agent selected from the group consisting of at least one non-ionic polyoxyethlene-polyoxypropylene block copolymer; and
(b2b) optionally, a second solubilizing and suspending agent selected from the group consisting of a water-soluble derivative of cellulose, optionally partially cross-linked polyacrylates, polyoxyethylene sorbitan monolaurates, polyoxyethylene sorbitan monopalmitates, polyoxyethylene sorbitan monostearates, polyoxyethylene sorbitan monooleates or combinations thereof;
(b3) optionally, a therapeutically effective quantity of at least one glycopeptide antibiotic selected from the group consisting of vancomycin, teicoplanin, telavancin, decaplanin, ramoplanin, gentamicin, tobramycin, amikacin, cefuroxime, polymyxin B sulfate, and trimethoprim;
(b4) optionally, a therapeutically effective quantity of at least one non-steroid anti-inflammatory drug selected from the group consisting of bromfenac, ketorolac, etodolac, sulindac, diclofenac, aceclofenac, nepafenac, tolmetin, indomethacin, nabumetone, ketoprofen, dexketoprofen, ibuprofen, flurbiprofen, dexibuprofen, fenoprofen, loxoprofen, oxaprozin, naproxen, aspirin, salicylic acid, diflunisal, salsalate, mefenamic acid, meclofenamic acid, flufenamic acid, tolfenamic acid, meloxicam, piroxicam, ternoxicam, droxicam, lornoxicam, isoxicam, celecoxib, rofecoxib, valdecoxib, parecoxib, lumiracoxib, etoricoxib, firocoxib, nimesulide, clonixin, licofelone, and pharmaceutically acceptable salts, hydrates, solvates, ethers, esters, acetals and ketals thereof; and
(b5) a pharmaceutically acceptable carrier,
wherein the dispersed phase is dispersed within the dispersion medium, with the further proviso that the pharmaceutical composition is an ophthalmic composition that is suitable for delivery via intraocular injection or via eye drops.
2 . The pharmaceutical composition of claim 1 , wherein the anti-bacterial agent is a fluorinated quinolone.
3 . The pharmaceutical composition of claim 2 , wherein the fluorinated quinolone is selected from the group consisting of moxifloxacin and gatifloxacin.
4 . The pharmaceutical composition of claim 3 , wherein the fluorinated quinolone is moxifloxacin.
5 . The pharmaceutical composition of claim 2 , wherein the fluorinated quinolone has the chemical structure (A):
6 . The pharmaceutical composition of claim 1 , wherein the corticosteroid is triamcinolone.
7 . The pharmaceutical composition of claim 1 , wherein:
(a) the anti-bacterial agent is moxifloxacin; and
(b) the corticosteroid is triamcinolone or a derivative thereof.
8 . The pharmaceutical composition of claim 1 , wherein the non-ionic polyoxyethlene-polyoxypropylene block copolymer is poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol).
9 . The pharmaceutical composition of claim 1 , wherein in the second solubilizing and suspending agent, if present, the water-soluble derivative of cellulose is selected from the group consisting of carboxymethyl cellulose, methyl cellulose, hydroxyethyl cellulose, and hydroxypropyl cellulose.
10 . The pharmaceutical composition of claim 1 , wherein the second solubilizing and suspending agent, if present, is polyoxyethylene (20) sorbitan monooleate.
11 . The pharmaceutical composition of claim 1 , wherein:
(a) the anti-bacterial agent is moxifloxacin at a concentration of about 1.0 mg/mL;
(b) the corticosteroid is triamcinolone acetonide at a concentration of about 15.0 mg/mL; and
(c) the non-ionic polyoxyethlene-polyoxypropylene block copolymer is at a concentration of about 1.0 mass %.
12 . The pharmaceutical composition of claim 1 , wherein the glycopeptide antibiotic, if present, is vancomycin.
13 . The pharmaceutical composition of claim 1 , wherein the non-steroid anti-inflammatory drug, if present, is bromfenac.
14 . A method for treating an ophthalmological disease, condition or pathology in a mammalian subject in need of such treatment comprising delivery to the subject the composition of claim 1 , wherein the method of delivery is selected from the group consisting of intravitreal injection, intraocular intracameral injection, intra-lesional injection, intra-articular injection, subconjunctival injection, sub-tenon injection, delivery via eye drops, delivery via spray and intra-canalicular delivery, to treat the ophthalmological disease, condition or pathology thereby.
15 . The method of claim 14 , wherein the intravitreal injection is selected from the group consisting of a transzonular injection and a non-transzonular injection.
16 . A method for treating an ophthalmological disease, condition or pathology in a mammalian subject in need of such treatment comprising intravitreally transzonularly injecting the subject with the composition of claim 1 , to treat the ophthalmological disease, condition or pathology thereby.
17 . A method for treating an ophthalmological disease, condition or pathology in a mammalian subject in need of such treatment comprising intraocularly injecting the subject with a composition of claim 1 , to treat the ophthalmological disease, condition or pathology thereby.
18 . A method for treating an ophthalmological disease, condition or pathology in a mammalian subject in need of such treatment comprising intravitreally transzonularly injecting the subject with the composition of claim 1 , to treat the ophthalmological disease, condition or pathology thereby.
19 . The method of claim 18 , wherein the injecting is intraoperative.
20 . A pharmaceutical kit, comprising a sealed container containing the pharmaceutical composition of claim 1 and an instruction for the use of the composition enclosed with the container.