WO2013065029A1 - Fixed dose combination containing moxifloxacin and prednisolone for treatment of ocular infections - Google Patents

Fixed dose combination containing moxifloxacin and prednisolone for treatment of ocular infections Download PDF

Info

Publication number
WO2013065029A1
WO2013065029A1 PCT/IB2012/056151 IB2012056151W WO2013065029A1 WO 2013065029 A1 WO2013065029 A1 WO 2013065029A1 IB 2012056151 W IB2012056151 W IB 2012056151W WO 2013065029 A1 WO2013065029 A1 WO 2013065029A1
Authority
WO
WIPO (PCT)
Prior art keywords
composition
pharmaceutically acceptable
prednisolone
moxifloxacin
effective amount
Prior art date
Application number
PCT/IB2012/056151
Other languages
French (fr)
Inventor
Rajesh Kshirsagar
Shivanand Dhanure
Sachin Mundade
Original Assignee
Micro Labs Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to IN2666/CHE/2011 priority Critical
Priority to IN2666CH2011 priority
Application filed by Micro Labs Limited filed Critical Micro Labs Limited
Publication of WO2013065029A1 publication Critical patent/WO2013065029A1/en

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/56Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives, e.g. steroids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0048Eye, e.g. artificial tears

Abstract

The present invention relates to use of a fixed dose combination comprising an effective amount of Moxifloxacin or its pharmaceutically acceptable salts thereof and an effective amount of Prednisolone or its pharmaceutically acceptable esters or salts thereof for the treatment of ocular infections. The present invention further relates to a pharmaceutical composition comprising fixed dose combination comprising an effective amount of Moxifloxacin or its pharmaceutically acceptable salts thereof and an effective amount of Prednisolone or its pharmaceutically acceptable esters or salts thereof for the treatment of ocular infections.

Description

FIXED DOSE COMBINATION CONTAINING MOXIFLOXACIN AND PREDNISOLONE FOR TREATMENT OF OCULAR INFECTIONS

FIELD OF THE INVENTION:

The present invention relates to a fixed dose combination comprising one or more antibiotics and one or more steroidal anti-inflammatory agents for the treatment of ocular infections.

BACKGROUND OF THE INVENTION

Eye is susceptible to bacterial and parasitic infections arising from both traumatic and non-traumatic related events. Infections are a concern after ocular surgery, and precautions are correspondingly taken to prevent the onset of infection. However, even without the invasive trauma of a surgical procedure, infections in the eyelids, conjunctiva, cornea, and other ocular tissues can occur.

The causes of ocular infections generally come from one of two different sources: the eyelids or the sinuses. The most common reasons why the eyes get infected are through surgery, trauma, low immunity, and improper contact care.

The treatment of choice for treating ocular infections includes antibiotics and steroidal anti-inflammatory agents.

However literature survey revealed that nobody till date has used fixed dose combination containing antibiotic and steroidal anti-inflammatory agent for the treatment of ocular infections.

The present inventors have found that a fixed dose combination comprising one or more antibiotics and one or more steroidal anti-inflammatory agents are effective treatment of ocular infections.

SUMMARY OF THE INVENTION

The present invention is directed to a method of treating ocular infections, comprising administration of a fixed dose combination comprising one or more antibiotics and one or more steroidal anti-inflammatory agents.

In one aspect, the present invention provides a fixed dose combination comprising one or more antibiotics and one or more steroidal anti-inflammatory agents for the treatment of ocular infections. In yet another aspect, the present invention provides a pharmaceutical composition comprising a fixed dose combination comprising one or more antibiotics and one or more steroidal anti-inflammatory agents.

In yet another aspect, the present invention provides a process for preparation of a pharmaceutical composition comprising a fixed dose combination comprising one or more antibiotics and one or more steroidal anti-inflammatory agents for the treatment of ocular infections.

In yet another aspect, the present invention provides a method of treating an ocular infections, comprising administering to an affected eye of patient a combination of an effective amount of Moxifloxacin or its pharmaceutically acceptable salts thereof and an effective amount of Prednisolone or its pharmaceutically acceptable esters or salts thereof optionally together with pharmaceutically acceptable excipients.

In one aspect, the present invention provides a fixed dose combination comprising an effective amount of Moxifloxacin or its pharmaceutically acceptable salts thereof and an effective amount of Prednisolone or its pharmaceutically acceptable esters or salts thereof for the treatment of ocular infections.

In yet another aspect, the present invention provides a pharmaceutical composition comprising a fixed dose combination comprising an effective amount of Moxifloxacin or its pharmaceutically acceptable salts thereof and an effective amount of Prednisolone or its pharmaceutically acceptable esters or salts thereof for the treatment of ocular infections.

In yet another aspect, the present invention provides a process for preparation of a pharmaceutical composition comprising a fixed dose combination comprising an effective amount of Moxifloxacin or its pharmaceutically acceptable salts thereof and an effective amount of Prednisolone or its pharmaceutically acceptable esters or salts thereof for the treatment of ocular infections.

DETAILED DESCRIPTION OF INVENTION

The invention includes the combinational use of one or more and antibiotics one or more anti-inflammatory steroids for the treatment of ocular infections. More specifically, the present invention includes a combinational use of an effective amount of Moxifloxacin or its pharmaceutically acceptable salts thereof and an effective amount of Prednisolone or its pharmaceutically acceptable esters or salts thereof for the treatment of ocular infections.

As used herein, the term "ocular infections" refers to infections which are caused by viruses and bacteria entering the eye. While the eyes are constantly exposed to a variety of germs, bacteria, and viruses, sometimes the body's defenses fail and an eye infection can result. Eye infections are most commonly spread by hand-to-eye contact, infections traveling from the sinuses, or through poor eye hygiene (especially contact-lens hygiene). Other causes include complications from eye surgery, eye trauma, immune deficiency, or other eye problems or illness that result in bacteria or viral growth. Systemic overgrowth of the fungus Candida albicans known as Candidiasis can also cause recurrent eye infections and eye pain. Ocular infections can be conjunctivitis, ophthalmic neonatorum, trachoma, corneal ulcers, keratitis, keratoconjunctivitis, endophthalmitis, infectious uveitis and combinations thereof.

As used herein, the term "antibiotics" refers to drugs which are produced by micro-organism in nature and isolated from this natural source or synthesized by chemical process which can kill harmful microorganism and cure bacterial infections in human and animals.

As used herein, the term "anti-inflammatory steroids" refers to the drugs that block the synthesis of new histamine release by mast cells, inactivate available histamine, inhibit mast cell degranulation, decrease capillary permeability, and inhibit phospholipase A synthesis, which is used in the production of arachidonic acid and thereby prevent inflammation.

In one advantageous embodiment, the active components of present invention are present in the form of a fixed dose combination, owing to which the administration is simpler for the patients, since both active compounds are contained in one and the same container.

In one embodiments, the compositions and formulations described herein comprise a first active agent and a second active agent, wherein the first active agent and the second active agent are formulated into the composition or formulation in a manner that allows ophthalmic and/or topical activity of the agents (e.g., by formulating a composition or formulation described herein as a solution, gel, or the like, comprising a first active agent and a second active agent as solutes within the solution, gel, suspension etc.). It is to be understood that such compositions and formulations include compositions and formulations wherein a substantial portion, a therapeutically effective portion, most or all of the first and second agents are either dissolved or suspended in the liquid medium (e.g., aqueous medium) based on their solubility in liquid medium.

In specific embodiment, the present invention provides a fixed dose combination of Moxifloxacin or its pharmaceutically acceptable salts thereof and Prednisolone or its pharmaceutically acceptable esters or salts thereof.

In yet another embodiment, the antibiotics (e.g. Moxifloxacin or its pharmaceutically acceptable salts thereof) are present in a composition or formulation described herein in an amount of about 0.05 wt % to about 5 wt %, preferably about 0.1 wt % to about 1 wt % , more preferably 0.5 wt %.

In yet another embodiment, the anti-inflammatory steroids (e.g. Prednisolone or its pharmaceutically acceptable esters or salts thereof) are present in a composition or formulation described herein in an amount of about 0.1 wt % to about 10 wt %, preferably about 0.5 wt % to about 5 wt % , more preferably 1 wt % to 2 wt %.

In yet other embodiment, the ophthalmic composition of present invention have a pH from 4.0 to 8.0, preferably from 4.5 to 7.5, more preferably from 5.0 to 7.0.

In yet another embodiment, the ophthalmic composition of present invention has an osmolarity from 200 to 400 milliosmoles/liter (mOsm/L), preferably from 250 to 375 mOsm/L, and more preferably from 270 to 330 mOsm/L.

In yet another embodiment, the compositions, formulations and active pharmaceutical agent described herein are thermally stable at room temperature, at 25° C with relative humidity 40% or at 40 °C with relative humidity NMT 25% for at least 3 months.

Examples of antibiotics include, but are not limited to, Aminoglycosides such as; Amikacin, Gentamycin, Kanamycin, Neomycin, Netilmicin, Paromomycin, Streptomycin, Tobramycin, Carbapenems such as; Ertapenem, Imipenem, Meropenem, Chloramphenicol, Fluoroquinolones such as; Ciprofloxacin, Gatifloxacin, Gemifloxacin, Grepafloxacin, Levofloxacin, Besifloxacin, Lomefloxacin, Moxifloxacin, Norfloxacin, Ofloxacin, Sparfloxacin, Trovafloxacin, Glycopeptides such as; Vancomycin, Lincosamides such as; Clindamycin, Macrolides/Ketolides such as; Azithromycin, Clarithromycin, Dirithromycin, Erythromycin, Telithromycin, Cephalosporins such as; 1st Generation - Cefadroxil, Cefazolin, Cephalexin, Cephalothin, Cephapirin, Cephradine, 2nd Generation - Cefaclor, Cefamandole, Cefonicid, Cefotetan, Cefoxitin, Cefprozil, Cefuroxime, Loracarbef, 3rd Generation - Cefdinir, Cefditoren, Cefixime, Cefoperazone, Cefotaxime, Cefpodoxime,Ceftazidime, Ceftibuten, Ceftizoxime, Ceftriaxone, 4th Generation - Cefepime, Monobactams such as; Aztreonam, Nitroimidazoles such as; Metronidazole, Oxazolidinones such as Linezolid, Penicillins such as Amoxicillin, Amoxicillin/Clavulanate, Ampicillin, Ampicillin/Sulbactam, Bacampicillin, Carbenicillin, Cloxacillin, Dicloxacillin, Methicillin, Mezlocillin, Nafcillin, Oxacillin, Penicillin G, Penicillin V, Piperacillin, Piperacillin/Tazobactam, Ticarcillin, Ticarcillin/Clavulanate, Streptogramins such as; Quinupristin/Dalfopristin, Tetracyclines such as; Demeclocycline, Doxycycline, Minocycline, Tetracycline or its physiologically acceptable salts thereof, prodrugs thereof, combinations thereof, mixtures thereof and the like.

Examples of steroidal anti-inflammatory agents according to the present invention include, but are not limited to, Prednisolone , sulfacetamide, Hydrocortisone , Difluprednate, Fluorometholone acetate, Dexamethasone, Prednisolone phosphate , Rimexolone, 21-acetoxypregnenolone, alclometasone, algestone, amcinonide, beclomethasone, betamethasone, budesonide, chloroprednisone, clobetasol, clobetasone, clocortolone, cloprednol, corticosterone, cortisone, cortivazol, deflazacort, desonide, desoximetasone, diflorasone, diflucortolone, enoxolone, fluazacort, flucloronide, flumethasone, flunisolide, fluocinolone acetonide, fluocinonide, fluocortin butyl, fluocortolone, fluperolone acetate, fluprednidene acetate, fluprednisolone, flurandrenolide, fluticasone propionate, formocortal, halcinonide, halobetasol propionate, halometasone, halopredone acetate, hydrocortarnate, loteprednol etabonate, mazipredone, medrysone, meprednisone, methylprednisolone, mometasone furoate, paramethasone, prednicarbate, prednisolone 25-diethylamino-acetate, prednisolone sodium phosphate, prednisone, prednival, prednylidene, tixocortol, triamcinolone, triamcinolone acetonide, triamcinolone benetonide, triamcinolone hexacetonide, prednisone, methylprednisolone, medrysone, triamcinolone or its physiologically acceptable esters thereof, salts thereof, prodrugs thereof, combinations thereof, mixtures thereof and the like.

A pharmaceutical composition according to the present invention may include one or more pharmaceutically acceptable buffering agents, preservatives, tonicity- adjusting agents, antioxidants, pH-adjusting agents, chelating agents, viscosity modifiers, wetting agents, solubilizing agents.

Examples of buffering agents include, but are not limited to, phosphate buffer such as dibasic sodium phosphate heptahydrate, monobasic sodium phosphate monohydrate; and/or borate buffer such as sodium borate, boric acid; and/or citrate buffer, acetate buffer; carbonate buffer; borate -polyol complexes, and the like

Examples of preservatives include, but are not limited to, benzalkonium chloride, benzethonium chloride, p- oxybenzoates such as methyl p-oxybenzoate or ethyl p- oxybenzoate, benzyl alcohol, phenethyl alcohol, sorbic acid or its salt, thimerosal, chlorobutanol, other quaternary amines and the like, chlorhexidine gluconate and the like.

Examples of tonicity-adjusting agents include, but are not limited to, mannitol, sodium chloride, xylitol, and the like.

Examples of antioxidants include, but are not limited to, ascorbic acid, malic acid, citric acid, sodium citrate, butylated hydroxyanisole, butylated hydroxytoluene, propyl gallate, sodium ascorbate, sodium metabisulfite and the like and mixtures thereof.

Examples of the alkaline agents that may be used as pH adjusting agents, include, but are not limited to, sodium hydroxide (NaOH), potassium hydroxide (KOH), tromethamine, monoethanolamine, sodium bicarbonate (NaHC03) and other organic and inorganic bases.

Examples of the acidic agents that may be used as pH adjusting agents include, but are not limited to, hydrochloric acid, citric acid, tartaric acid, lactic acid and other organic and inorganic acids and the like and mixtures thereof.

Examples of chelating agents include, but are not limited to, EDTA, disodium edetate, sodium citrate, condensed sodium phosphate and the like Examples of viscosity modifiers include, but are not limited to, hydroxypropylmethyl cellulose (hypromellose), carboxypropylmethylcellulose, polyvinylpyrrolidone (Povidone), polyethylene glycol, polyvinyl acetate, and combinations thereof.

Examples of wetting agents include, but are not limited to, cetylpyridinium chloride, tyloxapol, and various polysorbates such as Tween® which includes Tween 80, polyethoxylated substances and poloxamers.

Examples of solubilizing agents include, but are not limited to, cyclodextrins (CDs) such as Hydroxypropyl beta-CD, hydroxypropyl gamma-CD (Cavasol®), sulfobutyl ether4 beta-CD (Captisol®), and hydroxypropyl beta-CD (Kleptose®).

EXAMPLES

The invention will be further illustrated by the following examples, which are intended to be illustrative but not limiting.

Example No. 1

Table No. 1: Ophthalmic Suspension containing Moxifloxacin Hydrochloride Eq. to Moxifloxacin (0.5% w/v dissolved) & Prednisolone acetate (1.0% w/v suspended)

Sr. No. Name of Pharmaceutical Ingredient Quantity (mg/ml)

1 Moxifloxacin Hydrochloride 5.45

2 Prednisolone acetate 10.0

3 Benzalkonium Chloride 0.1

4 Polysorbate 80 1.0

5 Disodium edetate 0.10

6 Hypromellose 1.0

7 Hydroxypropyl betacyclodextrin 5.0

8 Sodium metabisulfite 1.0

9 Sodium chloride 3.0

10 Boric acid 10.0 11 Sodium Hydroxide/Hydrochloric acid q.s

12 Water for injections q.s to 1 mL

Manufacturing process:

A formulation as shown in table 1 was prepared as follows:

(a) Accurately weighed quantity of Moxifloxacin Hydrochloride and required quantity of Hydroxypropyl betacyclodextrin, Disodium edetate, Sodium metabisulfite,

Polysorbate 80 were introduced into suitable container and dissolved it in sufficient water for injection and stirred until clear colorless solution was obtained.

(b) Required quantity of Hypromellose was dissolved in sufficient quantity of water for injection in separate container and stirred until clear solution obtained; this solution was added to solution of step (a) with stirring.

(c) Required quantity of Boric acid and Sodium chloride were dissolved in sufficient quantity of water for injection in separate container and stirred until clear solution was obtained; this solution was added to solution of step (a) with stirring.

(d) Required quantity of Benzalkonium chloride was dissolved in sufficient quantity of water for injection in separate container and stirred until clear solution was obtained; this solution was added to solution of step (a) with stirring to obtain a final solution.

(e) The pH of final solution obtained as per step (d) was adjusted to 6.5 with required quantity of IN NaOH or 0.1N HCL stock solution and final volume of desired batch size was made up with sufficient quantity of water for injection.

(f) The solution of step (e) was then filtered through 0.22 μ filter.

(g) Accurately weighed quantity of Prednisolone acetate (micronized and sterilized) was added to filtered solution of step (f) under laminar air flow unit and homogenized to obtain a final sterile suspension. The formulation of example 1 was further subjected to stability studies at 40°C/NMT25%RH, and were analyzed at an intervals of 1M, 2M & 3M and at 25°C/40%RH, were analyzed at an intervals of 1M and 3M, the results obtained are presented in Table No. 3. Example 2

Table No. 2: Ophthalmic Suspension containing Moxifloxacin Hydrochloride Eq. to Moxifloxacin (0.5% w/v dissolved) & Prednisolone acetate (0.12 % w/v suspended)

Figure imgf000010_0001

Manufacturing process:

A formulation as shown in table 1 was prepared as follows:

(a) Accurately weighed quantity of Moxifloxacin Hydrochloride and required quantity of Hydroxypropyl betacyclodextrin, Disodium edetate, Sodium metabisulfite, Polysorbate 80 were introduced into suitable container and dissolved it in sufficient water for injection and stirred until clear colorless solution was obtained.

(b) Required quantity of Hypromellose was dissolved in sufficient quantity of water for injection in separate container and stirred until clear solution obtained; this solution was added to solution of step (a) with stirring. (c) Required quantity of Boric acid and Sodium chloride were dissolved in sufficient quantity of water for injection in separate container and stirred the mixture till clear solution was obtained; this solution was added to solution of step (a) with stirring to obtain a final solution.

(d) Required quantity of Benzalkonium chloride was dissolved in sufficient quantity of water for injection in separate container and stirred until clear solution was obtained; this solution was added to solution of step (a) with stirring to obtain a final solution.

(e) The pH of final solution obtained as per step (d) was adjusted to 6.5 with required quantity of IN NaOH or 0.1N HCL stock solution and final volume of desired batch size was made up with sufficient quantity of water for injection. (f) The solution of step (e) was then filtered through 0.22 μ filter.

(g) Accurately weighed quantity of Prednisolone acetate (micronized and sterilized) was added to filtered solution of step (f) under laminar air flow unit and homogenized to obtain a final sterile suspension.

The formulation of example 2 was further subjected to stability studies at 40°C/NMT25%RH, and were analyzed at an intervals of IM, 2M & 3M and at 25°C/40%RH, were analyzed at an intervals of IM and 3M, the results obtained are presented in Table No. 4.

Table No.3: Moxifloxacin hydrochloride equivalent to Moxifloxacin base & Prednisolone Acetate Ophthalmic Suspension (0.5% w/v & 1.0% w/v) finished product analysis data - initial and on stability

Stability Condition 40°C/NMT25%RH 25°C/40%RH

Test Specification Initial IM 2M 3M IM 3M parameters (Proposed)

Description Pale yellow Pale Pale Pale yellow Pale Pale to yellow yellow yellow yellow colour yellow yellow colour colour colour colour suspension colour colour suspension suspension suspension suspension suspension suspension

Moxifloxacin NLT 90.0 % 99.7 99.1 98.8 98.5 99.3 99.0 Assay in% & NMT

110.0 %

Prednisolone NLT 90.0 % 98.5 98.1 98.0 97.5 98.2 98.1 Acetate & NMT Assay in% 110.0 %

Preservative NLT 60.0 % 95.9 95.4 95.2 95.3 95.8 95.3 Content in % & NMT

120.0 %

pH 5.0-7.0 5.81 5.72 5.71 5.56 5.81 5.93

Osmolality 270-330 311 312 312 316 303 311 (mOsml kg)

M: Month(s)

NLT: Not less than

NMT: Not more than RH: Relative Humidity

Table No.4 Moxifloxacin hydrochloride equivalent to Moxifloxacin base & Prednisolone Acetate Ophthalmic Suspension (0.5% w/v & 0.12% w/v) finished product analysis data - initial and on stability

Stability Condition 40°C/NMT25%RH 25°C/40%RH

Test Specification Initial 1M 2M 3M 1M 3M parameters (Proposed)

Description Pale yellow Pale Pale Pale Dark Pale Pale to yellow yellow yellow yellow yellow yellow yellow colour colour colour colour colour colour colour suspension suspension suspension suspension suspension suspension suspension

NLT 90.0 % 98.4 98.5 98.1 97.6 98.5 97.9

Moxifloxacin & NMT

Assay in% 110.0 %

Prednisolone NLT 90.0 % 98.0 98.1 97.7 97.2 97.9 97.5 Acetate & NMT

Assay in% 110.0 %

Preservative NLT 60.0 % 95.8 94.7 95.1 97.8 95.2 93.2 Content in % & NMT pH 5.0-7.0 5.86 5.73 5.66 5.56 5.83 5.72

Osmolality 270-330 308 313 296 311 310 310 (mOsml kg)

M: Month(s)

NLT: Not less than

NMT: Not more than

RH: Relative Humidity

Claims

We claim:
1. A stable pharmaceutical composition comprising an effective amount of Moxifloxacin or its pharmaceutically acceptable salts thereof and an effective amount of Prednisolone or pharmaceutically acceptable esters or salts thereof and pharmaceutically acceptable excipients.
2. The composition of claim 1, wherein the composition comprises from about 0.05 to about 5 % (w/v) of Moxifloxacin Hydrochloride.
3. The composition of claim 1, wherein the composition comprises from about 0.1 to about 10 % (w/v) of Prednisolone acetate.
4. The composition of claim 1, wherein said composition is intended for ocular use.
5. The composition of claim 1, wherein the pharmaceutically acceptable excipients are selected from group consisting of buffering agents, preservatives, tonicity-adjusting agents, antioxidants, pH-adjusting agents, chelating agents, viscosity modifiers, wetting agents, solubilizing agents and combination thereof.
6. The composition of claim 1, wherein the composition has a pH in the range from 5.0 to 7.0.
7. The composition of claim 1, wherein the composition has an Osmolality in the range from 270 to 330 mOsml /kg.
8. A process for preparation of a pharmaceutical composition comprising a steps of: (a) dissolving Moxifloxacin Hydrochloride and pharmaceutically acceptable excipients in water for injection to form a solution; (b) adjusting pH of said solution in the range of 5.0 to 7.0 with pH-adjusting agents; (c) filtering the solution and (d) adding the Prednisolone acetate to the filtered solution followed by homogenization to obtain a final sterile suspension.
9. A method of treating ocular infections, comprising administering to an affected eye of patient a combination of an effective amount of Moxifloxacin or its pharmaceutically acceptable salts thereof and an effective amount of Prednisolone or pharmaceutically acceptable esters or salts optionally together with pharmaceutically acceptable excipients.
10. The method of claim 9, wherein said ocular infections are conjunctivitis, ophthalmic neonatorum, trachoma, corneal ulcers, keratitis, keratoconjunctivitis, endophthalmitis, infectious uveitis and combinations thereof.
PCT/IB2012/056151 2011-11-04 2012-11-05 Fixed dose combination containing moxifloxacin and prednisolone for treatment of ocular infections WO2013065029A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
IN2666/CHE/2011 2011-11-04
IN2666CH2011 2011-11-04

Publications (1)

Publication Number Publication Date
WO2013065029A1 true WO2013065029A1 (en) 2013-05-10

Family

ID=47326262

Family Applications (2)

Application Number Title Priority Date Filing Date
PCT/IB2012/056151 WO2013065029A1 (en) 2011-11-04 2012-11-05 Fixed dose combination containing moxifloxacin and prednisolone for treatment of ocular infections
PCT/IB2012/056149 WO2013065028A1 (en) 2011-11-04 2012-11-05 Fixed dose combination containing azithromycin and loteprednol for treatment of ocular infections

Family Applications After (1)

Application Number Title Priority Date Filing Date
PCT/IB2012/056149 WO2013065028A1 (en) 2011-11-04 2012-11-05 Fixed dose combination containing azithromycin and loteprednol for treatment of ocular infections

Country Status (1)

Country Link
WO (2) WO2013065029A1 (en)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9827191B2 (en) 2012-05-03 2017-11-28 The Johns Hopkins University Compositions and methods for ophthalmic and/or other applications
AU2013256130B2 (en) 2012-05-03 2017-12-21 Johns Hopkins University, The Pharmaceutical nanoparticles showing improved mucosal transport
CA2900652A1 (en) 2013-02-15 2014-08-21 Kala Pharmaceuticals, Inc. Therapeutic compounds and uses thereof
US9688688B2 (en) 2013-02-20 2017-06-27 Kala Pharmaceuticals, Inc. Crystalline forms of 4-((4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxyquinazolin-7-yl)oxy)-1-(2-oxa-7-azaspiro[3.5]nonan-7-yl)butan-1-one and uses thereof
US9890173B2 (en) 2013-11-01 2018-02-13 Kala Pharmaceuticals, Inc. Crystalline forms of therapeutic compounds and uses thereof
BR112015020139A2 (en) 2013-02-20 2017-07-18 Kala Pharmaceuticals Inc compounds and therapeutic uses thereof
CN108530458A (en) 2013-11-01 2018-09-14 卡拉制药公司 Crystalline forms of therapeutic compounds and uses thereof
WO2018048747A1 (en) 2016-09-08 2018-03-15 Kala Pharmaceuticals, Inc. Crystalline forms of therapeutic compounds and uses thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060183698A1 (en) * 2004-06-07 2006-08-17 Ista Pharmaceuticals, Inc. Ophthalmic formulations and uses thereof
AU2003248033B2 (en) * 1998-09-30 2007-01-18 Alcon Laboratories, Inc. Antibiotic Compositions for Treatment of the Eye, Ear and Nose
US20090137539A1 (en) * 2007-11-27 2009-05-28 Alcon Research, Ltd. Topical ophthalmic or otic solution formulations containing moxifloxacin hydrochloride and dexamethasone phosphate

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6239113B1 (en) * 1999-03-31 2001-05-29 Insite Vision, Incorporated Topical treatment or prevention of ocular infections
US20050095205A1 (en) * 2003-10-31 2005-05-05 Ramesh Krishnamoorthy Combination of loteprednol etabonate and tobramycin for topical ophthalmic use
CN101317847B (en) * 2007-06-06 2010-10-13 深圳市瑞谷医药技术有限公司 Medicament composition for eyes or nose, and uses thereof

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2003248033B2 (en) * 1998-09-30 2007-01-18 Alcon Laboratories, Inc. Antibiotic Compositions for Treatment of the Eye, Ear and Nose
US20060183698A1 (en) * 2004-06-07 2006-08-17 Ista Pharmaceuticals, Inc. Ophthalmic formulations and uses thereof
US20090137539A1 (en) * 2007-11-27 2009-05-28 Alcon Research, Ltd. Topical ophthalmic or otic solution formulations containing moxifloxacin hydrochloride and dexamethasone phosphate

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
None

Also Published As

Publication number Publication date
WO2013065028A1 (en) 2013-05-10

Similar Documents

Publication Publication Date Title
AU2004206755B2 (en) An otorhinological delivery device
CA2472188C (en) Polymeric gel system for the controlled delivery of codrugs
US5811446A (en) Prophylactic and therapeutic methods for ocular degenerative diseases and inflammations and histidine compositions therefor
JP4718445B2 (en) Formulations for nasal sinusitis treatment
US20160228357A1 (en) Auris Formulations for Treating Otic Diseases and Conditions
DE60123055T2 (en) A method of treating inflammation-related conditions of the eye
US20070264310A1 (en) Solvating system and sealant for medical use in the middle or inner ear
CN101400355B (en) Povidone iodine ophthalmic composition
US20050153946A1 (en) Temperature-stable formulations, and methods of development thereof
FI91217C (en) ophthalmic carrier composition for pharmaceutical or diagnostic agent
CN1231218C (en) Use of medicinal composition in preparing medicine for treating middle ear infections
KR101477329B1 (en) Controlled release corticosteroid compositions and methods for the treatment of otic disorders
US20140171490A1 (en) Method and Device for Ophthalmic Administration of Active Pharmaceutical Ingredients
US9603796B2 (en) Controlled release antimicrobial compositions and methods for the treatment of otic disorders
US5516808A (en) Topical cellulose pharmaceutical formulation
JP2010280695A (en) Improved delivery of drugs to mucosal surfaces
JP2011528716A (en) Method for the treatment of structure regulation and innate immune system modulating compounds and ear disorders controlled release ear
JP2018090641A (en) Conveniently implantable sustained release drug composition
JP2010520210A (en) The methods and compositions for normalizing meibomian gland secretions
CN102319209B (en) Nasal pharmaceutical formulations and methods of using the same
JPH09504294A (en) Ear, suspensions of loteprednol etabonate diisocyanate for use in the treatment of ocular or nasal
ES2641621T3 (en) ophthalmic compositions comprising graft copolymers of polyvinyl caprolactam-polyvinylacetate-polyethylene glycol (SOLUPLUS)
JP4856392B2 (en) Preservatives and aqueous compositions containing the same
US8852626B2 (en) Controlled-release CNS modulating compositions and methods for the treatment of otic disorders
HU0302690A2 (en) Antibacterial aqueous pharmaceutical compositions

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 12798865

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase in:

Ref country code: DE

122 Ep: pct app. not ent. europ. phase

Ref document number: 12798865

Country of ref document: EP

Kind code of ref document: A1