SK7084Y1 - Eye drops containing broad-spectrum antibiotics and local glucocorticoid - Google Patents

Abstract

It is described an ophthalmic preparation as broad-spectrum antibiotic that contains 0.1 to 2 % by weight of levofloxacin hemihydrate or a pharmaceutically acceptable salt thereof or a derivative thereof and as a glucocorticoid comprises 0.01 to 1 % by weight of dexamethasone, optionally in the form of a phosphate salt of phosphoric acid, 0.05 to 0.2 % by weight of hyaluronic acid, 0.01 to 3 % by weight of auxiliary substances for adjusting the viscosity, osmolality and pH to 6.5 to 7.5 and the remainder to 100% by weight is water for injections.

Description

The invention relates to an eye instillation based on the combination of a fluroquinolone derivative (broad spectrum antibiotic) with a glucocorticoid, with the addition of a viscoelastic agent in the absence of a preservative.

BACKGROUND OF THE INVENTION

To date, several combination preparations based on a broad-spectrum antibiotic and a local glucocorticoid, such as Spersadex comp. (active ingredients: dexamethasone sodium phosphate, chloramphenicolum), Maxitrol (active ingredients: dexamethasone, neomycin sulphate, polymyxin-B sulphate), Sofàadex (active ingredients: dexamethasone sodium sulphobenzoate, framycetini sulphate, gramicidinum), dumradex (active ingredients) ).

GR1007745B1, which describes ophthalmic pharmaceutical compositions for topical administration with a combination of active ingredients such as levofloxacin and dexamethasone. The combination formulation contains benzalkonium chloride as a preservative, causing various types of allergies in long-term use.

The object of the present invention is to provide an ophthalmic instillation comprising a combination of the active ingredients levofloxacin and dexamethasone, which is sufficiently stable even in the absence of a preservative and provides greater comfort and better tolerability without negatively affecting the corneal epithelium.

The essence of the technical solution

The range of prior art ophthalmic preparations based on a broad-spectrum antibiotic and a local glucocorticoid is expanded to include the preparation according to the invention, which consists in that it contains 0.1 to 2 wt. % levofloxacin (fluroquinolone derivative) or a pharmaceutically acceptable salt or derivative thereof; % dexamethasone (glucocorticoid), or its phosphate salt with phosphoric acid, further 0.01 to 3 wt. % of auxiliary substances to maintain solution viscosity and the remainder to 100 wt. forms water for injection.

The object of the present invention is a formulation comprising levofloxacin and dexamethasone with the addition of a high-elastic agent for prolonged action and in the absence of a preservative for better compatibility.

Other pharmaceutical auxiliaries may be substances from the group of inorganic and organic buffer substances (adjusting the pH of the solution) 0.01 to 3% by weight, inorganic and organic salts, substances adjusting the osmolality of the solution 0.01 to 3% by weight, chelating agents, antioxidants % (vitamin E and sodium thiosulfate) 0.01 to 3 wt. and mixtures thereof.

Viscosity-adjusting aids are carmellose sodium, hydroxypropylmethylcellulose, polyvinyl alcohol, carbomer or hyaluronic acid individually or in admixture.

Excipients which maintain the pH range of 6-8 are boric acid, sodium tertaborate, sodium acetate, sodium hydrogen phosphate, sodium dihydrogen phosphate, sodium citrate, citric acid, tartaric acid, sodium tartrate, trometamol, sulfuric acid, hydrochloric acid, sodium hydroxide individually or in the mixture.

The excipients for adjusting the osmotic pressure are sodium chloride, potassium chloride, calcium chloride, sorbitol, mannitol, glycerol, glucose and sucrose individually or in a mixture.

Combined corticosteroid / antibiotic preparations are indicated by inflammatory processes in the structures of the eye where an anti-inflammatory effect is required together with a concomitant suppression (or risk) of secondary bacterial infection. The advantage of the eye drops of the present invention is also good effectiveness and tolerability of the formulation, which is achieved by not containing a preservative, with sufficient stability of the formulation.

EXAMPLES

Example 1

Composition of eye instillation: Levofloxacin hemihydrate Dexamethasone s.Ph.

Sodium chloride

Disodium hydrogen phosphate Sodium dihydrogen phosphate

5.12 mg (0.5%) mg / ml (0.1%) mg / ml (0.8%)

0.474 mg / ml (0.05%)

0.460 mg / ml (0.05%)

SK 7084 Υ1

Hyaluronic acid HCL / NaOH

Water for injection mg / ml (0.1%)

qs pH = 7 ml

Example 2

Composition of eye instillation: Levofloxacin hemihydrate Dexamethasone s.Ph.

sorbitol

Citric acid

Sodium citrate

Hyaluronic acid HCL / NaOH

Water for injections

5.12 mg (0.5%) mg / ml (0.1%) mg / ml (0.8%)

0.474 mg / ml (0.05%)

0.460 mg / ml (0.05%) mg / ml (0.1%) q.s. pH = 7.1 lml

Example 3

Composition of eye instillation: Levofloxacin hemihydrate Dexamethasone s.Ph.

glycerol

Tartaric acid

Sodium tartrate

Hyaluronic acid Polyvinyl alcohol HCL / NaOH

Water for injections

5.12 mg (0.5%) mg / ml (0.1%) mg / ml (0.8%)

0.474 mg / ml (0.05%)

0.460 mg / ml (0.05%)

0.9 mg / ml (0.1%) 1 mg / ml (0.1%) q.s. pH = 7 ml

All prepared compositions were sufficiently stable even in the absence of a preservative, providing greater comfort to the user, and improved tolerability without adversely affecting the corneal epithelium.

Example 4

Production of sodium hyaluronate solution:

The weighed amount of the components (sodium chloride, disodium hydrogen phosphate, sodium dihydrogen phosphate, sodium hydroxide) according to the size of the production batch is dissolved under aseptic conditions in injection water. After dissolution, an amount of sodium hyaluronate corresponding to the production batch is added. After dissolution, the solution is sterilized at 121 ° C for 20 minutes. Check the pH of the solution at 25 ° C (7.0 - 7.1).

Production of levofloxacin and dexamethasone solution:

A weighed amount of the components (levofloxacin hemihydrate, Dexamethasone s.Ph.) is dissolved in a solution which is sterilized by filtration through a 0.2 µm membrane filter and added to a solution of sodium hyaluronate under aseptic conditions. The resulting solution is adjusted to the desired volume in accordance with the batch size.

PROTECTION REQUIREMENTS

Claims (6)

An ophthalmic preparation based on a broad-spectrum antibiotic and a glucocorticoid, characterized in that it contains 0.1 to 2% by weight of an ophthalmic antibiotic. % levofloxacin in the form of a hemihydrate or a pharmaceutically acceptable salt or derivative thereof; % dexamethasone, optionally in the form of its phosphate salt with phosphoric acid, 0.05 to 0.2 wt. % hyaluronic acid, 0.01 to 3 wt. % of auxiliaries for adjusting the viscosity of the composition, adjusting the osmolality and adjusting the pH to 6.5 to 7.5 and the remainder to 100 wt. forms water for injection. Ophthalmic preparation according to claim 1, characterized in that the pH-adjusting auxiliaries are boric acid, sodium tetraborate, sodium acetate, sodium hydrogen phosphate, sodium dihydrogen phosphate, sodium citrate, citric acid, tartaric acid, sodium tartrate, trometamol, sulfuric acid , hydrochloric acid, sodium hydroxide individually or in admixture. Ophthalmic preparation according to claim 1, characterized in that the viscosity-adjusting aids are carmellose sodium, hydroxypropylmethylcellulose, polyvinyl alcohol or carbomer individually or in admixture. Ophthalmic preparation according to claim 1, characterized in that the osmolality adjuvants are sodium chloride, potassium chloride, calcium chloride, sorbitol, mannitol, glycerol, glucose and sucrose individually or in a mixture. SK 7084 Υ1 Ophthalmic preparation according to claim 1, characterized in that the excipient contains vitamin E or sodium thiosulphate as antioxidants. Ophthalmological preparation according to any one of the preceding claims, characterized by by consisting of Levofloxacin hemihydrate 5.12 mg / ml Dexamethasone s.Ph. 1 mg / ml Sodium chloride 8 mg / ml Disodium hydrogen phosphate 0.474 mg / ml Sodium dihydrogen phosphate 0.460 mg / ml Hyaluronic acid 1 mg / ml HCl / NaOH qs to adjust the pH to 7.0 Water for injections 1 ml.