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topical ophthalmic suspension containing tobramycin and dexamethasone

A tobramycin, topical technology, applied in the field of ophthalmic anti-infective/anti-inflammatory compositions, treatment of mammals, tobramycin/dexamethasone compositions, can solve slow deacetylation, stability problems, etc. question

Inactive Publication Date: 2016-01-06
ALCON RES LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, as noted above, it was found that ionic interactions of tobramycin with xanthan gum at pH 5 to 6 lead to clumping and / or precipitation of xanthan gum
Additionally, xanthan gum was found to undergo deacetylation slowly during storage, causing stability issues

Method used

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  • topical ophthalmic suspension containing tobramycin and dexamethasone
  • topical ophthalmic suspension containing tobramycin and dexamethasone
  • topical ophthalmic suspension containing tobramycin and dexamethasone

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] The following describes the preparation of tobramycin / dexamethasone / xanthan gum formulations using xanthan gum that has not been deacetylated. The resulting formulations were also evaluated for stability, as explained below.

[0047] Preparation of Xanthan Gum Stock Solutions

[0048] Add hot water to the container. The xanthan gum is weighed and added slowly to the container with mixing. Adjust the temperature to 60°C and mix the xanthan gum and water until homogeneous. Purified water was added to bring the composition to the final target weight and mixed until uniform. The temperature is raised to 70°C before filtration through a suitable fine filter such as a 1.2 μm filter.

[0049] Preparation of Tobramycin / Dexamethasone Formulations Using Xanthan Gum Stock Solutions

[0050] Tobramycin, sodium chloride, boric acid and disodium edetate in the amounts indicated in Table 1A below were added to a portion of purified water and dissolved. Add hydrochloric acid ...

Embodiment 2

[0059] The following describes the preparation of tobramycin / dexamethasone formulations in accordance with the principles of the present invention involving the use of deacetylated xanthan gum.

[0060] Preparation of xanthan gum stock solutions and pretreatment with alkali

[0061] Add hot water to the container. Weigh the xanthan gum and add slowly to the container with mixing. Add 2.5 ml of 1 N NaOH or equivalent per 1 gram of xanthan gum and mix for 20 minutes. Then 1.66 ml of 1 N HCI or equivalent was added per 1 gram of xanthan gum. Purified water was added to adjust the target weight, followed by mixing for 15 minutes. The deacetylated xanthan gum is then filtered through a suitable filter such as a 1.2um filter.

[0062] Preparation of Tobramycin / Dexamethasone Formulations Using Pretreated Xanthan Gum Stock Solutions

[0063] The indicated amounts of tobramycin, sodium chloride, sodium sulfate, edetate disodium, and propylene glycol were added to a portion of ...

Embodiment 3

[0074] Further described herein is the effect of tobramycin on the initial viscosity of the compositions of the present invention and the recovery of viscosity when the compositions are applied to the eye. The formulation shown in Table 3A below was prepared using deacetylated xanthan gum, which is a different batch of formulation number 108536 described in Table 2A above and is representative of the composition of the present invention. at shear rate 6sec -1 The initial viscosity of the formulation was measured and determined to be 42 cps.

[0075] Table 3A

[0076] components

%w / v

Function

Tobramycin

0.3

active agent

Dexamethasone (micronized)

0.1

active agent

Benzalkonium chloride

0.01

preservatives

Tyloxapor

0.05

lubricant

Edetate Disodium

0.01

Preservative additives

Sodium chloride

0.23±0.04

tonicity agent

Sodium sulfate

0.25

tonicity agent

...

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Abstract

An ophthalmic pharmaceutical composition containing tobramycin, dexamethasone and deacetylated xanthan gum is described. The composition provides longer ocular retention to enhance the ocular bioavailability of tobramycin and dexamethasone. In a preferred embodiment, the composition also provides an improved suspension of dexamethasone. The concentration of ionizable species in the composition is controlled in order to prevent precipitation of xanthan gum due to ionic interactions between tobramycin and xanthan gum, while allowing viscosity recovery when the composition is topically applied to the eye. The use of deacetylated xanthan gum is disclosed in order to avoid formulation instability due to pH changes during storage.

Description

Background of the Invention [0001] The present invention relates to the field of ophthalmic anti-infective / anti-inflammatory compositions and related methods of treating mammals, particularly humans. More specifically, the present invention relates to novel ophthalmic anti-infective / anti-inflammatory compositions containing tobramycin and dexamethasone. [0002] The combination of tobramycin and dexamethasone is known for the treatment of ophthalmic infections and accompanying inflammation. Similarly, combinations of these compounds are also known for the treatment of inflammation and the prophylactic treatment (ie, prevention or amelioration) of infections, such as those associated with ophthalmic surgery. Products of this type are sold by Alcon Laboratories, Inc. in the U.S. and other countries as (Tobramycin 0.3% / Dexamethasone 0.1%) ophthalmic suspension for sale. This product has been available in the United States since 1988. Over the years, it has been widely accept...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/00A61K47/02A61K47/36A61K31/70
CPCA61K9/0048A61K9/0051A61K31/573A61K31/70A61K31/7036A61K47/02A61K47/36A61P27/02A61P29/00A61P31/00A61K2300/00A61K2121/00
Inventor B·P·卡巴拉
Owner ALCON RES LTD