DESC:Title of the Invention
An improved process for the preparation of sterile Brinzolamide.

Field of the Invention
The present invention relates to an improved process for the preparation of sterile Brinzolamide compound of Formula-I.

Background of the Invention
BRINZOLAMIDE (also known as Azopt) is chemically known as (4R)-4-(Ethylamino)-3,4-dihydro-2-(3-methoxypropyl)-2H-thieno[3,2-e]-1,2-thiazine-6-sulfonamide 1,1-dioxide. The molecular formula is C12H21N3O5S3 and the molecular weight is 383.51. The structural Formula is:

AZOPT is a carbonic anhydrase inhibitor indicated for the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma.

US 5378703 A (Alcon Laboratories) discloses Brinzolamide compound and its manufacturing process.

European patent EP 2846845 B1 (Icrom SpA) describes process for preparation of sterile Brinzolamide, wherein detailed experimental procedure not provided.

Therefore, it would be desirable and of paramount importance to have a process for the preparation of sterile Brinzolamide compound of Formula-I, by employing without any impact on environment and control all degradation impurities by providing detailed experimental procedure.

Summary of the Invention

The present invention provides an improved process for the preparation of sterile Brinzolamide.

In one aspect, the present invention provides an improved process for the preparation of sterile Brinzolamide compound of Formula-I.

which comprises:
(i) placing a bulk powder of non-sterile Brinzolamide in aluminium foil;
(ii) placing the aluminium foil in aluminium canister;
(iii) placing the aluminium canister in Styrofoam box and fill inside with dry ice;
(iv) placing the Styrofoam box inside aluminium tart;
(v) performing gamma-ray sterilization treatment on the bulk powder of Brinzolamide.

In another aspect, the present invention provides an improved process for the preparation of sterile Brinzolamide compound of Formula-I.

which comprises:
(i) placing a bulk powder of non-sterile Brinzolamide in aluminium canister;
(ii) placing the aluminium canister in Styrofoam box and fill inside with dry ice;
(iii) placing the Styrofoam box inside aluminium tart;
(iv) performing gamma-ray sterilization treatment on the bulk powder of Brinzolamide.

BRIEF DESCRIPTION OF THE DRAWINGS
Figure-1 represents 2D and 3D drawings for sterilisation with Aluminium foil in Aluminium Canister.
Figure-2 represents 2D and 3D drawings for sterilisation without Aluminium foil in Aluminium Canister.

Detailed Description of the Invention

Unless otherwise stated, the following terms used in the specification have the meanings given below:

The word ‘Canister’ means a round or cylindrical Aluminium container.

The word ‘Styrofoam’ means thermocol box.

Accordingly, the present invention provides an improved process for the preparation of sterile Brinzolamide compound of Formula I.

The main embodiment of the present invention provides an improved process for the preparation of sterile Brinzolamide as shown below:
In stage-i), placing a bulk powder of non-sterile Brinzolamide in aluminium foil;
In stage-ii), placing the aluminium foil in aluminium canister;
In stage-iii), placing the aluminium canister in Styrofoam box and fill inside with dry ice;
In stage iv), placing the Styrofoam box inside aluminium tart;
In stage v), performing gamma-ray sterilization treatment on the bulk powder of Brinzolamide.

In another embodiment of the present invention provides an improved process for the preparation of sterile Brinzolamide as shown below:
In stage-i), placing a bulk powder of non-sterile Brinzolamide in aluminium canister;
In stage-ii), placing the aluminium canister in Styrofoam box and fill inside with dry ice;
In stage-iii), placing the Styrofoam box inside an aluminium tart;
In stage iv), performing gamma-ray sterilization treatment on the bulk powder of Brinzolamide.

In above sterilization processes, the gamma irradiation temperature used for 25°C to -80°C and the radiation used for 10-30 kGy, preferably 13 to 30 kGy.

Advantages:
a) Aluminium don't break up into harmful microparticles like plastic.
b) Brinzolamide is heat sensitive molecule. Aluminium canisters are maintaining cooling properly, while gamma irradiation.
c) Controlled all degradation impurities.

EXPERIMENTAL PORTION:
The details of the invention are given in the examples provided below, which are given to illustrate the invention only and therefore should not be construed to limit the scope of the invention.

Example 1: Load the Brinzolamide non-sterile compound (5-10 grams) sample into 3 aluminium canisters (50-100 mL) and 80-100 grams of sample into 4 aluminium canisters (250 mL) under nitrogen. Keep the aluminium canisters into thermocol box and fill with dry ice and expose the thermocol box to 13-20 kGy gamma irradiation at 25°C to -80°C (under nitrogen).
The test results are as follows:

S.No Test Results
01. Description White powder
02. Impurity -A (Isomer) 0.07
03. Impurity-B
(Related compound B) 0.1
04. Impurity-C
(Des methyl IMP) 0.05
05. Impurity-D
(Oxo impurity) 0.05
06. Total impurities 0.35
07. Sterility Sterile

Example 2: Load the Brinzolamide non-sterile compound (5-10 grams) sample into aluminium foil and 0.8 Kg to 1.0 Kg of sample into aluminium canister (2.5L) under nitrogen. Keep the canisters into thermocol box and fill with dry ice and expose the thermocol box to 25-30 kGy gamma irradiation at 25°C to -80°C (under nitrogen).
The test results are as follows:

S.No Test Results
01. Description White powder
02. Impurity -A (Isomer) 0.07
03. Impurity-B
(Related compound B) 0.15
04. Impurity-C
(Des methyl IMP) 0.05
05. Impurity-D
(Oxo imp) 0.05
06. Total impurities 0.40
07. Sterility Sterile
,CLAIMS:We claim:

1. An improved process for the preparation of sterile Brinzolamide compound of Formula-I.

which comprises:
(i) placing a bulk powder of non-sterile Brinzolamide in aluminium foil;
(ii) placing the aluminium foil in aluminium canister;
(iii) placing the aluminium canister in Styrofoam box and fill inside with dry ice;
(iv) placing the Styrofoam box inside aluminium tart;
(v) performing gamma-ray sterilization treatment on the bulk powder of Brinzolamide.

2. An improved process for the preparation of sterile Brinzolamide compound of Formula-I.

which comprises:
(i) placing a bulk powder of non-sterile Brinzolamide in aluminium canister;
(ii) placing the aluminium canister in Styrofoam box and fill inside with dry ice;
(iii) placing the Styrofoam box inside aluminium tart;
(iv) performing gamma-ray sterilization treatment on the bulk powder of Brinzolamide.

3. The sterilization process as claimed in claims 1 and 2, wherein radiation temperature is 10 to 30 kGy.

4. The sterilization process as claimed in claims 1 and 2, wherein radiation temperature is preferably 13 to 30 kGy.

5. The sterilization process as claimed in claims 1 and 2, wherein gamma irradiation temperature used for 25°C to -80°C.