Annexure-I

Master Formula

PRODUCT: BRIMOLOL OPHTHALMIC SOLUTION.

BATCH SIZE: 100 LITRES (20,000 UNITS)

S. Batch Size Remarks

Ingredients Per ml
No. 100 litres Specifications
Supplier
1. Brimonidine Tartrate 2.000 mg 200.00 gm
Specification.

2. Timolol Maleate 6.830 mg 683.00 gm USP

Dibasic Sodium Phosphate

3. 5.313 mg 513.30 gm B.P/USP
heptahydrate
Monobasic Sodium
4. 5.313 mg 513.30 gm B.P/USP
Phosphate Monohydrate

5. Benzalkonium Chloride 0.040 mg 4.0000 gm B.P/USP

6. Sodium Chloride 6.300 mg 630.00 gm B.P/USP

7. Disodium Edetate 0.130 mg 13.000 gm B.P/USP

8. Sodium Hydroxide qs qs B.P/USP

9. Purified water q.s to make 1.00 ml 100 litres B.P/USP

________________ ___________________
Production Manager Quality Control Manager
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PRODUCT: BRIMOLOL OPHTHALMIC SOLUTION.

BATCH SIZE: 100 LITRES (20,000 UNITS)

METHOD OF MANUFACTURE

GMP CHECK LIST

The walls, floor, ceiling lights are clean and in satisfactory condition. Ensure that
each equipment used in the manufacturing must be thoroughly cleaned and
properly logged. All extraneous materials including materials from previous batches
have been removed from the area.
Attach sterilization charts to the manufacturing record.

PRECAUTIONS

All operators should wear mask, rubber gloves, and uniform with sleeves tucked in
during all process of manufacture.
Loteprednol etabonate may cause irritation. Wear gloves, eye protection, while
handling this material. Avoid breathing dust. Wash hand and face well before eating
or smoking after handling this material.
1.0 METHOD:
The manufacturing of Brimonidine Tartrate Timolol is carried out in three parts.

PART A (Preparation of Bulk Solution) :

1.1 Take purified water about 90 liters in S.S mixing vessel and dissolve the
following materials.
Sodium Phosphate Diabasic Heptahydrate 513.30 gm
Sodium Chloride 630.00 gm
Disodium Edetate 0.130 gm
1.2 Start passing nitrogen gas filtered through 0.22um Filter in the above
solution.
1.3 Add benzalkonium solution 4.0000 gm to the bulk solution. Rinse the
Benzalkonium container with sufficient purified water and add the rinse to the
bulk solution.
1.4 Bring the temperature of bulk solution to room temperature by passing filtered
Nitrogen gas.

________________ ___________________
Production Manager Quality Control Manager
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 PART B (Preparation of Brimonidine Tartrate / Timolol Solution) :
1.5 Take about 5 liters fresh purified water in a glass jar., cool down to room
temperature by passing filtered nitrogen gas. Check the temperature it
should not exceed 30 (degree Centigrade).
1.6 Add Brimonidine Tartrate 200 gm and Timolol Maleate 683.0 gm to the glass
jar containing cool water and mix by passing the filtered nitrogen gas till a
clear solution is obtained.

PART C (Final Preparation) :

1.7 Add the Brimonidine Tartrate + Timolol to the bulk solution. Mix under
mitrogen atmosphere till a clear solution is resulted.
1.8 Make up the volume with freshly purified water cooled down to 30 (Degree
Centigrade) under nitrogen atmosphere.
1.9 Check the pH of the solution.

pH range : 7.2 7.6

2.0 Adjust the pH if necessary with 1N sodium hydroxide.
pH: ..
Quantity of Sodium Hydroxide 1N used .
2.1 Submit the sample to Q.A for bulk analysis.
2.2 After Q.A satisfactory results, filter the solution through sterilized 0.22um filter
paper under aseptic condition and collect the filtered solution in pre-sterile
storage container.
2.3 Perform the leak test of the filter solution.
2.4 Fill the solution in pre-sterilized plastic bottle under aseptic condition.
2.5 Submit the filtered bottle for chemical and stability test to Q.A.

________________ ___________________
Production Manager Quality Control Manager
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