Bril Suspension (90 ml)

Ibuprofen
PART II QUALITY DOCUMENT
P3: MANUFACTURE

P3 MANUFACTURE

1- Applicant’s:

Name : Briell pharmaceuticals (Pvt.) Ltd.

Address : 538-C,Sundar Industrial Estate, Multan Road, Lahore-Pakistan
Phone : 042-35297545
E-mail : info@briellpharm.com

2- Manufacturer’s*:
Name : Briell pharmaceuticals (Pvt.) Ltd.
Address : 538-C,Sundar Industrial Estate, Multan Road, Lahore-Pakista n
Phone : 042-35297545
E-mail : info@briellpharm.com

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 Bril Suspension (90 ml)
Ibuprofen
PART II QUALITY DOCUMENT
P3: MANUFACTURE
P 3.1 Batch Formula
The batch formulation for Bril Suspension is provided below:

Product Name: Bril Suspension

Batch Size: 2000 L

Composition: Each 5 ml contains:

Ibuprofen ......................…...100mg

MASTER FORMULATION

Composition Quantity
Sr.
Ingredients (Each 5 ml Per Batch Specs. Function
No
Contains) 2000 Liter
ACTIVE INGREDIENT
1.
Ibuprofen * 100 mg 40.00 kg USP API
EXCIPIENTS
2. Sucralose 35 mg 14.00 Kg BP Sweetener

3. Citric Acid Monohydrate 10mg 4.00 Kg BP pH Stabilizer

4. Sodium Benzoate
5mg 2 Kg BP Preservative
5. Methyl Paraben Sodium 3mg 1.2Kg BP pH stabilizer

6. Propyl Paraben Sodium 1.5 mg 0.6 Kg BP pH stabilizer

7. CMC 13 mg 5.3 Kg BP Suspending

agent
8. Polysorbate-80 (Tween 80) 5 mg 2.0Kg BP Emulsifier

9. Sodium EDTA 5 mg 2.0 kg BP Antioxidant

10. Sodium Saccharine mg 0.6 kg BP Sweetener

11. Xanthan Gum 12.50 mg 4.0 Kg BP Thickener
Sunset Yellow color Coloring
12. 5.00 mg 0.3 Kg BP
water soluble agent
Aerosil-200 5.00 mg 1.50 Kg In-house Suspending
13.
agent
Orange Flavor 6mg 2.7Kg In-house Flavoring
14.
agent
Purified water (Quantity
5.00 ml 2000.00 L
Sufficient)

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 Bril Suspension (90 ml)
Ibuprofen
PART II QUALITY DOCUMENT
P3: MANUFACTURE

Note:
* Final quantity of API to be added depends on the analytical assay as per QC results

P 3.2 Manufacturing Process and Process Control

a. Manufacturing Process Flow Diagram

A flow diagram representing the manufacturing process of Bril Suspension and

narrative description of manufacturing process along with the in process controls is
provided in this section.

See Next Page

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 Bril Suspension (90 ml)
Ibuprofen
PART II QUALITY DOCUMENT
P3: MANUFACTURE

Preparation of ibuprofen
dispersion
Mesh # 40
Filter sorbitol solution
Sieve Ibuprofen through

Preparation of Simple Continue mixing for 90 min using

Syrup Silverson in bulk manufacturing tank

Take Purified Water in

Mixing should be done until Add Polysorbate
S.S container and run
uniform dispersion obtained 80
Silverson
homogenizer.
Ibuprofen Dispersion
Methyl Paraben Sodium
In Bulk Manufacturing Tank
Propyl Paraben Sodium
Sucralose Addition of the gum
Add xanthan gum in
glycerin and mix it
complexly then transfer
Sodium Benzoate it.
Sucrose, Tri Sodium Citrate
Dihydrate and Sodium Simple Syrup
Chloride Bulk Manufacturing
Tank

Bulk Sample 400 ml to QC.

Addition of the citric acid

Add flavor, volume make up, final mix solution and color in the bulk
After QC Release manufacturing tank

Bottle blowing
Suspension filling
Labelling
Packing

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 Bril Suspension (90 ml)
Ibuprofen
PART II QUALITY DOCUMENT
P3: MANUFACTURE

P 3.2 Manufacturing Process and Process Control

b. Manufacturing Process Control

Description of manufacturing process along with process controls is provided as under.

MANUFACTURING INSTRUCTIONS

I. Good Manufacturing Practices:

To ensure a quality production, all current manufacturing practices should be

followed such as:

i. Area and Equipment

ii. Personnel
iii. Raw Material & Packing Material
iv. Production and Process Control

EQUIPMENT USED IN MANUFACTURING

Process
Equipment’s Used Capacity
Stage
Weighing Balance (Top Loading) 1200gm
Dispensing Weighing Balance (Platform) 150.00 Kg
Dispensing Hood N/A
Preparation of Silverson Homogenizer with Mixing
2000L
Simple Syrup Tank
Barrel Pump 3 HP
Preparation of
Muslin Cloth N/A
Ibuprofen
Dispersion Sieve Mesh Size#40 Mesh Size# 40

Addition of the S.S container N/A

Gum Barrel Pump 3 HP
Addition of Citric S.S container N/A
Acid Solution Stirrer N/A
Addition Of Color S.S Container N/A
And Flavor
Final Mixing and Silverson Homogenizer 1200 RPM
Volume make up Manufacturing Tank 2000 L
Bottle Blowing Bottle blowing machine N/A

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 Bril Suspension (90 ml)
Ibuprofen
PART II QUALITY DOCUMENT
P3: MANUFACTURE

Filling Machine Filling Machine 2500/hr

Labeling Labelling Machine N/A
Packing Conveyor Belt N/A

Dispensing

 Dispense the materials as per manufacturing order in the presence of QA, production
and raw material store representatives.
 Ensure the proper protective measure of personals like mask, gloves etc.
 Check the temperature & humidity of area and balance calibration.
 For weighing purpose, ensure that there are no chances of cross contamination.
 Ensure the use of separate scoop, spoon, and spatula for weighing purpose.

Precautions:
Manufacturing process must be carried strictly according to the Standard
Manufacturing Procedure and any deviation from the process must be authorized by
the Production Manager & Quality Control Manager.
Prior to start the manufacturing process check that manufacturing area and equipment
are cleaned and ensure that Area Approval and Line Clearance Certificate are issued
by the Quality Assurance Department.
All equipment to be used must be cleaned and absolutely dry and have the cleaned
status and labeled with Product Name, Batch Number, stage and date.
Before going to start manufacturing process ensure that all active and inactive raw
materials must be checked and weighed.
Prior to start manufacturing process ensure that personnel hygiene wearing area
uniform, face mask and surgical gloves.

Issuance, Dispensing and Transfer of Raw Material:

Raw Material are issued, dispensed and transferred to manufacturing area where Raw
materials must be properly labeled and stored in the mfg. area before manufacturing
process under controlled conditions.

Pre-processing Operations:
Before manufacturing process ensure area and machine cleaning, LOG Book completion
and environmental conditions.
Before manufacturing process ensure the availability of Area Approval and Line
Clearance Certificate issued by Quality Assurance Department.

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 Bril Suspension (90 ml)
Ibuprofen
PART II QUALITY DOCUMENT
P3: MANUFACTURE

MANUFACTURING PROCEDURE

1. Preparation of Simple Syrup:

Materials Quantity
Methyl Paraben Sodium 1.20 kg
Propyl Paraben Sodium 0.6 kg
Sucralose 14.00 kg
Sodium benzoate 2.0 kg
Sodium saccharine 0.6 kg
Sodium EDTA 2.0 kg
Citric Acid Monohydrate 4.0 kg
Tween-80 2.00 Kg
Color Sunset Yellow 0.3Kg

1.1 Take Purified water in S.S.container and run silverson mixer in it.
1.2 Slowly add methyl paraben sodium at and mix it.
1.3 Then Slowly add propyl paraben sodium to solution and mix it.
1.4 Now add sucralose to solution and mix it.
1.5 Add sodium benzoate into the above solution and mix it well.
1.6 Add Tween 80, Sodium EDTA and sunset yellow color into the solution
obtained at step 1.5 and continues mix it until it dissolves completely.

2. Add following material in step a and mix for 30minutes:

Materials Quantity
Aerosil-200 1.5 Kg

* Final quantity of API depends on the analytical assay as per QC results

3. Add following material in manufacturing tank and mix for 30 minutes.

Materials Quantity
Ibuprofen 41.19 Kg

4. Then add following materials with continuous stirring and mix for 20 minutes.

Material Quantity
Xanthan Gum 4.0 Kg

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 Bril Suspension (90 ml)
Ibuprofen
PART II QUALITY DOCUMENT
P3: MANUFACTURE

CMC 5.30 Kg

3.1 Slowly add xanthan gum in glycerin and mix it completely till homogeneous
dispersion is obtained.

5.

Material Quantity
Orange Flavor 2.7 kg
Purified water 2000.00 L

5.1. Transfer the solution after filtration through muslin cloth into the S.S.
manufacturing tank with continuous mixing.

7. Filling:

7.1 Intimate QA department for sampling and get release for filling.
7.2 After receiving QC approval, transfer the bulk in filling area.
7.3 Set filling and labelling machine according to product specification. After
getting line clearance from QA department, start filling
7.4 Perform all the In-Process Quality Control Tests (Volume variation, cap sealing,
label pasting etc).
7.5 Fill the batch as per filling specifications.

8. Packaging:
8.1 Generate the packing material requisition for cartons and shippers.
8.2 After getting line clearance from Q.A department and packing pharmacist, start
printing of cartons.
8.3 Now pack bottles in cartons and then in shippers.

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 Bril Suspension (90 ml)
Ibuprofen
PART II QUALITY DOCUMENT
P3: MANUFACTURE

P 3.3 Control of Critical Steps and Intermediates

IN-PROCESS Quality Control Checks

 In-process to check thorough daily Sanitation Control Procedure.

 To check the raw material and packing components to make sure that
complies with standard specifications.

 In process Q.C. to perform the complete analysis of the product.

 In-process Q.A. to check the specified parameters to make sure the

manufacturing procedure is conducted under the prescribed parameters.

 In-process Q.A. to check the volume during filling procedure.

 In-process checking of finished products as per Standards.

 Approval of Release on finished products after complete analysis of the

product as per specifications.

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 Bril Suspension (90 ml)
Ibuprofen
PART II QUALITY DOCUMENT
P3: MANUFACTURE

P 3.3 Control of Critical Steps and Intermediates

IN-PROCESS SAMPLING

Sr.
Tests Specifications
No.
Orange colored smooth suspension with
1. Description
orange flavor and sweet taste.
2. pH 3.6 - 4.6
3. Density 1.060 – 1.085 g/ml at 20°C

4. Identification of Ibuprofen λ max : 221 nm ±2 nm.

Quantitative Assay
5. Each 5 ml contains: 95.0 – 105.0 % of label claim
Ibuprofen………….100mg

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 Bril Suspension (90 ml)
Ibuprofen
PART II QUALITY DOCUMENT
P3: MANUFACTURE

P 3.4 Process Validations and/or Evaluation

Process Validation is performed on the following batches of Bril Suspension:

S. #. Batch No. Mfg. Date Batch Size

1. 39093 11.08.2023 2000 Litre
2. 39095 22.08.2023 2000 Litre
3. 39097 22.08.2023 2000 Litre

The process is sufficiently controlled to produce a uniform product.

PROCESS VALIDATION PROTOCOL & REPORT OF ABOVE BATCHES

(ATTACHED UNDER THIS PAGE)

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