P2 Pharmaceutical Development

Bril Suspension (90ml)
Ibuprofen
PART II QUALITY DOCUMENT
P2: PHARMACEUTICAL DEVELOPMENT
P 2 PHARMACEUTICAL DEVELOPMENT
Aim of the development studies was to develop a drug product, which is pharmaceutical
equivalent to the reference product Brufen Oral Suspension (60ml).
Manufactured by Abbott Laboratories (Pakistan) Limited.
The Strength of reference product is 100mg/5ml and pack size 60 ml.
Introduction and Overview
Bril Suspension is indicated for the treatment of:
Ibuprofen is indicated for the fast and effective reduction of fever, including post
immunization pyrexia and the fast and effective relief of the symptoms of colds and
influenza and mild to moderate pain, such as a sore throat, teething pain, toothache,
earache, headache, minor aches and sprains.
Commercialization:
The proposed formulation for Bril (Ibuprofen) is for Oral Suspension.
Strength of 100mg/5ml is proposed for commercialization and pack size is 60ml.
Page 1 of 13
Ibuprofen
P 2.1 Information on Development Studies
This section is not required for generic products.
Page 2 of 13
Ibuprofen
P 2.2 Components of Drug Product

This section outlines properties of the drug substance with the potential to influence
the manufacture or performance of the drug product.
P 2.2.1 Active Ingredient
Ibuprofen
Non-steroidal anti-inflammatory drug (NSAID) class of medications. Analgesic and
antipyretic property.
Table: Ibuprofen
Physicochemical Characteristics and Biological Properties
Generic Name Ibuprofen
INN Ibuprofen
Chemical name (±)-2-(p-isobutylphenyl)propionic acid
Molecular
C13H18O2
Formula
Relative
206.28
Molecular Mass
CAS Number (15687-27-1)
Structure
Formula
White to off white crystalline powder having a slight

Description
characteristic odor.
Practically insoluble in water, very soluble in alcohol, in methanol,
Solubility
in acetone and in chloroform; slightly soluble in ethyl acetate.
Ibuprofen has analgesic, antipyretic and anti-inflammatory

properties Ibuprofen inhibits prostaglandin synthesis. In humans,
ibuprofen reduces inflammatory pain, swellings and fever.
Biological
Properties Furthermore, ibuprofen reversibly inhibits platelet aggregation.
The main mechanism of action of ibuprofen is the non-selective,
reversible inhibition of the cyclooxygenase enzymes COX-1 and
COX-2.
Page 3 of 13
Ibuprofen
Excipient Compatibility
Drug-excipient compatibility study was performed to evaluate the compatibility of the
excipients with Ibuprofen. This study was performed to identify any unwanted
interaction between the active pharmaceutical ingredient and the excipients used for
the preparation of pharmaceutical product.
Compatibility Study:
Drug-excipient compatibility study was performed with the excipients stated above to
evaluate the compatibility of the excipients with Ibuprofen. This
study was performed to identify any unwanted interaction between the active
pharmaceutical ingredient and the excipients used in the manufacture of drug product.
The physical compatibility study of Ibuprofen with various excipients was carried out
with an aim to select suitable excipients for a stable and robust formulation.
Procedure:
(i) Containers closures

Amber PET Bottle is used as primary container with Silver plastic cap.
(ii) Sample preparation

A blend of the drug with the excipients in a ratio as provided in the Table was filled in
plain plastic bottle and charged at 40°C±2°C/75%±5%RH. Blend of the API (Ibuprofen)
and Excipients were taken in different ratio. Ibuprofen API and the excipients alone
were also charged to be used as reference. The drug-excipient was mixed uniformly. The
compatibility studies are described in table below:
Table: Drug-Excipient Compatibility Studies
Sr.
Sample Detail Drug: Excipient Ratio
#
1. Ibuprofen Drug alone
2. Sucralose Excipient alone
3. Citric Acid Monohydrate Excipient alone
4. Sodium Benzoate Excipient alone
5. Methyl Paraben Sodium Excipient alone
6. Propyl Paraben Sodium Excipient alone
7. CMC Excipient alone
8. Polysorbate-80(Tween 80) Excipient alone
9. Sodium EDTA Excipient alone
10 Sodium Saccharine Excipient alone
11. Xanthan Gum Excipient alone
13. Color Sunset Yellow Excipient alone
Page 4 of 13
Ibuprofen
14. Flavor Orange Excipient alone

15. Aerosil-200 Excipient alone
P 2.2.2 Excipients
The excipients selected for the manufacture of Bril Suspension (90ml) include:
EXCIPIENTS
Material Name Quantitative Qualitative
Sucralose 630mg BP
Citric Acid Monohydrate 180 mg BP
Sodium Benzoate 90 mg BP
Methyl Paraben Sodium 54 mg BP
Propyl Paraben Sodium 27 mg BP
CMC 238 mg BP
Polysorbate-80(Tween 80) 90 mg BP
Sodium EDTA 90 mg BP
Sodium Saccharine 27 mg BP
Xanthan Gum 180 mg BP
Color Sunset Yellow 13.5 mg BP
Flavor Orange 121 mg BP
Aerosil-200 67.5 mg In-house
Based on scientific literature and prior knowledge of excipients, the above excipient
grades were used in Bril (Ibuprofen) 90ml suspension.
Page 5 of 13
Ibuprofen
P 2.3 Finished Product

P 2.3.1 Formulation Development
Reference Product Information
Market Brand Leader i.e Brufen for Oral Suspension (60ml) Manufactured & Marketed
by Abbott Pharma Pakistan Limited was identified as reference product. A detail of the
reference product is provided in the table:
Details of Reference Listed Drug below:

Label Claim Each 5ml contains:
Ibuprofen …………………….. 100mg
Description Orange colored smooth suspension with flavor orange and
sweet taste.
In-active Sodium Benzoate , Methyl Paraben Sodium,Propyl Paraben Sodium
Ingredients , Sucralose , Polysorbate-80(Tween 80) , , Citric Acid
Monohydrate , Xanthan Gum , Sodium EDTA , CMC, Sodium
Saccharine, Color Sunset Yellow , Flavor Orange , Aerosil-200
Indication and Ibuprofen is indicated for the fast and effective reduction of
Usage fever, including post immunization pyrexia and the fast and
effective relief of the symptoms of colds and influenza and mild
to moderate pain, such as a sore throat, teething pain, toothache,
It is packed in Amber Color PET bottle with white color plastic
Supplied as
closure in a unit carton with insertion of leaflet.
Store in the original package in order to protect from heat, light
Storage
and moisture. Store at 15-30oC.
Distributed by Manufactured by Abbott laboratories Pakistan Limited.
Expiry Date 2 years shelf life
Page 6 of 13
Ibuprofen
Summary of Formulation Development

The development of Bril (Ibuprofen) Suspension is described below. The choice of
excipients is justified and their functions were explained. After taking few trials, Mixing
& Sieving method was chosen as the manufacturing process, as the physical and
chemical properties of mixed trials were within the specification limit.
Choice of Excipients:
Based on the literature search and evaluation of reference product, following excipients
were selected to be used during the product development. The functions of these
excipients are as provided below:
EXCIPIENTS AND THEIR FUNCTIONS

Excipients
Material Name Function
Sucralose Sweetener
Citric Acid Monohydrate Stabilizer
Sodium Benzoate Preservative
Methyl Paraben Sodium pH stabilizer
Propyl Paraben Sodium pH stabilizer
CMC Suspending agent
Polysorbate-80 (Tween 80) Emulsifier
Sodium EDTA Antioxidant
Sodium Saccharine Sweetener
Xanthan Gum Thickener
Sunset Yellow color water soluble Coloring agent
Aerosil-200 Suspending agent
Flavor Orange Oil 888 Flavoring Agent
Page 7 of 13
Ibuprofen
P 2.3.2 Overages
No Overage has been included in the quantity of Ibuprofen
Page 8 of 13
Ibuprofen
P 2.3.3 Physicochemical and biological properties.
The physicochemical and biological characteristics of the drug product, that deemed
important, are given below:
Product Name Bril Suspension (60ml)

Strength 100mg/5ml
Dosage Form Suspension
Route of
For oral use
Administration
Each 5ml contains:
Label Claim
Ibuprofen …… 100mg
Orange colored smooth suspension with flavor orange oil
Description
and taste sweet.
pH 3.6-4.6
Dissolution NLT 80 {Q}
Assay (Content of
90 – 110% of the stated amount.
Ibuprofen)
Ibuprofen is indicated for the fast and effective reduction of
fever, including post immunization pyrexia and the fast and
Biological activity effective relief of the symptoms of colds and influenza and mild
to moderate pain, such as a sore throat, teething pain, toothache,
Commercial Packing is available as Amber color PET bottle
Supplied as with white color plastic cap and finally packed in a Unit
carton with insertion of measuring cup and Leaflet.
Storage “Store below 15-30oC and protect from heat & light"
Page 9 of 13
Ibuprofen
P 2.4 Manufacturing Process Development
Manufacturing Process Development is undertaken to optimize the:

■ Critical aspects of Manufacturing Process
■ Critical Formulation Attributes
■ Available Manufacturing Process options
Selection of the Manufacturing Process:

Bril suspension contains Ibuprofen equivalent to 100mg of Ibuprofen. Strategy
proposed for development of Bril suspension is Mixing & Sieving method.
Formulation development studies were conducted in a step-by-step manner observing

product characteristics and performance parameters as a function of formulation
variables. Based on the results of formulation development studies, critical process
parameters were defined and controls incorporated.
The product development trials were planned in line with physical parameters and
chemical parameters of Ibuprofen suspension by market brand leader
i.e Brufen Oral Suspension (60ml), manufactured & marketed by Abbott Laboratories
Pakistan Limited and the results obtained from pre-formulation compatibility study of
drug and excipients.
Mixing and Sieving Method Trials

Mixing and Sieving method was selected for the development due to ease of
processibility, convenience and being not a tedious process
A series of experimental trials were performed to final the manufacturing process.

Dissolution and physical parameters were used to evaluate the suitability of trial
formulations. The results of physical parameter testing are provided for several batches
and are satisfactory. The results of parameters like pH, density and dissolution testing
and assay of the final product support the excipients used.
Manufacturing Process are developed at first time and routinely use till now.
Refer P3 for detail of Manufacturing Process.
Page 10 of 13
Ibuprofen
P 2.5 Container Closure System
Bril Suspension is available as Orange colored smooth suspension with orange flavor
and sweet taste.
Primary Container:
 Commercial Packing is available as Amber color PET bottle with white color
plastic cap
Secondary Packaging:
 Amber color PET bottle is finally packed in a Unit carton with insertion of
measuring spoon and Leaflet.
Interaction between Container & Product:
■ No reaction is observed in this packaging.
■ It ensures adequate protection from the potential adverse effects of water vapor and
ensures adequate protection from the environment (temperature & light moisture),
as the dosage form is distributed and stored, until its intended expiration date.
■ It does not interact physically or chemically with the drug product in any manner to
alter the strength, quality, or purity beyond the official requirements under the
ordinary or customary conditions of handling, shipment, storage, sale and use.
Refer P7 for detail of packaging material specification.
Page 11 of 13
Ibuprofen
P 2.6 Microbiological Attributes
Manufacturing of drug product is carried under suitable environmental controls and

monitoring activities.
Microbial Testing is established as per USP criteria. Not Applicable for this product.
Page 12 of 13
Ibuprofen
P 2.7 Compatibility
Drug-excipient compatibility study was performed as per the information given in

table: Section P 2.2.1. Drug-excipient compatibility studies are required to identify any
unwanted interaction between the active pharmaceutical ingredient and the excipients
used for the preparation of pharmaceutical product. The physical compatibility study of
Bril with various excipients was carried out with an aim to select suitable excipients for
a stable and a robust formulation.
Stability Data showed that formulation was stable with the excipients used and primary
packaging did not showed unwanted interaction between the active pharmaceutical
ingredient and the excipients/primary packaging.
Subsequent assurance of compatibility is provided by stability data.

(For detail of Stability data, See P8.3).
Page 13 of 13

P2 Pharmaceutical Development

Uploaded by

Copyright:

Available Formats

You might also like

P2 Pharmaceutical Development

Uploaded by

Document Information

Original Description:

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

P2 Pharmaceutical Development

Uploaded by

Copyright:

Available Formats

Bril Suspension (90ml)

The Strength of reference product is 100mg/5ml and pack size 60 ml.

Introduction and Overview

Bril Suspension is indicated for the treatment of:

The proposed formulation for Bril (Ibuprofen) is for Oral Suspension.

Strength of 100mg/5ml is proposed for commercialization and pack size is 60ml.

P 2.1 Information on Development Studies

This section is not required for generic products.

P 2.2 Components of Drug Product

P 2.2.1 Active Ingredient

White to off white crystalline powder having a slight

Ibuprofen has analgesic, antipyretic and anti-inflammatory

(i) Containers closures

(ii) Sample preparation

Table: Drug-Excipient Compatibility Studies

14. Flavor Orange Excipient alone

P 2.3 Finished Product

Details of Reference Listed Drug below:

Summary of Formulation Development

EXCIPIENTS AND THEIR FUNCTIONS

No Overage has been included in the quantity of Ibuprofen

Product Name Bril Suspension (60ml)

P 2.4 Manufacturing Process Development

Manufacturing Process Development is undertaken to optimize the:

Selection of the Manufacturing Process:

Formulation development studies were conducted in a step-by-step manner observing

Mixing and Sieving Method Trials

A series of experimental trials were performed to final the manufacturing process.

Refer P3 for detail of Manufacturing Process.

P 2.5 Container Closure System

Interaction between Container & Product:

■ No reaction is observed in this packaging.

Refer P7 for detail of packaging material specification.

P 2.6 Microbiological Attributes

Manufacturing of drug product is carried under suitable environmental controls and

Drug-excipient compatibility study was performed as per the information given in

Subsequent assurance of compatibility is provided by stability data.

You might also like