Fluticasone propionate is a synthetic corticosteroid used topically, intranasally, and orally to treat inflammatory conditions. It comes as a nasal spray containing microfine fluticasone propionate in an aqueous suspension. The manufacturing process involves preparing polymer and drug suspensions, mixing them, adding a preservative, adjusting the pH, filtering, and filling into containers. Critical process parameters like mixing speeds and times are controlled. Samples are tested throughout production and storage for quality attributes like assay, pH, and particle size. Stability studies are conducted according to a documented protocol.

1. ANTI-ALLERGIC AFLUTICASONE
NASAL SPRAY

2. Fluticasone propionate
Fluticasone propionate, is a synthetic corticosteroid
drug
Fluticasone propionate, a medium-potency synthetic
corticosteroid, is used topically to relieve
inflammatory and pruritic symptoms of dermatoses,
intranasally to manage symptoms of allergic and non-
allergic rhinitis, and orally for the treatment of
asthma.

3. Some taxonomy and property as follows:
 Chemical Formula C25H31F3O5S
 Molecular Weight 500.57
 Classes Steroids and Steroid Derivatives
 Half life 10 hours
 State White to off-white crystalline solid powder
 Melting point 272-273o C
 water solubility 0.51 mg/L (insoluble)
 Soluble in Ethanol
 pH 7.5 - 9.5
 Protein binding 91%
 Volume of distribution 2.3 to 16.7 L/kg
 Clearance 1093 mL/min

 Categories Anti-inflammatory Agents
Adrenergic Agents
Dermatologic Agents
Bronchodilator Agents
Anti-Allergic Agents

4. CLINICAL PHARMACOLOGY
 Mechanism of Action
 Pharmacokinetics
 Absorption
 Distribution
 Metabolism
 Elimination
 Pharmacodynamics

5. PLAN OF WORK
Fluticasone Nasal Spray, 50 mcg
is an aqueous suspension of
microfine fluticasone propionate
for topical administration to the
nasal mucosa by means of a
metering, atomizing spray pump.

6. PRODUCT DETAILS
 Product Name Fluticasone Nasal Spray BP (50 mcg per Actuation)
 Generic Name Fluticasone Propionet Nasal Spray BP (50 mcg per
Actuation)
 Shelf Life 24 Months(Proposed)
 Half life 10 hours
 Primary Pack 15 g Suspension
 Storage Store at temperature between 15⁰ - 30⁰ C. Do not
freeze. Protect from light.
 Label Claim Each spray delivers:
 Fluticasone Propionate BP 50 mcg
 Composition: Fluticasone Propionate
BP…………………..…..0.05%w/w
 Benzalkonium chloride BP (as preservative)...….0.05%w/w
 Excipients……………………………………….q.s

7. Item no. Ingredient Quantity/
Batch in Kg
Grade Function
1. Fluticasone
Propionate*
(Micronized)
0.020 BP
Active
2. Dextrose
anhydrous
3.000 USP
Tonicity agent
3. MCC and CMC
Sodium
(Avicel RC591)
0.50 BP
Suspending
agent
4. Polysorbate 80
(Super refined
Tween 80)
0.015 BP
Surfactant
5. Benzalkonium
Chloride
0.020 BP
Preservative
6. Disodium
Edetate
0.002 BP
pH Stabilizer
7. Water for
injection
qs to 100% BP
Vehicle
8. Sodium
hydroxide#
0.01 BP
For pH
adjustment

8. Sr. No. Equipment Name
1. Jacketed Manufacturing vessel 50 liter(for cooling WFI)
2. Jacketed Manufacturing vessel 10 liter(for preparation of Dextrose solution)
3. Manufacturing vessel with homogenizer 40 liter(for preparation of polymer suspension phase)
4. SS container 10,2/5, 1 liter
5. Cartridge Filter Assembly with 0.2 micron filter
8. Conical Sieve 200#
9. Sieve 40#
10. Remi Stirrer
11. Float tank 150 liter with stirrer (for storage and holding final suspension)filter
12. Air Jet Cleaning Machine
13. Automatic Four Head Filling Machine
14. Automatic Four Head Crimping Machine
15. Leak Test Apparatus
16. Remi Homogenizer

9. Manufacturing process:
 Preparation of dextrose solution.
 Preparation of polymer
suspension phase.
 Preparation of drug suspension
phase.
 Mixing of drug suspension phase
and polymer suspension phase.
 Preparation of Benzalkonium
chloride solution.

10.  Mixing of Benzalkonium chloride
solution and polymer drug suspension
phase.
 Preparation of Disodium edetate
solution.
 Mixing of Disodium edetate solution
and polymer drug suspension phase.
 PH measurement.
 Final weight and adjustment and
mixing.
 Filtration.

11. Addition In- House Test
1. pH 5.0 to 7.0
2. Osmolality 250-350 mOsm
3. Viscosity in cPs
By Brookfield viscometer
30 to 130 cPs
4. Minimum fill (Net content) Mean NLT 15.0g
Out of 10 containers
5. Weight per ml Between 0.950 to 1.050
6. No. of delivery per container NLT 120 dose.
7. Shot weight(pump delivery) Individual : 85.0-115.0 mg
Mean : 90.0-110.0 mg
8. Particle size by Microscopy 90% particle below 10µm and 100.0% particle
below 30µm.
9. Preservative content
Content of Benzalkonium
chloride
80.0% to 120.0 amount of LC
11. Particulate Matter No black particle Should be present.

12. CRITICAL PROCESS PARAMETERS:-
Process / Parameters Limit
Environment conditions
Relative Humidity
Temperature :
Below 55%
Between 21-25°C
Preparation of Dextrose
Solution:
Mixing time
Frequency of agitator Temperature of filtered Dextrose
solution
:
Record the time
Record the frequency
30oC – 50oC
Preparation of polymer suspension phase:
Avicel RC591addition time
RPM
Temperature of Dextrose solution
:
20-30 minutes
2000-2800 RPM
30oC – 50oC
Preparation of Drug suspension Phase:
Mixing time
Mixing RPM
: 30 minutes
500-1500 RPM

13. Process / Parameters Limit
Mixing of drug suspension and polymer suspension
phase:
Mixing time
Mixing RPM
:
5-15 minutes
2000-2800 RPM
Preparation of Benzalkonium chloride Solution:
Mixing time
Mixing RPM
Temperature of solution
:
Record the time
Record the RPM
Record the
Temperature
Mixing of Benzalkonium chloride solution and polymer
phase:
RPM
Mixing time
:
1500-2800 RPM
2-5 minutes
Preparation of Disodium edetate solution phase:
RPM
Mixing time
: Record the RPM
Record the time

14. Mixing of Disodium edetate solution and Polymer
suspension phase:
RPM
Mixing time
: 1500-2800 RPM
15-30 minutes
Final mixing before filtration:
RPM
Mixing time
:
1500-2800 RPM
15-30 minutes
pH of suspension : 6.00-7.00
Final mixing after filtration:
RPM
Mixing time
: 200-300 RPM
20-30 minutes
Filling:
Fill Weight
Leak Test
No. of Spray per vial
:
Limit : 15.0 g – 15.6 g
There should not be any
leakage

15. Stage Sampling Location & Quantity Test
Manufacturig stage
(Before filtration from 40
litre manufacturing
vessel)
10 ml sample each from
top, middle and bottom
after 15, 22 and 30 minutes.
Assay 95.0 to 115.0 %
Preservative Content 80.0
to 120.0 %
200 ml Composite Sample
(of top, middle and
bottom) after 15, 22 and 30
minutes.
Assay 95.0 to 115.0 %
Preservative content 80.0
to 120.0 %
pH 5.00 to 7.00
Osmolality 250 – 350
mOsm
Weight per ml 0.950 to
1.050 g/ml
Viscosity in cPs 30 to 130
cPs
Manufacturig Stage
(After filtration from Float
Tank)
10 ml sample each from top,
middle and bottom after 15, 22
and 30 minutes.
Description -White to off
white translucent thick
suspension free from lumps.
200 ml Composite Sample (of
top, middle and bottom) after
As per SFG specification

16. DISCUSSION
 The samples of all the three batches should be
subjected for stability.
 A protocol and report should be documented. Any
Incidents/Deviations from the protocol related to
manufacturing process & packing process, equipments
used, sampling, in-process controls and analytical
methods should be authorized and documented in the
batch manufacturing and packing record as well as the
validation report.

17. Referances:
 U.S. Department of Health and Human Services Food
and Drug Administration
 Center for Drug Evaluation and Research (CDER) May
1999
 Revision Bulletin Official February 1, 2011
 FDA, (CBER), Validation of Procedures for Processing
of Human Tissues Intended for Transplantation,
guidance for industry, May 2002.