To study the container of rubber closure and prevention of contamination

1. Topic : Evaluation of rubber
closure
Subject : Industrial Pharmacy I
Subject incharge : Prof .Sofiya
Moris
Presented by : ADITI
SURKULE
Roll No:104
Shri. D.D.Vispute College of Pharmacy & Research
Centre

2. INTRODUCTION
• Rubber closures are essential components used to seal containers for
parenteral and other sterile preparations, ensuring product
protection, sterility, and stability.
• Evaluation of rubber closures involves a series of physical, chemical,
and biological tests to determine their suitability, safety, and
compatibility with the drug product.
• These tests confirm that the closures do not interact with the
contents, maintain an effective seal, and comply with pharmacopoeial
standards (IP, USP, BP) for pharmaceutical packaging materials.

3. • Fragmentation test
• Self sealability test
• pH of the aqueous extract
• Light absorption test
• Reducing substance test
• Residue on evaporation
QUALITY CONTROL TESTS FOR RUBBER CLOSURE

4. Wash colsures in 0.2%w/v of anionic surface active agent for
5 min
Rinse 5 times with dist.water
SAMPLE PREPARATION
Add 200ml water and is subjected to autoclave at 119
to 123°C for 20 to 30 min covering with aluminium
foil.
Cool and separate solution from closure ( sol-
A)

5. • Place a volume of water corresponding to the nominal volume 4 ml
in each of 12 clean vials.
• Close the vials with the prepared closures and allow it to stand for 16
hours.
• Using a hypodermic needle with an external diameter of 0.8mm
inject 1 ml of water into the vial and remove 1ml of air.
• Carry out this operation for 4 time
• Pass the liquid in the vials through a filter with a pore size 0.5
• Number of fragments not more than 10 except in case of butly
rubber closures where the number of fragments not more than 15.
Fragmentation test (for aqueous
preparations)

6. Fragmentation test (for dry
preparations)
• Close 12 clean vials with the prepared closures.
• Using a hypodermic needle with an external diameter of
0.8 mm inject 1 ml of water into vial and remove 1 ml of
air.
• Carry out this operation 4 times with new needle.
• Pass the liquid in the vials through a filter with a pore size
of 0.5µm.
• Number of fragments not more than 10 except in the case
of butyl rubber closure where the total number of
fragments not more than 15.

7. SELF-SEAL ABILITY TEST
• Close the vials with the prepared rubber closures.
• For each closure, use a new hypodermic needle (0.8 mm external dia.)
and pierce it 10 times at different sites.
• Immerse the vials upright in 0.1% w/v methylene blue solution.
• No vial should contain any trace of colored solution.

8. • Take 20 ml of solution A and add 0.1 ml of bromothymol blue
indicator.
• Then add a small amount of 0.01 N NaOH—the color changes from
blue to yellow.
• The volume of NaOH required for this color change should not
exceed 0.3 ml.
• Similarly, if 0.01 N HCl is used instead, the volume required should
not exceed 0.8 ml.
H OF AQUEOUS EXTRACT
p

9. Test must be
completed within
4 hours of
preparing
Solution A
Filter Solution A
through 0.5 µm
filter
Measure absorbance
between 220–360
nm
Absorbance
should not
exceed 2.0
Prepare blank
(without closures)
and measure its
absorbance
LIGHT ABSORPTION TEST

10. 1 ml 1M
H2SO4
Reducing
substances
Add 1 gm
of KI
20 Ml of
0.002 M
KMnO4
Boil for 3
minutes
and then
cool
Titrated with 0.01 M
sodium thio-sulphate
solution using starch
as an indicator
20 ml of
solution
A

11. RESIDUE ON EVAPORATION
• Take 50 ml of solution A and evaporate to dryness at 105 °c
• Then weigh the residue, the amount of residue should not more
than 4 mg
RESIDUE ON EVAPORATION