Quality Control Test for Closures

Preparation of Sample

  1. Wash closures in 0.2% w/v of anionic surface active agents for 5 minutes.
  2. Rinse five times with water and add 200 mL water. Subject to the autoclave at 119 to 123°C for 20 to 30 minutes covering with aluminum foil.
  3. Cool and separate solution from closure, hence known as Solution A.

  1. Sterility Test

    When treated closures are subjected to sterilization test at 64-66°C and a pressure of about 0.7 KPa for 24 hours.

  2. Fragmentation Test
    1. For closures for aqueous solution, place a volume of water corresponding to the nominal volume subtracting 4 mL in each of the 12 clean vials.
    2. Close the vials with the prepared closures and allow to stand for 16 hours.
    3. For closures for dry preparations close 12 clean vials with the “prepared” closures.
    4. Using a hypodermic needle, with an external diameter of 0.8 mm, inject 1 mL of water into the vial and remove 1 mL of air.
    5. Carry out this operation four time with new needle each time. Pass the liquid in the vials through a filter with a pores size of 0.5 micrometer.
    6. Number of fragments is not more than 10 except in the case of butyl rubber closures where the total number of fragments is not more than 15.
  3. Self Sealability Test
    1. For each closure, use a new hypodermic needle with an external diameter of 0.8 mm and pierce the closure 10 times, each time at a different site.
    2. Immerse the vials upright in a 0.1% w/v solution of methylene blue and reduce the external pressure by 27 KPa for 10 minutes.
    3. Restore the atmospheric pressure and leave the vials immersed for 30 minutes. Rinse the outside of the vials. None of the vials contains any trace of colored solution.
  4. pH of the Aqueous Extract
    1. 20 mL of solution A is added with 0.1 mL bromothymol blue when it is added with a small amount of 0.01 M NaOH which changes the colour from blue to yellow. The volume of NaOH required is not more than 0.3 mL and if it is done with HCl, the volume of HCl needed should not more than 0.8 mL.
  5. Light Absorption Test

    Note: It must be done within 4 hours of preparing the solution.

    1. It is filtered through 0.5 micrometer filter and its absorbance is measured at 220 to 360 nanometer. Blank is done without closures and absorbance is not more than 2.0.
  6. Reducing Substances
    1. 20 mL of solution A is added with 1 mL of 1 M sulfuric acid and 20 mL of 0.002 M of potassium permanganate and boil for three minutes. Cool and add 1 gram of potassium iodide which is titrated with sodium thiosulfate using starch as an indicator. Blank is done and the difference between titration volumes is not more than 0.7 mL.
  7. Residue on Evaporation
    1. 50 mL of solution A is evaporated to dryness at 105°C. The residue should not be more than 4 mg.