STERILIZATION by 85QDFT

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									STERILIZATION
The complete destruction of all living organisms and their spores or
their complete removal from the formulation.

All parenterals, as well as otic, nasal, ophthalmic solutions, must be
sterile,
     includes packaging materials

methods
    steam
    dry-heat
    filtration
    gas
    ionizing radiation


B. Amsden                      CHEE 440
Viruses




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Bacteria




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Bacterial Endospores




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Yeast and Mould




aspergillus       penicillium




B. Amsden             CHEE 440
Sterilization Methods
steam sterilization
    conducted in an autoclave
    method of choice
    121 C, 20 minutes

dry heat
     less effective than moist heat
     170 C, > 2 hours
     used to sterilize equipment




B. Amsden                      CHEE 440
Heat Resistances
     method determined by nature of micro-organism and
      formulation ingredients
    protocols are developed based on reference organisms of
      known sterilization resistance
micro-organisms possess different resistances to heat
            cell type             resistance
            bacterial endospores may survive hours in
                                 boiling water
            fungal spores        death at > 80 C in 60
                                 min.
            yeasts               survive 20 min at 60C
            bacteria             D60 = 1-5 min
            viruses              rarely survive > 30 min
                                 at 60 C
            protozoa, algae      rapidly die at T > 40 C

B. Amsden                     CHEE 440
Steam Sterilization
Determination of steam sterilization protocol
   first select a reference organism
   determine its D value under defined conditions
   establish initial bioburden
   calculate time of exposure at 121 ºC




B. Amsden                   CHEE 440
Sterilization Methods
Filtration
      used for heat sensitive solutions
      pore sizes range from 14 to 0.025 mm

Gas sterilization
    used in hospitals and industry for thermolabile materials
    ethylene oxide, propylene oxide used
    500-1000 mg/L, 4 - 16 hours at 55 ºC, 50-60 %RH
    need to remove absorbed gas after sterilization

Ionization
     use of gamma rays
     limited application


B. Amsden                     CHEE 440
Kinetics of Cell Inactivation

        death rate follows first order kinetics

                        N t  N0 e  kt




B. Amsden                         CHEE 440
D value

              •   decimal reduction time
              •   time required for 90% reduction in
                  cell count




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Z value
degrees of temperature/dose change required to achieve a tenfold
decrease in D




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Example
Using G. stearothermophilus as a reference organism (D121 = 1.5
min), and an initial bioburden of 1000 spores, determine the
sterilization time required to achieve a 1 in 1,000,000 chance of a
spore surviving using a steam autoclave.




B. Amsden                      CHEE 440
De-pyrogenation
Emphasis is placed on prevention of introduction of pyrogens

Removal
   glassware, metals
      • 250 ºC for 45 minutes
   water
      • oxidation to nonvolatile solvents using potassium
        permanganate, then distill
      • reverse osmosis
   plastics
      • protect against contamination




B. Amsden                     CHEE 440

								
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