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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
     includes packaging materials

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

B. Amsden                      CHEE 440

B. Amsden   CHEE 440

B. Amsden   CHEE 440
Bacterial Endospores

B. Amsden        CHEE 440
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
            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
      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

     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

B. Amsden   CHEE 440
Z value
degrees of temperature/dose change required to achieve a tenfold
decrease in D

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

   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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