STERILIZATION

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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

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Viruses
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Bacteria
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Bacterial Endospores
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Yeast and Mould
aspergillus
penicillium
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Sterilization Methods

• steam sterilization
• conducted in an autoclave
• method of choice
• 121 ?C, 20 minutes
• dry heat
• less effective than moist heat
• 170 ?C, gt 2 hours
• used to sterilize equipment

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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

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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

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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

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Kinetics of Cell Inactivation

• death rate follows first order kinetics

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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.

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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