Contamination

Question 1

What are the Different Types of Contamination?

Answer 1

• Product Related
• Foreign Material

Question 2

Describe Product Related Contamination

Answer 2

• Impurities arise during storage
  
  • Chemical instability of the pharmaceutical substance
    
    • Chemical decomposition catalysed by light, traces of acid or alkali, traces of metallic impurities, air oxidation, carbon, dioxide and water vapours

Question 3

Describe Foreign Material Contamination

Answer 3

• Foreign products are introduced into a drug
  
  • Foreign ingredients or products
  • Impurities in the ingredients
  • Endotoxins
  • Particulate matter
  • Micro-organisms
  • Products or substances other than product manufactured

Question 4

Describe Fibre as a Foreign Material Contaminant

Answer 4

• Usually identified using polarised light microscopy
• Variety fibres found within same sample = more serious contamination issue

Question 5

Describe Glass Particles as a Foreign Material Contaminant

Answer 5

• Can be generated by fracture of the vial neck or opening, from external sources such as other vials, glassware and lighting and from delamination of the inner vial surface
• Sink rapidly to the bottom of the vial when the liquid is agitated

Question 6

Describe Silicone as a Foreign Material Contaminant

Answer 6

• Used as a lubricant for rubber stoppers and plungers
• ‘Sloughs off’ - ends up in product
• Can interact with protein based drugs or active ingredients producing particles
• Silicone oil = oil droplets = hazy appearance

Question 7

Describe the Control of Dust Contamination

Answer 7

• ​Dust is a carrier of microbes and contaminants
• Ambient bacteria are removed by filtration
• Internal bacterial distribution can be controlled by directional air flow and air flushing or dilution

Question 8

How can Product Related Contamination be Prevented?

Answer 8

• Should be protected from light
  
  • Darkened glass, metal containers
• Materials susceptible to oxidation by air or attack by moisture
  
  • Sealed containers
  • Air from containers can be displaced by an inert gas e.g. N
  • Can be prevented by adding suitable antioxidants which are capable of undergoing oxidation as the expense of the substances

Question 9

Describe Drug Counterfeiting

Answer 9

• A pharmaceutical product which is deliberately and fraudulently mislabelled with respect to identity and/or source
• Branded and Generic Products:
  
  • Products with correct or incorrect ingredients
  • Products without active ingredients
  • Products with incorrect quantity of active ingredient
  • Fake packaging

Question 10

Describe Cross Contamination

Answer 10

• Contamination of a starting material, or of a product with another starting material or product

Question 11

What does the risk of accidental cross-contamination arise from?

Answer 11

• The uncontrolled release of dust, gases, vapours, sprays or organisms from materials and products in process
• From residues on equipment and from operators’ clothing
• Things that are more sensitive e.g. injection, parenteral, opthalmics

Question 12

Define Disinfectants

Answer 12

• Process of removing micro-organisms from surface of objects

Question 13

Define Antiseptics

Answer 13

• Destruction or inhibition of micro-organisms on living tissues to limit/prevent harmful effects of infection

Question 14

Define Preservatives

Answer 14

• Limit proliferation of micro-organisms that may be introduced into non-sterile products such as oral and topical

Question 15

Why do we add preservatives?

Answer 15

• Prevent microbial spoilage of product, minimise risk of infection

Question 16

Should preservatives be added?

Answer 16

• Yes: Multidose medication bottles
• Avoid: Younger paediatric patients

Question 17

Which Preservative to use?

Answer 17

• Wide spectrum of antimicrobial activity
• Chemically and physically stable over the shelf-life of product
• Not compromise the quality or performance of product, pack or delivery system
• Low toxicity

Question 18

What factors are the basis for selecting a preservative?

Answer 18

• Effectiveness
• Effect of pH on preservative
• Safety and comfort of patient

Question 19

Describe Effectiveness in terms of the Basis for selecting a preservative

What are the factors that limit effectiveness?

Answer 19

• Require broad spectrum antimicrobial
• Factors that limit effectiveness
  
  • Inactivation due to interaction with container
  • Adsorption onto suspended solids
  • Entrapment of preservative within mielles or surfactants

Question 20

Describe the Effect of pH on Preservatives

Answer 20

• Many preservatives are weak organic acids
• Partition coefficient
  
  • [HA]org: concentration of preservative in organic phase at equilibrium
  • [HA]aq: concentration of preservative in aqueous phase at equilibrium

Question 21

Describe Safety and Comfort of Patient in terms of Preservatives

Answer 21

• Toxicity
• Hypersensitivitiy/irritation to skin
• Odour
• Taste

Question 22

What are the Types of Preservatives?

Answer 22

• Acids and Esters
• Esters of p-hydroxybenzoic acid (parabens)
• Alcohols (aliphatic)
• Alcohols (Arakyl and highly substituted aliphatic)
• Bronopol

Question 23

What are the Main Disadvantages of Acids and Esters as Preservatives?

Answer 23

• Low pKa, most active at pH below 4

Question 24

What are the Advantages and Disadvantages of Esters of p-hydroxybenzoic acid (parabens) as Preservatives?

Answer 24

• Advantages:
  
  • ​Prepared to overcome pH dependence
  • Active against broad spectrum of microorganisms
  • More effective against Gram +ve
• Diadvantages:
  
  • ​Inactivation by non-ionic surfactants
  • Reduced activity against bacteria; especially pseudomonads
  • Limited solubility in water
  • As chain length increases, hydrophobicity increases and antimicrobial activity increases

Question 25

What are the Advantages of Alcohols (aliphatic) as Preservatives?

Answer 25

* Used disinfection and antisepsis * Main advantages: * Volatile = rapid and large reduction of skin flora

Question 26

What are the Disadvantages of Alcohols (Arakyl and Highly Substituted Aliphatic) as Preservatives?

Answer 26

Instable

Question 27

What are the Advantages and Disadvantages of Bronopol as Preservatives?

Answer 27

* **Advantages:** * **​**Water soluble * Broad spectrum * Used @ concentrations \<0.1% = cost effective * Active against Pseudomonas Aeruginosa * Stable in acid media * **Disadvantages:** * **​**Decompose in light and alkaline pH * Forms toxic decomposition products * Formaldehyde * Nitrites - react to form nitrosamines

Question 28

What are the advantages of using a combination of preservatives?

Answer 28

* Can be used in low concentrations * less toxicity * Wide spectrum of activity * Less incidence of resistance

Question 29

Describe Aldehydes as a Preservative What is an example and describe its characteristics

Answer 29

* Especially effective against Gram-Negative Bacteria * E.g. Imidazolindinyl Urea (Biopure 100) * Broad spectrum antibacterial (effective against pseudomonas sp) * Effective over pH range 3-8.5 * Retains activity in presence of proteins and non-ionic surfactants * Highly water soluble * Many types of personal care products

Question 30

What is an example of Quaternary Ammonium Compound as a Preservative? What are its characteristics?

Answer 30

* Benzylkonium Chloride * Ophthalmic Formulations * Toxic effects demonstrated in laboratory and clinical studies * Irritation to cornea