sterile vs non-sterile products

what is product spoilage?

-              Breakdown of the active

-              Breakdown of the formulation

-              Reduced acceptability

-              Degradation of preservative

what are the sources for contamination?

-              Raw materials

-              Premises and environment 

-              Processing

-              Personnel

what are the types of sterile and non-sterile products?

-              Aseptically prepared

-              Terminally sterilised

-              Microbiologically vulnerable non-sterile products

-              All other products

-              Decreasing GMP requirements as you go down

what are the formulation factors affecting microbial content?

-              Water content

-              Nutritional value

-              pH

-              osmotic pressure

-              surface tension

-              oxygen tension

-              storage

what is sterility?

-              the complete absence of organisms

o   Must be absolute

o   Sterile is used for a product

what are the basic axioms?

o   All living organisms should be excluded, removed or destroyed with the highest level of probability

o   SAL has no meaning in the context of aseptic processing

o   Aseptic processing is not a method of sterilisation

o   Whenever possible, sterile products should be terminally sterilised

what does preserving of pharmaceuticals provide protection against?

o   Residual contamination not excluded by GMP

o   Contamination introduced during use

o   Not to cover the bad manufacturing practice

what types of products are preserved?

o   Not self-preserved

o   Preparations in multidose containers

o   Aqueous preparations

o   Non-terminally sterilised products

what considerations should be taking when selecting preservatives?

o   Types of formulation

o   Ingredients

o   Physiochemical properties

o   Route of administration

how can use of a broad spectrum affect preservative activity?

§  eg bronopol

§  However, many show limited activity

how can formulation pH affect preservative activity?

§  Activity of some antimicrobials pH dependent

§  Benzoic and sorbic acids pKa = 4.2-5

§  Active in unionised form so, is only used in pH at 3-6

how can use of phenolics affect preservative activity?

§  pKa:

§  Phenol – 9.98

§  Cresol – 10.08

§  Chlorocresol – 10.08

§  Methylparabens – 8.5

§  These are only affected by pH above pH 9

what are cationic preservatives?

§  Eg chlorohexidine, benzalkonium chloride

§  Inactive below pH 4-5

what are the incompatibilities with surface active agents?

·      Phenols and acids neutralised by cationic surface-active agents

·      Chlorhexidine and benzalkonium chloride neutralised by anionic surface-active agents

what is solubilisation/micellar systems?

·      Preservative is solubilised above the critical micelle concentration (CMC), leading to a reduction in preservative in the aqueous phase

·      Increasing Tween 80 means that parabens must be increased to ensure adequate activity

o   But concentration of parabens in aqueous phase remains constant

how can solids be surface active agents?

·      Active drug, thickening agents or suspending agents

·      Preservatives become adsorbed to the particle surface, and reduces aqueous concentration

o   Eg chlorhexidine - kaolin

o   Eg methylparabens - talc

o   Eg benzalkonium chloride – penicillin

how can the manufacturing environment be controlled to prevent contamination?

·       Facility design & validation: Ensuring clean rooms, air filters, and sterile equipment. 

·       Environmental monitoring: Checking air, water, and surfaces for microbes. 

·       Personnel hygiene & gowning: Workers wear gloves, masks, and sterile clothing. 

Equipment cleaning & sterility