Pharmaceutics · Short notes

Sterile Products: Short Notes & Cheat Sheet

Parenterals, pyrogens, isotonicity, water for injection, ophthalmic products and sterility testing.

Short notes

Read these before you attempt the topic's MCQs.

Sterility is only one requirement. A sterile product can still cause fever if it contains pyrogens.

Parenteral products must be sterile, free of pyrogens and particles, and ideally isotonic and close to physiological pH.
Small-volume parenterals are 100 mL or less; large-volume parenterals are more than 100 mL (e.g. IV fluids) and must not contain preservatives or bacteriostats.
Intrathecal and epidural injections must be preservative-free.
Water for Injection (WFI) is produced by distillation (or an equivalent validated process) and must be pyrogen-free. Sterile WFI is sterilised in its final container.

Pyrogens are fever-causing substances, mainly bacterial endotoxins (lipopolysaccharide from Gram-negative cell walls).
They are heat-stable, pass through bacterial filters and are water-soluble.
They are destroyed by dry heat (e.g. 250 °C for 30 minutes or more), which depyrogenates glassware.
Testing: the rabbit pyrogen test, or the Limulus amoebocyte lysate (LAL) test, which is faster and more sensitive for endotoxins.

Isotonic solutions have the same osmotic pressure as body fluids, equivalent to 0.9% sodium chloride.
Hypotonic solutions make red cells swell and burst (haemolysis); hypertonic solutions make them shrink (crenation).
Methods to adjust tonicity: freezing-point depression (blood freezes at −0.52 °C), sodium chloride equivalents, and the White–Vincent method.
Eye drops should also be isotonic, although the eye tolerates roughly 0.6–2% NaCl equivalent.

Eye drops must be sterile. Multidose bottles contain a preservative such as benzalkonium chloride.
Once opened, multidose eye drops are usually discarded after 4 weeks (28 days).
Sterility testing uses membrane filtration or direct inoculation into media: fluid thioglycollate medium for anaerobes and aerobes, and soybean–casein digest medium for fungi and aerobes.
A sterility test only samples a batch; sterility is really assured by validated processes (the sterility assurance level).

High-yield facts in one place. Cover the right-hand column and test yourself.

Item	Value
Isotonic saline	0.9% NaCl
Isotonic dextrose	5% dextrose
Freezing point of blood / tears	−0.52 °C
Depyrogenation (dry heat)	≥ 250 °C for ≥ 30 min
Large-volume parenteral	> 100 mL; no preservative
Opened eye drops	Discard after 28 days
Sterility assurance level	10⁻⁶

Medium	Detects
Fluid thioglycollate medium	Anaerobic and aerobic bacteria
Soybean–casein digest medium	Fungi and aerobic bacteria
Membrane filtration	Preferred for antibiotics and oils

Pyrogens are 'HFW': Heat-stable, Filterable (pass bacterial filters) and Water-soluble.

Autoclaving sterilises but does not reliably destroy pyrogens; dry heat at high temperature does.
LAL detects only bacterial endotoxins; the rabbit test detects all fever-causing pyrogens.
Large-volume parenterals must not contain preservatives.
Hypotonic solutions cause haemolysis, not crenation.

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