PHC465 – Sterile Pharmaceuticals: Injections & Parenteral Preparations

Question-and-answer flashcards covering definitions, routes, advantages, formulation factors, pharmacopoeial standards, excipients, containers, sterilisation and labelling for sterile parenteral products.

What does the term “parenteral” literally mean?

Outside the intestine (from Greek para = outside, enteron = intestine).

How are parenteral drug products most commonly administered in practice?

By injection.

Give the pharmacopoeial definition of an Injection.

A sterile, pyrogen-free preparation intended to be administered parenterally as a solution, emulsion or suspension.

Why must all parenteral products meet endotoxin limits?

Excess endotoxin can cause fever, hypotension and shock when injected.

State two clinical reasons for choosing a parenteral route.

Rapid action in emergencies; patient cannot take oral medication (unconscious, unco-operative, vomiting, etc.).

Which three common parenteral routes account for most injections?

Intravenous (IV), intramuscular (IM) and subcutaneous (SC).

What angle of needle insertion is used for an IV bolus injection?

15°–20° to the skin.

Maximum recommended single IV infusion bag volume in hospitals

About 1 L (sometimes larger for parenteral nutrition).

Why is the basilic or cephalic vein often chosen for IV access?

They are superficial, easily accessible and have low risk of extravasation.

Typical volume range for a slow IV infusion?

Up to several litres, e.g., 500 mL–1 L per bag.

Maximum volume usually injected SC without causing pain

~1 mL (not more than 2 mL).

Gauge and length of typical SC insulin needle

25–30 G, 5⁄16–5⁄8 inch.

Standard angle for SC injection

45° (occasionally 90° with short needles).

Usual adult IM injection volume limit in the deltoid

≤ 2 mL.

Usual adult IM injection volume limit in the gluteal muscle

≤ 5 mL (practical 4 mL).

Needle gauge commonly used for IM injections

20-22 G.

Where are intradermal (ID) injections placed?

Between the epidermis and dermis.

Typical ID injection volume

Up to 0.2 mL.

Give two diagnostic uses of intradermal injection.

Allergy testing; tuberculin (Mantoux) testing.

Where is an intrathecal injection delivered?

Into cerebrospinal fluid in the subarachnoid space.

Maximum volume usually given intrathecally

Up to 10 mL.

What is an intra-articular injection mainly used for?

Local delivery of anti-inflammatory drugs into joints (e.g., knee).

List the five ‘official’ USP types of injectable products.

Injection, For Injection, Injectable Emulsion, Injectable Suspension, For Injectable Suspension.

Why must injections for multiple dosing contain a preservative?

To inhibit microbial growth after repeated vial punctures.

Name three core general pharmacopoeial tests for parenterals.

Sterility, endotoxin/pyrogen content, particulate matter.

What particulate limits apply to IV injections (example EP)?

Specified maximum numbers of ≥10 µm and ≥25 µm particles per container (exact numeric limits given in monograph).

Why are preservatives prohibited in large-volume infusions?

Toxic amounts would be delivered if whole litre were infused.

Define a crystalloid IV solution and give one example.

Isotonic electrolyte solution that distributes rapidly in extracellular fluid; e.g., 0.9 % sodium chloride (normal saline).

Define a colloid IV solution and give one example.

Gelatinous solution containing large molecules that remain intravascular, exerting oncotic pressure; e.g., albumin, dextran, HES.

Two formulation strategies when a drug is unstable in aqueous solution

Supply as dry powder for reconstitution or formulate as a suspension/ nonaqueous solution.

Most frequently used solvent in large-scale manufacture of injections

Water for Injection (WFI), USP.

Is WFI sterile?

No, but it must be pyrogen-free and used within 24 h before final sterilisation.

Why is ‘Bacteriostatic Water for Injection’ limited to ≤30 mL vials?

It contains antimicrobial agents that would be toxic in large volumes.

Label warning on bacteriostatic water regarding neonates

“NOT FOR USE IN NEONATES” (risk of benzyl alcohol toxicity).

Give two common water-miscible cosolvents used to improve solubility.

Ethanol; propylene glycol (also glycerol).

List four key properties required of a non-aqueous solvent.

Non-toxic at dose, non-irritant, chemically stable, suitable viscosity/boiling point for sterilisation.

Why is nitrogen flushing used during filling of some vials?

To displace oxygen and reduce oxidative degradation of the drug.

Give one water-soluble and one oil-soluble antioxidant for injections.

Ascorbic acid (water); α-tocopherol (oil).

Target physiological pH for most parenteral formulations

≈ 7.4 (but may be adjusted for drug stability).

Name two acidifying and two alkalising agents for pH adjustment.

Acids: hydrochloric, citric acids. Bases: sodium hydroxide, sodium bicarbonate.

Why are tonicity-adjusting agents added?

To make solution isotonic with plasma, minimising pain and haemolysis.

Maximum endotoxin level for Sterile Water for Injection, USP

≤ 0.25 EU/mL.

What glass type is required for most parenteral ampoules and vials?

Type I (borosilicate) glass.

Give one advantage and one disadvantage of glass ampoules.

Advantage: minimal interaction with product, inexpensive; Disadvantage: breakability and risk of glass particle contamination when opened.

Why do multi-dose vials include a rubber septum and a preservative?

Septum allows multiple needle entries; preservative controls microbial contamination introduced during repeats.

Why are collapsible polyolefin infusion bags preferred over PVC?

Lower leaching of plasticisers, greater drug compatibility.

Define sterilisation.

Destruction or removal of all living microorganisms and their spores from a preparation.

Most common terminal sterilisation method for aqueous injections

Autoclaving with saturated steam (moist heat).

What must every sterilised batch pass before release?

A validated sterility test (and endotoxin test where applicable).

List six mandatory label elements for any parenteral container.

Name of preparation; drug amount/strength; route of administration; storage conditions & expiry date; manufacturer/distributor; batch/lot number.

Why must part of a parenteral container remain label-free?

To allow visual inspection of the solution for particles or precipitation.

Give two disadvantages of parenteral therapy.

Requires aseptic technique/trained personnel; irreversible once IV dose administered; higher cost; pain/risk of infection.

Which parenteral route offers 100 % bioavailability?

Intravenous.

How can IM formulations be manipulated to give prolonged release?

Use suspensions, depot oils or biodegradable microspheres to slow absorption.

What is the European Pharmacopoeia stance on visible particles in injections?

Solutions must be clear and free of visible particles; suspensions exempt but not for IV use.

Why is pH 7.4 not always used even though it is physiological?

The drug may be most stable or soluble at a different pH; buffers keep it in that range.

State two key manufacturing area controls for sterile products.

HEPA-filtered air with positive pressure, and operation in classified cleanrooms (e.g., ISO 5 laminar flow hoods).

How is Water for Injection commonly produced?

By distillation or reverse osmosis followed by filtration.

What happens to particulate-containing injection found on visual inspection?

It must be discarded – unsuitable for patient use.

Explain why IV dose differs greatly from oral dose.

IV avoids first-pass metabolism and absorption barriers, so less drug is needed for the same systemic exposure.

Identify one label warning specific to Lidocaine 2 % Injection ampoules.

‘Not for spinal use’ (formulated for infiltration/nerve block/epidural only).

What calculation limit applies to benzyl alcohol as preservative in neonates?

Neonates have limited detoxification; benzyl alcohol must essentially be avoided (linked to ‘gasping syndrome’).