Parenterals: Definition, Usage, Advantages

• Parenteral refers to sterile preparations administered via injection, infusion, or implantation in the human or animal body.

What is a Parenteral?

• It can be a solution, emulsion, suspension, concentrate, powder, gel, or implant.
• Administered through injection, infusion or direct implantation
• Reaches the vascular system, muscles, soft tissue, or anatomical spaces/organs.
• Large Volume Parenterals (LVP) range from 100-1000 mL, while Small Volume Parenterals(SVP) are less than 100 mL.
• Parenterals should be sterile or have a low particulate count.

Why Use Parenterals?

• IV administration bypasses absorption, resulting in 100% bioavailability.
• Used if the oral route is unavailable, such as when the patient cannot swallow.
• For when a drug is not absorbed orally or is metabolized in the GI tract/liver.
• This route provides an effective and predictable response.
• Achieves a rapid effect or provides delayed, prolonged, controlled, or localized effects.

Advantages of Parenterals

• Suitable for patients unable to swallow or with a non-functioning GI tract.
• Beneficial in emergency situations.
• Can result in rapid drug release.
• Enables delayed, prolonged, controlled, or localized effects.
• No need for water administration.

Disadvantages of Parenterals

• Reduced patient compliance.
• Can be painful or stressful for the patient.
• More expensive to manufacture.
• Requires stringent manufacturing requirements.
• Professional administration is required in most instances.

Injections

• Small volume (SVP) injections are less than 100 mL.
• Use sterile solutions, emulsions, or suspensions.
• Include drug excipients in a vehicle.

Infusions

• Large volume infusions (LVP) range from >100mL to 1000mL.
• Delivered intravenously.
• Use sterile solutions or emulsions.
• Typically have no preservatives and are for single use.

Concentrated Solutions

• Concentrated solutions are designed for injection,
• Designed for patient-specific doses/volumes.
• Diluted with water for injection or 0.09% w/v sodium chloride.

Powders

• Dry, solid, sterile powders sealed in their final container.
• Unstable in aqueous solution.
• Reconstituted/diluted before administration.
• Can be freeze-dried products.

Gels

• Gels have enhanced viscosity to ensure a modified release of the active substance at the injection site.
• An example of gels are hyaluronic acid injections for knee pain (osteoarthritis).

Implants

• Implants are sterile solid preparations containing one or more active ingredients.
• Provide a release of the active ingredients over an extended period.
• Commonly made with titanium, silicone, or a polymer.
• Contraceptives are an example.

Routes of Administration

• Intradermal: 10°-15° angle
• Intravenous: 25° angle
• Subcutaneous: 45° angle
• Intramuscular: 90° angle

Errors in Administration

• A common safety concern.
• Administering via the wrong route, such as IV instead of IM or SC instead of IM.
• Using the wrong preparation or diluting in the wrong solvent.
• Timing administration incorrectly, such as outside the required timeframe.

Administration Complications

• Extravasation: leakage of intravenous (IV) medications into the extravascular tissue around the infusion site.
• Air embolism: blood vessel blocked with injected air.
• Hypersensitivity: patient allergy to medication.
• Thrombosis: blood clot.
• Phlebitis: vein irritation.

Manufacture - Sterility

• Products must be free from viable microorganisms and pyrogens.
• Parenterals bypass the body’s natural defense system and barriers, directly entering the bloodstream or body tissue.
• Produced in a clean room, terminally sterilized or aseptically prepared.

Particulates

• Microbe-carrying particles (MCP) and inert particles.
• Solutions: should be free of visible particles and have low numbers of sub-visible particles.
• Suspensions: particles are permitted but should not be delivered intravenously, as they can lodge in capillaries, potentially causing a pulmonary embolism.
• Emulsions: droplet size < 3 µm.

Excipients - Vehicles

• Water for Injection (WFI).
• Co-solvents: aid the solubility of poorly soluble drugs, e.g., ethanol, glycerol.
• Solubilizing agents: aid dissolution.
• Oil in water (o/w) emulsion: for water-insoluble drugs.
• Oils: for intramuscular injections.

Preservatives

• Used to inhibit the growth of microorganisms introduced into multi-dose products.
• Co-solvents can also exhibit a microbial effect.

Antioxidants

• Oxidation "sparging": displacing oxygen with nitrogen gas.
• Antioxidants: Vitamin C and E, sulfite salts.
• Hydrolysis: remove all water.

pH Adjustment and Buffers

• pH of plasma and extracellular fluid is 7.4.
• pH must be between 5.0-9.0 (>9 = tissue necrosis / <5 = pain/phlebitis in tissue).
• Stability and solubility are also pH-dependent.
• Acidifying or alkalizing agents, e.g., hydrochloric acid.
• Buffers maintain pH.

Suspending Agents

• Ensure the drug is readily and uniformly suspended before administration.
• Examples include water-soluble cellulose derivatives.

Tonicity Adjusting Agents

• Injections and infusions should be isotonic with human plasma.
• A 0.9% sodium chloride solution (osmolarity of 286 mmol/L) is isotonic with human plasma (osmolality of 280-285 mmol/kg).
• Osmosis: The movement of water from areas of lower solute concentration to areas of higher solute concentration across a semi-permeable membrane, which creates osmotic pressure.

Hypertonic

• Features include higher solute concentration and higher osmotic pressure than blood plasma, causing water to be drawn out of cells by osmosis, potentially causing cells to shrink and resulting in pain.
• Solutions must be diluted before administration.

Isotonic

• Have ideal, same concentrations of solute in the solution and blood plasma.
• Same osmotic pressure means movement of water.
• Examples: 0.9% sodium chloride solution.

Hypotonic

• Feature lower solute concentration, and lower osmotic pressure than blood plasma, causing water to be drawn into cells by osmosis,which can cause cells to burst (pain).
• Solutions can be treated by adding sodium chloride, dextrose, or mannitol, which can quickly restore cell plasma volume, e.g., saline.

Packaging - Ampoules

• Small volume: <1-10mL.
• Made of glass (Type I) or plastic (polyethylene/polypropylene).
• For single use, and are unpreserved.

Packaging - Pre-filled Syringes

• Small volume: 0.5-20 mL
• Made of glass or plastic-base
• Convenient, affordable, accurate, sterile and safe.

Packaging - Infusion Bags & Bottles

• Volume: 100-1000 mL.
• Made of glass bottles (Type I), collapsible plastic bags (PVC), and semi-rigid plastic bottles (polyethylene).
• Have additive ports and are for single use.

Complications - Contamination

• Microbial: can be bacterial, fungal, or viral
• Source: air, operators, or water

Particulate Matter

• Types: dust, fibers, metal, rubber, glass, precipitates.
• Source: environment, packaging, formulation components, process.