Preparationes Parenteral

Parenteral Definition

• Parenteral preparations are sterile and intended for administration via injection or infusion, or implantation within the human or animal body.

What is Parenteral?

• It can be a solution, emulsion, suspension, concentrate, powder, gel, or implant.
• Includes injection, infusion, or direct implantation into the vascular system, muscle, soft tissue, or anatomical space.
• Large Volume Parenterals (LVP) range from 100 to 1000 mL, while Small Volume Parenterals (SVP) are less than 100 mL.
• Parenterals should be sterile or have low particulate levels.

Reasons for Using Parenterals

• Intravenous (IV) administration bypasses absorption, offering 100% bioavailability.
• Used when the oral route is unavailable, such as when patients cannot swallow.
• May be necessary when a drug isn't absorbed orally or is metabolized in the GI tract/liver.
• Offer an effective and predictable response.
• Provide a rapid effect.
• Allow for delayed, prolonged, controlled, or localized effects.

Advantages of Parenterals

• Suitable for patients unable to swallow.
• Useful when the GI tract is not functioning.
• Can be administered in emergency situations.
• Offer rapid drug release.
• Can provide delayed, prolonged, controlled, or localized effects.
• Do not require water for administration.

Disadvantages of Parenterals

• Reduced patient compliance.
• Can be painful or stressful for the patient.
• Generally expensive to manufacture.
• Stringent requirements for manufacturing.
• Often require professional administration.

Injections

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

Infusions

• Large volume (LVP) infusions range from greater than 100 mL to 1000 mL.
• Always delivered intravenously.
• Usually formulated as sterile solutions or emulsions.
• Typically contain no preservatives and are for single use.

Concentrated Solutions

• Concentrated solutions are prepared for injection.
• Allow for patient-specific doses/volumes.
• Dilution with water for injection or 0.09% w/v sodium chloride is needed.

Powders

• Dry, solid, sterile powders are sealed in their final container.
• Generally unstable in aqueous solution.
• Must be reconstituted/diluted before administration.
• Freeze-dried products are included in this category.

Gels

• Possess enhanced viscosity suited to guarantee a modified release of the active substance at the injection site.
• An example is hyaluronic acid injections for knee pain related to osteoarthritis.

Implants

• Defined as sterile solid preparations that contain one or more active ingredients.
• Provide a release, over an extended period.
• Can be made of titanium, silicone, or polymer.
• Contraceptives are an example.

Routes of Administration

• Intramuscular injections are administered at a 90-degree angle.
• Subcutaneous injections are administered at a 45-degree angle.
• Intravenous injections are administered at a 25-degree angle.
• Intradermal injections are administered at a 10-15-degree angle.

Errors in Administration

• Major area of safety concern.
• Wrong route of administration; IV instead of IM or SC instead of IM.
• An incorrect preparation; diluted in the wrong solvent.
• Administered at the wrong time or outside the required time frame.

Complications in Administration

• Extravasation is the leakage of intravenous medications into the extravascular tissue near the infusion site.
• Air embolism occurs when a blood vessel is blocked with injected air.
• Hypersensitivity is a patient's allergic reaction to medication.
• Thrombosis is blood clot formation
• Phlebitis is vein irritation.

Manufacture - Sterility

• Products must be free from viable microorganisms and pyrogens.
• It bypasses the body’s natural defense mechanisms.
• Clean rooms: Prepared terminally sterilised or aseptically prepared.

Particulates

• Includes microbe-carrying particles (MCP) and inert particles.
• Solutions should be free of visible particles and have low numbers of sub-visible particles.
• Suspensions can have particles but cannot be delivered intravenously, as particles can lodge in capillaries and cause a pulmonary embolism.
• Emulsions should have a droplet size smaller than 3 μm.

Excipients

• These include vehicles, preservatives, antioxidants, pH adjustment buffers, and suspending agents.

Vehicles

• Water is used 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: used for water-insoluble drugs.
• Oils: used in intramuscular injections.

Preservatives

• Inhibit the growth of microorganisms introduced into multi-dose products.
• Co-solvents can also exhibit microbial effects.

Antioxidants

• Oxidation is addressed by "sparaging," displacing oxygen with nitrogen gas.
• Examples include Vitamin C and E, and sulfite salts.
• Hydrolysis: all water must be removed.

pH Adjustment and Buffers

• Plasma and extracellular fluid has a pH of 7.4
• The pH must be between 5.0-9.0 (above 9.0 can cause tissue necrosis, and below 5.0 causes pain/phlebitis).
• Stability and solubility depend on pH.
• Can be adjusted with acidifying or alkalizing agents (e.g., hydrochloric acid).
• Buffers are used to maintain pH.

Suspending Agents

• Ensure the drug is readily and uniformly suspended prior to 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 lower to higher solute concentration across a semi-permeable membrane, creating osmotic pressure.

Hypertonic Solutions

• Have a higher solute concentration and osmotic pressure than blood plasma.
• Cause water to be drawn out of cells by osmosis, leading to shrinking which causes pain.
• Must be diluted before administration to avoid these adverse effects.

Isotonic Solutions

• Have the same solute concentration in the solution and blood plasma.
• Possess the same osmotic pressure; therefore, there is no net water movement.
• A 0.9% sodium chloride solution, often regarded as 'ideal'.

Hypotonic Solutions

• Feature a lower solute concentration and osmotic pressure than blood plasma.
• Cause water to be driven into cells by osmosis, potentially causing cells to burst which is painful.
• Adjustments: Adding sodium chloride, dextrose, or mannitol can quickly restore cell plasma volume (e.g., saline).

Packaging - Ampoules

• Used for small volumes: < 1-10 mL.
• Made of Glass (Type I) or plastic (polyethylene/polypropylene).
• Single-use and unpreserved.

Packaging - Pre-filled Syringes

• Hold small volumes between 0.5 - 20 mL of solution.
• Come in a glass or plastic base.
• Convenient, affordable, accurate, sterile, and safe.

Packaging - Infusion Bags & Bottles

• Typically range in volume from 100-1000 mL.
• Can be glass bottles (Type 1), collapsible plastic bags (PVC), or semi-ridged plastic bottles (polyethylene).
• Include additive ports for additional medications.
• Designed for single use.

Complications: Contamination

• The primary complication to be aware of.
• Can be microbial: bacterial, fungal, or viral in nature.
• Sources of contamination: air, operators, or water.

Particulate Matter

• Types: dust, fibers, metal, rubber, glass, precipitates.
• Sources: environment, packaging, formulation components, or the manufacturing process.