Excipients for Parenterals
Parenteral excipients are substances used in the formulation of injectable drugs. They are an important component of parenteral products as they help to stabilize, solubilize, and enhance the delivery of active pharmaceutical ingredients (APIs) to the patient.
Definitions of Parenteral Excipients
As per the United States Pharmacopeia-National Formulary (USP-NF), a parenteral excipient is defined as “any substance, other than the active ingredient(s), added to a parenteral product.”
Similarly, the European Pharmacopoeia (EP) defines parenteral excipients as “all constituents of a medicinal product, other than the active substance, that are intentionally added to the product with the aim of enhancing its stability, bioavailability or tolerability, or to facilitate its administration.”
Quality Attribute of parenteral Excipients
The quality attributes of excipients are critical since they impact the quality attributes of the final formulations. The excipient attributes for parenteral excipients include:
- Purity: Parenteral excipients must be of high purity, typically meeting compendial standards such as those set by the United States Pharmacopeia (USP), European Pharmacopeia (EP), or Japanese Pharmacopeia (JP).
- Compatibility: Excipients must be compatible with the active ingredient and other excipients in the formulation to prevent any adverse reactions, such as precipitation or degradation.
- Sterility: Excipients must be sterile to prevent microbial growth and contamination in the formulation.
- Stability: Excipients must be stable throughout the shelf-life of the drug product, preventing any degradation or loss of activity of the active ingredient.
- Safety: Excipients must be safe for use in humans and not cause any adverse effects or toxicity.
- Functionality: Excipients must perform their intended function, such as solubilizing or stabilizing the active ingredient, without interfering with its activity.
- Traceability: Excipients must be traceable to their source and manufacturing process to ensure quality and safety.
- Regulatory compliance: Excipients must comply with regulatory requirements in the countries where they are used, such as those set by the U.S. Food and Drug Administration (FDA) or the European Medicines Agency (EMA).
- Consistency: Excipients must be consistent in their physical and chemical properties, ensuring reproducibility of the drug product from batch to batch.
Overall, parenteral excipients must meet high standards of quality and safety to ensure the efficacy and safety of the final drug product.
Parenteral Excipients – See our introduction video
Functional excipients in parenteral formulations
Functional excipients are substances added to pharmaceutical formulations to enhance the performance of the active ingredient or to improve the stability, bioavailability, or pharmacokinetic properties of the formulation. In parenteral formulations, functional excipients play a critical role in ensuring the safety and efficacy of the drug product.
Here are some commonly used functional excipients in parenteral formulations:
- Buffering agents: These agents help to maintain the pH of the formulation, which is critical for the stability and activity of the active ingredient.
- Solubilizing agents: These agents improve the solubility of poorly soluble drugs in the formulation, enhancing their bioavailability.
- Preservatives: These agents prevent microbial growth and contamination in the formulation, helping to maintain the integrity and sterility of the drug product.
- Stabilizers: These agents protect the active ingredient from degradation or oxidation, improving the shelf-life of the drug product.
- Viscosity modifiers: These agents control the viscosity and flow properties of the formulation, which is important for the ease of administration and drug delivery.
- Tonicity adjusters: These agents help to adjust the osmotic pressure of the formulation, which is important for minimizing discomfort at the injection site.
- Complexing agents: These agents form stable complexes with the active ingredient, improving its solubility, stability, and bioavailability.
- Antimicrobial preservatives: These are specific types of preservatives that are used to prevent the growth of microorganisms in the formulation.
- Antioxidants: These agents protect the active ingredient from oxidation, which can cause degradation and loss of activity.
- Chelating agents: These agents bind to metal ions, preventing them from catalyzing the degradation of the active ingredient.
- Suspending agents: These agents help to suspend insoluble particles in the formulation, improving the uniformity and stability of the drug product.
- Surfactants: These agents reduce the surface tension between the formulation and the container, improving the wetting and spreading properties of the drug product.
- Water for injection: This is a highly purified form of water that is used as a solvent or diluent in parenteral formulations.
- Solvents: These are other types of solvents that can be used in parenteral formulations, such as ethanol, propylene glycol, and glycerin. They can improve the solubility and bioavailability of the active ingredient, but they must be chosen carefully to avoid toxicity or other adverse effects.
Excipients used in parenteral formulations
Common parenteral excipients used in pharmaceuticals include:
- Water for Injection (WFI): A purified form of water that is used as a solvent and diluent in parenteral products. It is prepared by distillation or reverse osmosis and is free from pyrogens.
- Sodium Chloride Injection: A sterile solution of sodium chloride in water for injection. It is used as a tonicity adjuster and diluent for parenteral products.
- Lactose: A disaccharide that is used as a bulking agent in freeze-dried parenteral products.
- Mannitol: A sugar alcohol that is used as a bulking agent and tonicity adjuster in injectable products.
USP Monograph Mannitol.
- Polysorbate 80: A nonionic surfactant that is used as an emulsifying agent and solubilizer in parenteral products.
- Propylene Glycol: A solvent that is used as a co-solvent and co-surfactant in parenteral products.
- Benzyl Alcohol: A preservative that is used to prevent microbial growth in multi-dose vials of parenteral products.
- Citric Acid: An organic acid that is used as a pH adjuster in parenteral products.
- Sodium Citrate: A sodium salt of citric acid that is used as a pH adjuster and anticoagulant in parenteral products.
- Glycine: An amino acid that is used as a buffer and stabilizer in parenteral products.
In addition to the above-mentioned excipients, there are several other excipients that are used in parenteral products. These include preservatives, antioxidants, buffers, chelating agents, and viscosity modifiers. It is important to select appropriate excipients based on the specific needs of the drug product to ensure its safety, efficacy, and stability.
Exipients for parenteral Drug Delivery on pharmaexcipients.com in alphabetical order
Parenteral Drug Delivery
Parenteral drug delivery refers to the administration of drugs via injection directly into the body, bypassing the gastrointestinal tract. This method of drug delivery is typically used for drugs that cannot be taken orally or when immediate and precise drug delivery is required.
The United States Pharmacopeia-National Formulary (USP-NF) defines parenteral drug products as “pharmaceutical preparations that are intended for injection through the skin or other external boundary tissue, rather than through the alimentary canal.” Similarly, the European Pharmacopoeia (EP) defines parenteral products as “medicinal products intended for injection, infusion or implantation into the body.”
There are several types of parenteral drug delivery methods, including:
- Intravenous (IV) Injection: This involves injecting the drug directly into a vein, allowing for rapid onset of action. IV injection is typically used for drugs that require immediate effects, such as emergency medications or chemotherapy drugs.
- Intramuscular (IM) Injection: This involves injecting the drug into a muscle, allowing for slower absorption and longer-lasting effects. IM injection is commonly used for vaccines, antibiotics, and hormone therapies.
- Subcutaneous (SC) Injection: This involves injecting the drug into the fatty layer beneath the skin, allowing for slower absorption and longer-lasting effects. SC injection is commonly used for insulin and some vaccines.
- Intradermal (ID) Injection: This involves injecting the drug into the skin, just below the surface, allowing for slow absorption and localized effects. ID injection is commonly used for allergy testing and some vaccines.
The FDA and EMA both require that parenteral drug products be safe, effective, and free from harmful contaminants. To ensure the safety and efficacy of parenteral drug products, strict regulations and guidelines have been established, including requirements for quality control, manufacturing practices, and labeling.
There are advantages and disadvantages of parenteral drug delivery compared to oral dosage forms.
Advantages of parenteral drug delivery:
- Faster onset of action: Parenteral administration allows drugs to be delivered directly into the bloodstream, resulting in a rapid onset of action.
- Higher bioavailability: Parenteral administration bypasses the first-pass metabolism in the liver, which can result in higher bioavailability of the drug.
- Precise dosing: Parenteral administration allows for precise dosing of drugs, which can be critical for drugs with a narrow therapeutic index.
Disadvantages of parenteral drug delivery:
- Increased risk of infection: Parenteral administration requires the use of needles and syringes, which can increase the risk of infection if proper aseptic techniques are not followed.
- Requires trained healthcare professionals: Parenteral administration requires trained healthcare professionals for proper administration, which may not always be available.
- Higher cost: Parenteral administration is typically more expensive than oral administration due to the need for specialized equipment and healthcare professionals.
Parenteral drug delivery may be the preferred method of administration for drugs that cannot be administered orally, such as drugs that are poorly absorbed or metabolized in the gastrointestinal tract or drugs that are rapidly degraded by stomach acid. Parenteral administration may also be preferred for drugs that require rapid onset of action or precise dosing.
Examples of drugs that are commonly administered via parenteral routes include vaccines, antibiotics, insulin, chemotherapy drugs, and emergency medications such as epinephrine for anaphylaxis. However, the choice of drug delivery method ultimately depends on the specific drug, its intended use, and the patient’s individual needs and preferences.