Introduction to Parenteral Preparations

• Parenteral drug products are the dosage forms intended for administration by a route that does not involve the gastrointestinal (GI) tract (thus, parenteral). Most parenteral drug products are injectable dosage forms intended for administration by injection using a syringe and a needle.
• Parenteral preparations are sterile preparations containing one or more active ingredients intended for administration by injection, infusion, or implantation into the body. They are packaged in either single-dose or multidose containers.
• These preparations may be directly administered or may require reconstituting or diluting prior to administration.

5 Main Types of Parenteral Preparations

1. Injection
2. Infusion
3. Powder for Injection
4. Concentrated Solution for Injection
5. Implants

1. Infusions

These parenteral preparations are composed of a sterile aqueous solution with water as its continuous phase. The preparations are free from bacterial endotoxins or pyrogens and are turned isotonic with blood. They do not contain any antimicrobial preservatives.

2. Powder for Injection

These are sterile solid compounds that are distributed in their final volume when the vial or container is shaken to form a clear particle-free solution.

3. Concentrated Solutions for Injections

The concentrated solutions are diluted with water for injection before they are administered through injection or through intravenous infusion.

4. Implants

These solid sterile preparations are implanted in the tissue in order to release the active ingredient for long periods. They are stored in sterile containers individually.

Why are Parenteral Dosage Forms Preferred?

Parenteral dosage forms are preferred for one or more of the following reasons:

• Low oral bioavailability and/or high variability in oral drug absorption.
• Instability of the drug in the GI tract. For example, most protein drugs are highly unstable.
• Rapid onset of drug action is desired.
• Ability to immediately stop drug administration is important. For example, most emergency room medications and anesthetics.
• High degree of flexibility in dosage adjustment with or without real-time patient physiological response is needed. For example, emergency medications such as analgesics, anticancer drugs, and fertility medications.

Unique Characteristics of Parenteral Products

• Must be absolutely sterile.
• Must be free from pyrogenic (endotoxin) contamination.
• Must be free from visible particulate matter.
• Must be isotonic to body fluid.
• Must be stable (chemically, physically, microbiologically) throughout the shelf life.
• Products must be compatible with diluents/additives, delivery systems & other co-administered products.

Types of parenteral dosage forms

Small-volume parenteral versus large-volume parenteral

Injectable parenteral drug products are available as single or multiuse containers in different container–closure systems and volumes. Small-volume parenterals (SVPs) are available in volumes of less than 1 ml, and up to 50 ml. Large-volume parenterals (LVPs) are usually packaged in volumes up to 1000 mL.

NutritionSVPs include both unit-dose and single-dose and multidose containers. Unit dose containers are usually hermetically sealed ampoules that are intended to be discarded after a single injection. Multidose containers, on the other hand, are usually rubber-stoppered and sealed glass vials that are intended for multiple injections. The drug for each injection is withdrawn by inserting the needle through the rubber stopper, which self-seals after the needle is withdrawn.

SVPs for IV injection may not be isotonic because the large volume of blood rapidly dilutes them. However, hypertonic solutions tend to be tissue irritants. The pH of SVPs can also vary from the physiological pH because the blood buffering system rapidly readjusts the pH after a small volume injection. SVPs for single-dose administration may be free of antimicrobial preservatives, but multidose vials usually have the preservatives to ensure sterility over multiple uses over a certain period of time.

Injections versus infusions

Injection and infusion are the predominant methods of parenteral administration. Injection via different routes of administration usually utilizes an SVP. An infusion involves the IV administration of LVP over a prolonged period of time. Infusions are commonly used for fluid replacement, administration of drugs with a short plasma half-life, and/or dilution of a drug immediately before administration.

Formulation of Parenteral Preparation

Parenteral products can be formulated as solutions, suspensions, emulsions, or lyophilized products (solid) for reconstitution immediately before use.

Parenteral preparations may require the use of excipients such as solvents, substances to enhance solubility, suspending agents, buffering agents, substances to make the preparation isotonic with blood, stabilizers or antimicrobial preservatives. The addition of excipients is kept to a minimum.[cite: 1] When excipients are used they do not adversely affect the stability, bioavailability, safety or efficacy of the active ingredient(s),

• Vehicles
• Added Substance

1. Vehicles in Parenteral Preparation/product

• Aqueous Vehicle ( Pharmaceutical water)
• Non-Aqueous Vehicle

Aqueous Vehicle ( Pharmaceutical water)

Non Aqueous Vehicle for parenteral Preparation

– Vegetable origin Oil

• Fixed oil of vegetable origin.
• Should be metabolized in the body
• Should be liquid at room temp.
• Not to be rancid rapid
• Eg. Corn oil, Seasam oil, almond oil, peanut oil, cotton seed oil etc[cite: 1]

Oil subject to test:

• Fatty acid content
• Iodine value
• Saponification value

Non-Aqueous vehilce is used in the preparation of progesterone, testosterone injection, fat soluble vitamin injection.

Lecithin – used as emulsifier agent in Non-Aqueous vehicles.

2. Additive/added substances in Parenteral Sterile Preparation/product

• a. Antimicrobial Agents
• b. Buffers
• c. Anti-oxidants
• d. Tonicity agents
• e. Cryoprotectants & Lyoprotectants

a. Antimicrobial Agents in parenteral sterile product

• Must be added to preparations contained in multiple dose container [30mL & max 10 withdrawal]
• Used to prevent the growth of Microorganism
• E.xample-
  • Phenyl mercuric nitrate 0.002 % [limit 0.01%]
  • Methyl paraben – 0.18%
  • Propyl paraben – 0.02%
  • Benzyl alcohol – 2% – also have local anesthetic property
  • Benzalkanium chloride & benzene thorium chloride – 0.01%
  • Phenol/cresol – 0.5%
  • Chlorobutanol – 0.5%
• Mercurials are not used because of mercury toxicity.
• Product without preservatives must be used immediately (within 3 hrs) after opening the package

b. Buffers in parenteral sterile product

Used to stabilize a solution against chemical-physical degradation that might occur if the pH changes. Eg. Acid salt of citrates, phosphates.

c. Anti-oxidants used in parenteral sterile product

• Sodium bisulfite
• BHT
• Sodium metasulfite
• BHA
• Ascorbic acid
• Tochopherols
• EDTA
• Displaying O2 in above the solution by purging N2 (inert gas)

d. Tonicity agents used in parenteral sterile product

• Used in Parenteral & Ophthalmic products.
• 0.9% w/v NaCl solution Used to adjust tonicity of the solution
• Injectable product to be isotonic with physiological fluids.
• Isotonic preparation- use to minimize pain & tissue irritation at the site of application.
• Eg. Electrolytes,NaCl or mono/disaccharide sugar

e. Cryoprotectant & Lyoprotactant

• Used to protect Bio-pharmaceutical product from adverse effects during freeze-drying processing.
• Eg. – Sugars (Non-reducing)- sucrose, Amino acids- glysine & lysine; Polymer – Liq PEG, dextran; Polyols – mannitol, sorbitol