Parenteral Product: Pharmaceutics
- Parenteral drug products are the dosage forms intended for administration by a route that does not involve the gastrointestinal (GI) tract (thus, parenteral). Most of the parenteral drug products are injectable dosage forms that are 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.
- PPs may directly administer or may require to constituting or diluting prior to administration.
- There are five main types of Parenteral Preparation
- Injection
- Infusion
- Powder for Injection
- Conc. solution for Injection
- Implants
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.
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.
Concentrated Solutions for Injections
The concentrated solutions are diluted with water for injection before they are administered through injection or through intravenous infusion.
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.
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, emer-gency medications such as analgesics, anticancer drugs, and fertility medications.
Unique characteristics of Parenteral Preparation/product
- Must be sterile
- Must be free from pyrogenic (endotoxin) contamination
- Must be free from visible particulate matter
- 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.
SVPs 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. 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)
Find more about types of pharmaceutical water….
Potable water / Drinking water (500 CFU)
| Type of Water | Description (As per Indian Pharmacopoeia) |
|---|---|
| Purified water CFU – 100 | -Prepared by distillation reverse osmosis & the same time Ion-exchange. -Used as a solvent in all pharmaceutical preparation except parenteral sterile preparation. -Also used for all tests & assays of the IP, unless otherwise specified -Hand washing (In the sterile production) |
| WFI CFU-10/ml pH 5-7 | -Pyrogen free only ((not more than 0.25 IU of endotoxin per ml) -Used as a solvent in parenteral preparation Note: it is not intended to be sterile but should comply with the test for a limit of Endotoxin (Pyrosen free). i.e it is pyrogen-free but not sterilized as per IP. -Not contain an added substance |
| SWFI content provided by ThePharmapedia.com | – Sterilised & packed in a single-dose glass container of type I & II; maximum. of 1 (one) Litre capacity. i.e both pyrogen-free and sterilized – Used as a solvent for powder or Injection. -Not contain an added substance |
| BWFI notes by The Pharmapedia | -Sterile WFI contains one or more suitable Bacteriostatic agents & packed in a single or multiple-dose glass container & Maximum 30 mL capacity. -Contain added substance |
| Water BET(bacterial endotoxin test) | it is WFI (Sterilised) & free from an endotoxin – used in the test for Bacterial Endotoxin (Pyrogen) Test. |
| Highly purified water | High Purity water is a Distilled water filtered through 0.45 m membrane & Conductivity not more than 0.15 S/cm @ 25 degrees centigrade. |
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
- Oil subject to test:
- 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
Click here for all additives used in Pharmaceutical
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
MCQs- Formulation of Parenteral Sterile Preparation
1. What is the main requirement for formulations intended for parenteral administration?
a) High viscosity
b) Sterility
c) Sweet taste
d) Colorful appearance
Answer: b) Sterility
2. Which of the following is NOT a route for parenteral administration?
a) Intravenous
b) Oral
c) Intramuscular
d) Subcutaneous
Answer: b) Oral
3. Parenteral formulations must be free from:
a) Microorganisms
b) Preservatives
c) Excipients
d) Water
Answer: a) Microorganisms
4. What type of containers are commonly used for parenteral products?
a) Plastic bottles
b) Amber glass vials
c) Paper cartons
d) Cardboard boxes
Answer: b) Amber glass vials
5. Which technique is primarily used to prepare sterile parenteral products?
a) Filtration
b) Milling
c) Lyophilization
d) Aseptic processing
Answer: d) Aseptic processing
6. What is the key reason to avoid pyrogens in parenteral formulations?
a) To prevent visual cloudiness
b) To prevent fever in patients
c) To maintain pH
d) To enhance shelf life
Answer: b) To prevent fever in patients
7. Which of the following is used to remove microorganisms in sterile filtration?
a) 0.22 micron filter
b) 1 micron filter
c) 5 micron filter
d) 10 micron filter
Answer: a) 0.22 micron filter
8. Parenteral formulations are generally isotonic to avoid:
a) Pain at injection site
b) Color change
c) Freezing
d) Evaporation
Answer: a) Pain at injection site
9. Which pharmaceutical dosage form is designed for parenteral administration?
a) Tablet
b) Suspension
c) Injectable solution
d) Capsule
Answer: c) Injectable solution
10. Pyrogens are typically detected by which test?
a) Sterility test
b) USP rabbit test (Pyrogen test)
c) Dissolution test
d) pH test
Answer: b) USP rabbit test (Pyrogen test)
11. What does ‘aseptic filling’ refer to?
a) Filling under sterile conditions
b) Filling with preservatives
c) Filling in cleanroom after sterilization
d) Manual filling
Answer: a) Filling under sterile conditions
12. Which of the following is a critical quality control test for parenteral products?
a) Viscosity test
b) Particle size analysis
c) Sterility test
d) Dissolution test
Answer: c) Sterility test
13. Which of the following excipients stabilizes parenteral formulations?
a) Preservatives
b) Buffers
c) Fillers
d) Diluents
Answer: b) Buffers
14. Which is a common solvent used in parenteral formulations?
a) Ethanol
b) Water for Injection (WFI)
c) Acetone
d) Benzene
Answer: b) Water for Injection (WFI)
15. Which parenteral route offers the fastest drug onset?
a) Intramuscular
b) Subcutaneous
c) Intravenous
d) Intradermal
Answer: c) Intravenous
16. Which is NOT a characteristic of an ideal parenteral formulation?
a) Pyrogen-free
b) Sterile
c) Stable
d) High particulate content
Answer: d) High particulate content
17. What is the purpose of lyophilization in parenteral drug formulation?
a) Liquid sterilization
b) Increasing drug solubility
c) Freeze-drying to improve stability
d) Enhancing color
Answer: c) Freeze-drying to improve stability
18. The term ‘endotoxin’ refers to:
a) A type of excipient
b) Pyrogenic substances from bacterial cell walls
c) Sterilizing agent
d) Injectable drug
Answer: b) Pyrogenic substances from bacterial cell walls
19. Which iso-osmotic agent is frequently used in parenteral formulations?
a) Sodium chloride
b) Sucrose
c) Talc
d) Starch
Answer: a) Sodium chloride
20. What is the USP limit for particulate matter in parenteral solutions?
a) No limit
b) Strict limits on number and size of particles
c) Only color limits apply
d) Limits on viscosity
Answer: b) Strict limits on number and size of particles