parenteral product

1. •Part- I
• Compiled By
• Vaibhav Tripathi Dr. Anil K. Sahu
Dr. Deepak K. Dash

2. • INTRODUCTION
• ADVANTAGES/ DISADVANTAGES
• TYPES
• ESSENTIAL REQUIREMENTS
• FORMULATION CONSIDERATION
• ISOTONICITY
• PRODUCTION PROCESS/PROCEDURE

3. • The term derived from Greek word ‛Para’
outside & ‛Enterone’ intestine.
• Parenterals are sterile solutions or
suspension of drug in aqueous or oily
vehicle.
• Parenteral drugs are administered directly
in to the veins, muscles or under the skin ,
or more specialized tissues such as spinal
cord.

4. • Term parenteral used for any drug/fluid
whose delivery doesn’t utilize the
alimentary canal for entering in to the body
tissues.
• So it is a route of administration other than
the oral route. This route of administration
bypasses the alimentary canal
• Parenteral routes of administration usually
have a more rapid onset of action than
other routes of administration.

5. • Advantages
• The IV route is the fastest method for
delivering systemic drugs. preferred
administration in an emergency situation
• It can provide fluids, electrolytes, and
nutrition. patients who cannot take food or
have serious problems with the GI tract
• It provides higher concentration of drug to
bloodstream or tissues. advantageous in
serious bacterial infection.

6. • IV infusion provides a continuous amount
of needed medication.
• infusion rate can be adjusted to provide
more or less medication as the situation
dictates
• Drug action can be prolonged by modifying
the formulation.

7. • Useful for patients who cannot take drugs
orally
• Useful for drugs that require a rapid onset
of action
• Useful for emergency situations
• Useful for providing sustained drug
delivery (implants, i.m. depot injections)
• Can be used for self-delivery of drugs
(subcutaneous)

8. • Useful for drugs that are inactivated in the
GIT or susceptible to first-pass
• Useful for injection of drugs directly into a
tissue (targeted drug delivery)
• Useful for delivering fluids, electrolytes, or
nutrients

9. • Disadvantages
• Impossible to retrieve if adverse reaction
occurs
• More expensive and costly to produce.
• Potential for infection at the site of
injection,
• thrombophlebitis, fluid overload, air
embolism,sepsis
• Psychological distress by the patient

10. • Disadvantages
• Require specialized equipment, devices,
and techniques to prepare and administer
drugs.
• Potential for pain upon injection
• Potential for tissue damage upon injection
• Risk of needle stick injuries and exposure
to blood-borne pathogens by health care
worker.

11. • Disadvantages
• Increased morbidity associated with long-
term vascular access devices.
• Disposal of needles, syringes, and other
infusion devices requires special
consideration

12. • Types
1. Small volume parenterals (SVP)
• An injection that is packed in containers
labeled as containing 100 ml or less.
2. Large volume parenterals (LVP)
• LVP are parenterals designed to provide :-
• Fluid, Calories (dextrose solution ),
Electrolytes, Combination of these with API
• Volume 101- 1000 ml

13. • Types
• Injection:
• Prepared by dissolving API with other
suitable additives in water for injection /
non- aqueous solvents.
• Infusion:
• Composed of sterile aqueous solution.
Free from microbes. It is an example of
LVP

14. • Types
• Powder for injection:
• To overcome the intrinsic instability of
the drug. Marketed in powder form. It
should be reconstituted before use.
• Conc. Solution for injection:
• Conc. API solution is diluted with water
for injection and administered via IV
infusion/ injection

15. • Types
• PERITONEAL DIALYSIS SOLUTION:
• Such solutions are Infused continuously into
abdominal cavity, bathing peritoneum & are
then continuously withdrawn.
• These are used to remove toxic substances
from body.
• To aid & accelerate excretion normal.
• To treat acute renal insufficiency.

16. • Types
• IRRIGATING SOLUTIONS:
• To irrigate ,flush, & aid in cleaning body
activities & wounds.
• Certain IV solution ( normal saline ) may be
used as irrigating solution , but solution
designed as irrigating solution should not be
used parenterally.
• IMPLANTS:
• API is implanted in the tissue for prolong

17. • Essential Requirements
• Stability : chemical & physical stability or
parenteral preparations must be maintained
throughout shelf life
• Sterility: aseptic environment must be
maintained during preparation &
administration in order to prevent microbial
contamination.
• Specific gravity: this parameter must be
taken in consideration specially in case of
intra spinal injection. Density must be kept in

18. • Essential Requirements
• Free from Pyrogens: parenteral products
must be free from toxins & Pyrogens,
because a contaminated product causes
elevation in body temperature after
application.
• Free from foreign particles: product must be
free from dust particles to avoid embolism
• Isotonicity: product must be isotonic with the
blood plasma
• Chemical purity: chemical composition must

19. • Formulation Consideration
• Formulation involves the blending of one or
more ingredients with API to enhance :-
• Convenience
• Acceptability
• Effectiveness of formulation
• A thorough information about the additives
including its physico- chemical & biological
nature must be known before formulating an
injection

20. • Formulation Consideration
I. Vehicles
II. Adjuvants
1. Solubilizing agents
2. Stabilizers
3. Buffering agents
4. Anti bacterial agents
5. Chelating agents
6. Suspending/ emulsifying & wetting agents

21. • Formulation Consideration
• Aqueous vehicle : water for injection, water
for inj. free from CO2
• Non-aqueous vehicle: Ethyl alcohol,
propylene glycol, almond oil
• Solubilizing agents : Tweens & polysorbates
• Stabilizers: To protect the formulation from
oxidation

22. • Formulation Consideration
• Stabilizers: Reducing agents Ascorbic acid,
Sodium bisulfite 0.01% Thiourea
• Blocking agents Tocopherol
• Buffering agent: Added to maintain pH.
• To stabilize a solution from chemical
degradation.
• Citrate and acetate buffer, Sodium benzoate
and benzoic acid, Sodium tartarate and
tartaric acid Phosphate buffer.

23. • Formulation Consideration
• Anti bacterial agent: To prevent
microorganism growth
• Limited concentration of agents are used.
• Phenyl mercuric nitrate and thiomersol
0.01%.
• Benzethonium chloride & benzalkonium
chloride 0.01%. Phenol & cresol 0.05%.
• Chlorobutanol 0.05%.

24. • Formulation Consideration
• Tonicity agents: Need isotonic solution to
avoid destruction of red blood cells, irritation,
and tissue damage
• More important for large volumes, rapidly
administered and extravascular injections
• Reduces the pain on injection
• NaCl & KCl, Dextrose
• Mannitol & Sorbitol

25. • Importance of Isotonicity
• Osmotic pressure plays a crucial role in
determining the isotonicity of a solution.
• Osmosis is the movement of solvent from
lower solute conc. To higher solute conc.
• Osmotic pressure ∝ no. of solute units
• Isotonicity is determined by investigating the
conc. Of solute at which the cells remain in
their normal size & shape

26. • Importance of Isotonicity
• This operation is become significant &
mandatory while formulating parenteral
preparations.
• Standard for tonicity :
0.9% NaCl Isotonic
More than 0.9%
NaCl
Hypertonic
Less than 0.9%
NaCl
Hypotonic

27. • Importance of Isotonicity for
Parenterals
• Isotonicity adjustment helps to reduce pain in
areas near nerve endings.
• NaCl, glycerin & lactose are usually
employed in parenteral preparations for this
purpose.
• Tonicity adjusters are generally mixed at last
phase to the formulation
• In case of IV approximate isotonicity is
desirable.

28. • Importance of Isotonicity for
Parenterals
• In case of subcutaneous, isotonicity
adjustment is usually not essential because
the medicament is depot into fatty acid &
move into systemic circulation by simple
diffusion.
• IM injection should be slightly hypertonic to
facilitate rapid & better absorption.
• Diagnostic injections must be isotonic to
avoid false reading data.

29. • Importance of Isotonicity for
Parenterals
• Intra-thecal injection must be isotonic since
the volume of CSF is about 60-80 ml only.
• Hence Para-tonic solution may cause serious
adverse complications.
• Hemolytic method is used to determine the
isotonicity.
• Isotonicity can be adjusted by two ways:

30. • Importance of Isotonicity for
Parenterals
• By reducing the concentration of ingredients
(if acceptable)
• OR
• By diluting the preparation with the aid of
tonicity adjuster
• Isotonicity also helps to determine the
capacity of various route of injection

31. • Importance of Isotonicity for
ParenteralsSubcutaneous 0.52- 2 ml
Muscular 0.5- 2 ml
LVP 1- 1000 ml
Intra arterial 2- 20 ml
Intra articular 2- 20 ml
Intra-thecal 1- 4 ml
Intra pleural 2- 30 ml
Intra-cardial 0.2- 1 ml
Intra- dermal 0.05 ml

32. • Production Procedure/ Processing
1. Cleaning of containers, closures &
equipments
2. Collection of materials
3. Preparation of parenteral products
4. Filtration
5. Filling the preparation in final container

33. • Production Procedure/ Processing
7. Sterilization
8. Evaluation of the parenteral preparation
9. Labeling & packaging
SOP must be followed strictly throughout each
& every phase in order to avoid contamination

34. • Production Procedure/ Processing
1. Cleaning of containers, closures &
equipments:
• Thoroughly cleaned with detergents with tap
water/ distilled water finally rinsed with water
for injection.
• Rubber closures are washed with 0.5% sod.
pyrophosphate in water.
• Sterilized by Dry or Moist heat

35. • Production Procedure/ Processing
2. Collection of materials:
All raw material of preparation should be
collected from warehouse. Water for injection
should be Pyrogens free.
3. Preparation of parenteral products:
The parenteral preparation must be prepared in
aseptic conditions.
The ingredients are accurately weighed
separately and dissolved in vehicle as per SOP.

36. • Production Procedure/ Processing
4. Filtration:
The parenteral preparation must be filtered by
bacteria proof filter such as filter candle,
membrane filter, sintered glass filter.
• Anti microbial agent is added at this stage (if
needed)
• 5. Filling the preparation in final container:
• The filling operation is carried out under
strict aseptic precautions.

37. • Production Procedure/ Processing
5. Filling the preparation in final container:
• The filling operation is carried out under
strict aseptic condition.
• Filling can be done either manually using
hypodermic needle or by automatic filling
machines, likewise in case of sterile powder
• Container should be kept empty below the
neck to avoid cracking/ staining at the time of
sealing

38. • Production Procedure/ Processing
6. Sealing the container:
• Sealing should be done immediate after filling
in aseptic environment.
• Ampoules (single dose) are sealed in the
flame / machines
• Vials(multi dose) & infusion bottles are
sealed with rubber closures (manually/
mechanically)

39. • Production Procedure/ Processing
7. Sterilization:
• Sterilization is done immediately after
sealing.
• For thermo-stable substances the parenteral
products are sterilized by autoclaving
method at different temp. & pressure.
• Heat sensitive or moisture sensitive material
are sterilized by exposure to ethylene oxide
or propylene oxide gas .

40. • Production Procedure/ Processing
7. Sterilization:
• Autoclaving
• 115- 116 ℃ for 30 min
• 121℃ for 20 min
• Hot air oven
• 160℃ for 2 hours
• Radiation (0.3 M rad)

41. • Production Procedure/ Processing
• 8. Evaluation of the parenteral preparation:
• The following tests are performed in order to
maintain quality control:
1. Sterility test
2. Pyrogen test
3. Clarity test
4. Leakage test
5. Assay

42. • Production Procedure/ Processing
9. Labeling & packaging:

43. 1. Pharmaceutical product development by N
K Jain.
2. Theory and practice of industrial pharmacy
by Lachman and Leiberman.
3. Industrial Pharmacy: A Comprehensive
Approach by D.K. Tripathi