3. ⢠The term derived from Greek word âParaâ
outside & âEnteroneâ 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 doesnât 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 â 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 â for 30 min
⢠121â for 20 min
⢠Hot air oven
⢠160â 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
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