Parenteral drug delivery

1. PARENTERAL
PRODUCTS

2. Definitions related to the topic:
Parenteral Products
Sterilization & Sterile Product
Pyrogen
SVP
LVP
Light Resistant Containers
Well closed containers
Tightly closed containers
Single dose container
Multiple dose container
Hermetically sealed container

3. PARENTERALS
para: outside
enteron: intestine (i.e. beside the intestine)
These are the preparations which are given
other than oral routes.
Injections:
These are
Sterile,
Pyrogen free preparations intended to be
administered parenterally (outside
alimentary tract).

4. DEFINITION
Parenteral preparation or injectables are the
sterile solutions or suspensions of drug in
aqueous or oily vehicles meant for introduction
into the body by means of an injection under or
through one or more layers of the skin or mucous
membrane.

5. •Based on types of packaging
1)Single dose units: ampoules, infusions and
prefilled disposable syringes
2)Multiple dose units: multiple dose vials
•Based on the production and control
a)Small volume parenterals: volume < 100 ml
b)Large volume parenterals: volume ≥ 100 ml
Classification of parenteral preparations

6. •Based on clinical use
a)Solutions for irrigation
b)Ophthalmic solution
c)Dialysis solution
d)Diagnostic agent
e)Allergenic extracts
f)Implants
•Based on physical state of product
a)Sterile solutions
b)Sterile suspensions
c)Sterile emulsions
d)Sterile solids

7. Small volume parenterals:

Volume of these parenterals varies from fractions of
Milli liter to several hundred milliliters i.e. 1ml to 500ml
Example: Injections :- Furosemide, Heparin, Cimetidine,
Iron dextran etc
Large volume parenterals:
Volume of these parenterals varies from 500ml and above.
They are administered as single dose injections at a slow rate.
Example: Infusion Fluids, Total parenteral nutrition solutions,
patient controlled anlgesia, dialysis fluids etc.

8. Why Parenteral?
Parenteral Route Is Used bcoz
1) Rapid action
2) Oral route can not be used
3) Not effective except as injection
4) Many new drugs particularly those derived
from new development in biotechnologically
can only be given by parenteral coz they are
inactivated in GIT if given orally.
5) New drugs require to maintain potency &
specificity sodium that they are given by
parenteral.

9. Advantages:
Quick onset of action
Suitable for the drugs which are not administered by
oral route
Useful for unconscious or vomiting patients.
Duration of action can be prolonged by modifying
formulation.
Suitable for nutritive like glucose & electrolyte.
Suitable for the drugs which are inactivated in GIT or
HCl (GI fluid)

10. Disadvantages:
Once injected cannot be controlled (retreat)
Injections may cause pain at the site of injection
Only trained person is required
If given by wrong route, difficult to control adverse
effect
Difficult to save patient if overdose
Sensitivity or allergic reaction at the site of injection
Requires strict control of sterility & non pyrogenicity
than other formulation.

11. Necessities of Parenteral preparations:
Sterility (must)
Pyrogen (must)
Free from particulate matter (must)
Clarity (must)
Stability (must)
Isotonicity (should)
Solvents or vehicles used must meet special purity and
other standards.
 Restrictions on buffers, stabilizers, antimicrobial
preservative. Do not use coloring agents.
Must be prepared under aseptic conditions.
Specific and high quality packaging.

12. Parental Routes of Administration:
Most Common: 1. Subcutaneous (SC; SQ ;Sub Q)
2. Intramuscular (IM)
3. Intravenous (IV)
Others: 4. Intra-arterial (IA)
5. Intrathecal
6. Intraarticular
7. Intrapleural
8. Intracardial
9. Intradermal (Diagnostic)

13. Routes of Parenteral Administration
Intradermal
Intramuscular
Intravenous Subcutaneous
Dermis
Intra arterial
Vein
Artery
Muscle
Epidermis
Subcutaneous
tissue

14. Subcutaneous (SC; SQ ;Sub Q):
The injection is given under the skin
Need to be isotonic
Upto 2 ml is given
Using ½ to 1 inch 23 gauge needle or smaller needle
Given:
Vaccines
Insulin
Scopolamine
Epinephrine

15. Intramuscular (IM):
Striated muscle fibre
0.5 to 2 ml sometimes upto 4 ml
1 to 1.5 inch & 19 to 22 gauge needle is used
Preferably isotonic
Principle sites:
Gluteal (buttocks)
Deltoid (upper arms)
Vastus lateralis (lateral thigh)
Given:
Solutions
Emulsions
Oils
Suspension

16. Intravenous (IV):
Into the vein
1 to 1000 ml
1 inch ,19 to 20 gauge needle with injection rate
1ml/ 10 sec. for volume upto 5 ml & 1 ml/ 20 sec.
for volume more than 5 ml.
Given:
Aqueous solutions
Hydro alcoholic solutions
Emulsions
Liposome

17. IV infusion of large volume fluids (100- 1000
ml) has become increasingly popular. This
technique is called as Venoclysis.
This is used to supply electrolytes & nutrients
to restore blood volume & to prevent tissue
dehydration.
Combination of parenteral dosage forms for
administration as a unit product is known as
an IV admixture.
Lactated Ringer Injection USP
NaCl Injection USP (0.9 %)– (replenish fluid &
electrolyte)
Dextrose Injection USP (fluid & electrolyte)

18. Intra-arterial (IA):
Direct into the artery
2 to 20 ml
20 to 22 gauge
Solutions & emulsions can be administered
Given:
Radio opaque media
Antineoplastic
Antibiotics

19. Intrathecal:
Also called intra-spinal
Directly given into the spinal cord
1 to 4 ml
24 to 28 gauge
Must be isotonic
Given:
LA
Analgesics
Neuroleptics

20. Intraarticular:
Given directly into the joints
2 to 20 ml
5 inch 22 gauge
Must be isotonic
Given:
Morphine
LA
Steroids
NSAID’s
Antibiotics

21. Intrapleural:
Given directly into the pleural cavity or lung
Used for fluid withdrawal
2 to 30 ml
2 to 5 inch, 16 to 22 gauge needle
Given:
LA
Narcotics
Chemotherapeutic agents

22. Intracardial:
Directly given into the heart
0.2 to 1 ml
5 inch , 22 gauge needle
Given:
Cadiotonics
Calcium salts as a calcium channel blockers

23. Intradermal:
Also called as diagnostic testing
0.05 ml
½ inch, 25 to 26 gauge needle
Should be isotonic
Given:
Diagnostic agents

24. Official Types of Injections:
1. Solutions of Medicinal
Example: Codeine Phosphate Injection
Insulin Injection
2. Dry solids or liquid concentrate does not contain
diluents etc.
Example: Sterile Ampicillin Sodium
3. If diluents present, referred to as.....for injection
Example: Methicillin Sodium for injection

25. Parenteral drugs are formulated as solutions, suspensions,
emulsions, liposomes, microspheres, nanosystems and
powders to be reconstituted as solutions.
Formulation mainly consists of two components
•Contents
•Container
Formulation principles:

26. CONTENTS
A.Vehicles
1.Water
1.water for injection
2.sterile water for injection
3. bacteriostatic water for injection
2. Non-aqueous vehicles
water miscible vehicles
water immiscible vehicles

27. 1.Solutes or added substances
1.Antimicrobial preservatives
2.Antioxidants
3.Solubilizers, wetting agents or emulsifiers
4.Buffers
5.Bulking substances or tonicity modifiers
6.Suspending agents
7.Chelating agents
8.Stabilizers
9.Local anaesthetics
10.Antioxidants
2.reducing agents
3.blocking agents
4.synergists
5.chelating agents

28. a.It is most frequently used in the large scale manufacturer of
injections.
b.Water of suitable quality for compounding and rinsing product
contact surfaces may be prepared either by distillation method
or reverse osmosis, to separate adequately various liquid, gas,
and solid contaminants and undissociated substances such as
pyrogens present in the absence of ions from water.
c.It is not required to be sterilized and pyrogen free.
d.It is intended to be used within 24 hours after collection.
e.The water should be collected in sterile and pyrogen free
containers.
f.It contains total solid contents not more than 1 mg/100 ml.
VEHICLES
Water for injection:

29. Sterile water for injection:
a.It must be pyrogen free but an allowable endotoxin level is not
more than 0.25 USP endotoxins units per milliliter.
b.It may not contain any added substance like antimicrobial agent.
c.It is packed in single dose containers not larger than 1 liter.
d.This water is intended to be used as solvent, vehicle or diluent for
already sterilized and packaged injectable medications.
e.It is mainly used for reconstitution of multiple antibiotics.
f.It contains more slightly more total solid contents than the water
for injection because of the leaching of solids from the glass lined
tanks during sterilization.

30. a.It is sterile water for injection containing one or more
suitable antimicrobial agents.
b.It is packaged in prefilled syringes or in vials
containing not more than 30 ml of the water.
c.It is used as a sterile vehicle in the preparation of
small volumes of the injectable preparations ( in large
volumes, excessive and toxic amounts of
bacteriostatic agents such as benzyl alcohol may
cause gasping syndrome(multiorgan failure )).
d.Presence of bacteriostatic agent in small volumes may
provide flexibility for multiple-dose vials.
e.This water is specifically labeled as per the USP
requirements as “NOT FOR USE IN NEONATES”.
Bacteriostatic water for injection:

31. 1.Total solids content- a gravimetric evaluation of the
dissociated and undissociated organic and inorganic
substances present in the water.
2.Electrolytic measurement of the conductivity- immersing
electrodes in the water and measuring the specific
conductance, a measurement that depends on the ionic
content of water.
Conductance may be expressed by the meter scale as
1.conductivity in micromhos
2.resistance in megohms
3.ionic content in ppm of sodium chloride
Water for injection should not have a conductivity of more
than 1 micromho, 1 megohm and approximately 0.1 ppm
sodium chloride
Quality tests for Water for Injection:

32. a)These are mainly used to eliminate water entirely or impart from the
vehicle, primarily because of the solubility factors or hydrolytic reactions.
b)It must be non-irritating, non-toxic or non-sensitizing and it must not
exert an adverse effect on the ingredients of the formulation.
c)It must not exert a pharmacological activity of its own and it may not
adversely affect the activity of the medicinal agent.
d)It physical and chemical stability at various pH levels
e)It has sufficient viscosity which must be such as to allow ease of injection.
f)It has Fluidity, which must be maintained over a fairly wide temperature
range
g)It has a Boiling point, which should be sufficiently high to permit heat
sterilization, miscibility with body fluids and low vapor pressure to avoid
problems during heat sterilization.
Non-aqueous vehicles

33. Two types of solvents are mainly used in combination with water are
1.water miscible solvents
2.water immiscible solvents
Water miscible solvents Water immiscible solvents
Dioxolanes Fixed oils
Dimethylacetamide corn oil
N-(β-hydroxyethyl)-lactamide cottonseed oil
Butylene glycol peanut oil
Polyethylene glycol 400 and 600 sesame oil
Propylene glycol Ethyl oleate
Glycerin Isopropyl myristate
Ethylalcohol Benzyl benzoate

34. a.The most commonly used solvents are Polyethylene glycol,
Propylene glycol and fixed oils.
b.Ethyl alcohol (40% ethanol with water) is particularly used in
the preparation of solutions of cardiac glycosides.
c.Glycols are mainly used in the solutions of barbiturates, certain
alkaloids and certain antibiotics.
d.The fixed oils must be of vegetable origin so that they will be
1.metabolized
2.liquid at room temperature
3.not become rancid readily
4.clear when cooled to 10°C to ensure the stability and clarity
of the injectable product during refrigeration.
5.Not contain mineral oil or paraffin, as these are not
absorbed by body tissues.
6.Having saponification value between 185 and 200 and an
iodine value between 79 and 141

35. I)All substances added to the preparation must improve its quality.
II)An added substance may
·Increase and maintain drug solubility. Examples include
complexing agents and surface active agents.
1.Complexing agents include cyclodextrins, mainly Capsitol.
2.Surface active agents include :
polyoxyethylene sorbitan monolaurate (Tween 20) and
polyoxyethylene sorbitan monooleate (Tween 80).
2. Provide patient comfort by reducing pain and tissue irritation.
Examples are
Tonicity modifiers such as sodium chloride, dextrose and glycerin.
3. Enhance the chemical stability of a solution. Examples are
antioxidants, inert
gases, chelating agents and buffers.

Solutes or added substances:

36. 4. Enhance the chemical and physical stability of a freeze-
dried product. Examples
are cryoprotectants and lyoprotectants.
5. Enhance the physical stability of proteins by
minimizing self aggregation or
interfacial induced aggregation. Examples include
surfactants.
6. Minimize protein interaction with inert surfaces
such as glass, rubber and plastic
by adding competitive binders such as albumin and
surface active agents to the
preparation.

37. 1.Protect a preparation against the
growth of micro organisms. Examples
includes
preservatives.
1.Sustaining or controlling the drug
release by using controlled release
polymers.
2.Maintaining the drug in a
suspension dosage form by using the
suspending agents includes polymers
and surface active agents.
3.Maintaining the drug in an
emulsified dosage form by using the
emulsifying agents includes
amphiphilic polymers and surface
active agents.
4.Useful in the preparation of
liposomes by using hydrated
phospholipids.

38. 1.Solubility
2.Melting point
3.Polymorphism
4.Surface characteristics
5.Hygroscopicity
6.Partition coefficient
7.Dissolution
8.Bulk density and powder flow
properties
9.Wetting
PREFORMULATION FACTORS

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