Parentrals

PARENTERALS
PRESENTED BY
P.KALYANI (11AB1R0075)
UNDER THE GUIDANCE OF
Mrs K. PALLAVI M.Pharm
Asst . Professor
VIGNAN PHARMACY COLLEGE
Affiliated to JNTU Kakinada Approved by AICTE, PCI
Vadlamudi, Guntvuigrna nD phisartm. aAcy ncodllehgerapradesh-522213. 1

CONTENTS
• INTRODUCTION
• ROUTE OF ADMINISTRATION
• GENERAL REQUIRMENTS
• PRE-FORMULATION
• ADJUSTMENT OF TONICITY METHODS
• STERILIZATION
• FORMULATION OF PARENTERALS
• PACKAGING
• EVALUATION OF PARENTERALS.
vignan pharmacy college 2

INTRODUCTION
• The term of parenteral is derived from Greek word para meaning beside
and enteron meaning the intestine.
• Thus parenterals administration should include the administration of
drug by any route other than intestine.
• Parenteral products are considered to be those sterile drugs, solutions,
emulsions, suspensions.

DEFINITION
Parenterals are sterile preparations intended for administration
under or through one or more layers of skin or mucous
membranes.

ADVANTAGES
• The parenterals are administration of unconscious
patients.
• Who can not take oral administration.
• They are free from pyrogen.
• Low toxicity as compared to solid dosage forms.
• 100% bioavailability.
• No chance of missing dose.

DISADVANTAGES
• Requirement of aseptic technique in production compounding and
handling of products.
• Requirement of trained personnel for administration.
• Real or psychological pain associated with the injection.
• Highly risky if any mistake at happens any point.
• High cost as compared to solid dosage forms.

ROUTE OF ADMINISTRATION
Intravenous
Intramuscular
Subcutaneous
Intradermal
Other routes

VARIOUS TYPES OF ROUTE OF
ADMINISTRATION

Not more than

Intra arterial injection

Intra cisternal injection

GENERAL REQUIRMENTS
Vehicle
General
requirements
Additives
Containers and
emulsifying agents
Tonicity
contributors

VEHICLE
• Water for injection is the vehicle of first choice. It should be free from
ions and carbohydrates.
• No bacterial contamination.
• Bacteriostatic water for injection is sterile
water for injection containing one or more
bacteriostatic agents.
• Some co-solvents are used from preparation.
• Water missible co solvent include in ethyalcohol,glycerin and
propylenglycol,polyethyleneglycol.

• In addition of solutes should be free from
microbial contamination.
• Using additives various types.
VEHICLE
• Stabilizers ensure the stability of the drug
compound in the preparation.
• Eg: chelating agent like EDTA.
STABILIZERS
WETTING,
SUSPENDING AND
EMULSIFYING
AGENT vignan pharmacy college 16
• Wetting agent to maintain the particle size.
• Eg: Tween80,sorbital,trioleate,etc…
• Suspending agent is acacia, gelatin etc….

•Formulations must be maintain the
intended Ph.
•Eg:Acetone,citrates,phosphates etc…
BUFFERING AGENTS
• Oxygen sensitive drugs so as to avoid
oxidative degradation.
• Eg:Sodiumbisulphate,formaldehyde,
acetone,thiourea and EDTA.
ANTIOXIDANTS
• It is used for prevention of microbes in
multiple packaging.
• Eg:phenol or chlorobutanol, etc…
ANTIMICROBIAL
AGENTS

TONICITY
CONTRIBUTORS
Eg: sodium
chloride,
and borax etc…
Determining the
freezing point of the
solutions.
Parenteral solutions are
required to be isotonic
with blood serum or
other body fluids.

CONTAINERS AND CLOSURES
• Any container for parenteral products should maintain the
integrity of the product.
• Sterile and pyrogen free.
• Should also attractive.
• Should not react with the products.
• Glass, plastic, rubber materials used type-1 glass mainly
used.
• Plastic used in polyethylene, polypropylene.

PREFORMULATION

PREFORMULATION
• Preformulation involves the determination of both physical and
chemical properties of drug with the goal producing a new drug which is
safe stable and efficacious.
• The establish the physicochemical properties of new drug moiety.
• Determine the kinetic profile of new drug.
• Preformulation studies are of various types:
Physicochemical properties of new drug substance.
Stability testing.
Mechanism of drug degradation.
Testing for packaging material

Physicochemical
properties of new drugs
PRE-FORMULATION
Mechanism
of drug
degradation
Test for packaging
material
Stability test

• The first and most important step in
preformulation is determine the molecule
structure and weight.
MOLECULAR
STRUCTURE AND
WEIGHT
• Appearance of colourchange is indicative
of physicochemical instability which may
decrease the shelf life of the product.
COLOUR
• The drug may undergo physical or
chemical changes due to variations of
temperature which may be associate with
loss or gain. The change analyzed by
DTA and DSC.
THERMAL ANALYSIS

SOLUBILITY
• A clear solution for injectable that are to be administered either infusion
or via i.m route mainly depends on solubility.
• Solubility of drug substances can be determined by spectrophotometric
method or from Ph profile.
• Non aqueous solvents like ethyl alcohol, glycerin, polyethylene glycol.
PARTITION CO-EFFICIENT
• It is used to determine the rate and extent of drug absorption.
• They are explained by equation:
P=Co/Cw

TEST FOR STABILITY
LIGHT STABILITY
• Drug solution placed in the petriplate and glass ampoules respectively.
• Drug substance placed in light resistant container such as carbon box
which act as controller.
• The samples are placed and maintain lighting condition such as 500 foot
candles for a period of 4 weeks.
• consider light extremely any changes discolouration, precipitation,
decomposition observe in the sample to consider light sensitive and
require light protection in both solid and liquid form.

MECHANISM OF DRUG DEGRADATION
• It is the most common reaction which
responsible for the degradation of
compounds.Eg:sodium Phenobarbital etc.
HYDROLYSIS
• Oxidation may lead to discolouration of
the parenteral solution.
• Eg:ascorbic acid, adrenaline etc.
OXIDATION
REACTION
• This reaction is commonly observed in
compounds containing carboxylic acid
functional group
DECORBOXYLATION

TESTING FOR PACKAGING COMPONENTS
GLASS
• Powdered glass
test.
• Water attack test.
PLASTIC
• Leakage test
• Collapsibility test
• Clarity of aqueous
test
• transparency
RUBBER
• Penetrability
• Fragmentation
• Self sealbility test
• Extractive test

ADJUSTMENT OF TONICITY METHODS
CRYSCOPIC
METHOD
TONICITY
METHODS
WHITE-VINCET
METHOD
MOLECULAR
CONCENTRATION
NACL
EQUIVALENT
METHOD

PRECAUTIONS FOR ASEPTIC WORK
• The parenteral products are free from microbial contamination
following precautions should be observed in aseptic work.
• Whenever possible a non-touch technique should be used.
• Air disturbance should be maintained.
• Only trained person should be perform aseptic work.
• Whenever contamination is detected the sources should be removed.

Solutions sterilized
by filtration are to be
filled under aseptic
conditions.
Filling consist of a
quantity of the
product measuring
by precision.
Modern days
automatic high speed
filling can fill up to
300 or more
container per min.
FILLING

Prevent the
contamination.
Vials and bottles are
sealed by close and
open with a closures.
Variety of automated
sealing devices are
available today.
SEALING

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32
STERILIZATION
Heat
Sterilization
Filtration
Sterilization
Radiation
Sterilization
Gaseous
Sterilization
Moist heat Dry heat Non ionizing
radiations
Ionization
radiation
Hot air oven Incineration

STERILIZATION
STERILIZATION PROCESS BIOLOGICAL INDICATION
Moist heat sterilization Spores of bacillus
stearothermophillus are killed.
Dry heat sterilization Spores of bacillus purmilus.
Ionization radiation sterilization Spores of bacillus pumilus bacillus
subtilis.
Gaseous sterilization Spores of bacillus subtilis.
Filtration sterilization Spores of serratia marcescens
Spores of brevundimonas diminuta

PARENTERAL PREPARATION AREA

PRODUCTION OF PARENTERALS
 They are various types of parenterals:
 Powder parenterals for injection :-Eg-cefuroxine for injection
 Colloidal solution :-Eg-irondextran
 Injectable suspension :-Eg-methyl prednisolone acetate
 Oily injectable solutions :-dimercaprol injection

PRODUCTION OF PARENTERALS
37
vignan pharmacy college
 General steps involved
Cleaning
Preparation of bulk production
Filtration
Filling of solution in ampoules or vials
sealing
Sterilization and test quality control.

SMALL VOLUME PARENTRALS PREPARATION
 Small volume of parenterals include ampoules of 1ml, 2ml,3ml up to
20ml and vials of 1ml up to 3oml.
 They are administered by various routes
 They most widely used small volume parenterals are various insulin
preparations used for treatment of diabetes mellitus.
 EXAMPLES:-DIGOXIN-Solution it is administered i.v it is used for
cardiotonic.
 Procaine pencilinG :- it is used for treatment of bacterial infection.

LARGE VOLUME PARENTRALS PREPARATION
• Large volume of parenterals contain 100ml and more of injection
solution they are general administered i.v route.
ELECTROLYTES
• Sodium chloride and potassium chloride solutions
NON-ELECTROLYTES
• Dextrose,mannitol solution.
• Large volume of parenterals are provides nutrition.
• Loss of water diarrhea or vomiting in case used.
• When they are unable to consume oral nutrition for longer periods
(3-6days).

POWDER PARENTERALS
• Dry powders are available in the market they are soluble in water for
injection or in other sterile solvent just prior to use.
• Powder Parenterals are suitable for certain formulations which degrade
by hydrolysis.
EXAMPLES
• Penicillin,ampicillin,amoxycillin,etc….

VOLUME OF INJECTION
VOLUMES(ML) EXCESS VOLUMES
(MOBILE PHASE)
EXCESS
VOLUME(VISCOUS
PHASE)
0.5 0.10 0.12
1.0 0.10 0.15
2.0 0.15 0.25
5.0 0.30 0.50
10.0 0.50 0.70
20.0 0.60 0.90
50.01 2% 3%

Air control
FACILITIES
Environmental
control
Surface
disinfection
Personnel traffic control

HEPA FILTER
◊ Hepa filters can remove at least 99.97% of air bone particals 0.3 mm
in diameter.
◊ These are composed of a mat of randomly arranged fibers.
◊ The air space between hepa filter fibers is much greater than 0.3mm.
◊ Smaller pollutants and particles are mainly trapped by one of the
following….
- Interception
- Impaction
- Diffusion

TYPES OF AIR CONTROL SYSTEMS
S.NO CLASS DESCRIPTION PREPARATION
AREA
A Class 100 Particle count in air is not
more than 100 per cubic
foot of 0.5 μ and particle
size.
Sterile and aseptic
area.
B Class 1000 Particle count in air is Not
more than 1000 per cubic
foot of 0.5μ.
Manufacturing
area.
C Class10,000 Particle count in air is not
more than 10,000 per
cubic foot of 0.5μ and
particle size
Package and
storage area

PACKAGING
GLASS
PLASTIC
RUBBER

GLASS
• Glass materials are no water permeation and glass
permeation not react with products.
• Physical property is optically clear rigid so mainly glass
material used.
PLASTIC
• Plastic closures are used for packaging of parenterals
• Examples:-ampoules(single dose) ,vials(multiple dose)
cartridges , automatic index.
RUBBER
• Rubber closures are used for secondary seal that holds the
primary seal in place.
• Aluminum caps are used for parenterals packaging.

QUALITY CONTROL OF
PARENTERAL
PREPARATIONS

LEAKAGE TEST
QUALITY
CONTROL TEST
CLARITY TEST
STERILITY TEST
PYROGEN TEST

LEAKAGE TEST
Take the ampoules or vials containing sample
Invert the ampoules in 1% methylene blue solution
Observe colour of the sample before and after test
If colour change occur leakage present.
If colour change does not occur leakage absent.

MICROSCOPIC
COUNT METHOD
CLARITY
TEST
COULTER
COUNTER
METHOD
LIGHT
OBSTRUCTION
METHOD
VISUAL METHOD

• The ampoules are placed in dark back -
ground observe light particles.
• Light back ground observe dark particles.
VISUAL METHOD
• A measure sample solution is filtered
through membrane filters.
• Particles observe in the microscope under
100x magnification.
MICROSCOPIC
COUNT METHOD
• The particles observe in the solution
cross the light beam by using light beam
instrument.
• The particles measured and counted.
LIGHT
OBSTRUCTIVE
METHOD

Visual inspection light beam

Permissible limits for particulate matter according to I.P
PARTICAL SIZE MAXIMUM NUMBER
OF PARTICALS(ML)
10 50
25 5
50 Nill

• 2

 RESULT
 The test is positive when each rabbit show increase in the temperature
it only 2 of the three rabbits show increase in temperature.
 The test using group of five and test will be positive if the four of the
rabbits show increase the temperature.
 DISADVANTAGES
 Biological variation
 Expensive
 Laborious
 Dose dependent
 Not for antipyretic drugs

LAL BACTERIAL ENDOTOXIN TEST
 The LAL (limulus amebolyte lysate) assay is an vitro assay used to
detect the presence and concentration of bacterial endotoxins in drugs
one biological product.
 Endotoxins which are a type of pyrogen are lipopolysaccharides present
in the cell walls of gram negative bacteria.
 Pyrogens as a class are fever-inducing substances that can be harmful or
even fatel if administered to humans above certain concentrations.
 Water can be a source of pyrogen so it may be important to routinely
monitor water systems using to bacterial endotoxins test.

CRITERIA FOR LIMULUS TEST RESULT
LAL TUBE TEST
SAMPLE/CONTROL
RESULT
1 Negative control
(pyrogen free saline)
Should be -ve
2 Positive control(pyrogen) Should be +ve
3 Positive internal control
(test sample tainted with
exdotoxines)
Should be +ve
4 Test for sample May be +ve or -ve

1. Membrane Filtration
Method

 Parenterals are the most reliable and promising
formulation which avoid first pass metabolism and
provide 100% bioavailability.
6-9 2014

References
1. Sandeep Nema, John D.Ludwing
pharmaceutical dosage forms volume-I
(pg:1-358) and volume-II (pg:-1-56,221-353).
2. Jain Gupta modern dispensing pharmacy (pg:-357-375).
3. Loyd V.Allen, Jr Nicholas G.popovich Howandc.Ansel-
ANSEL’S Pharmaceutical dosage forms and drug delivery
system (pg:-443-540).

References
4. Leon Lachman,Herbert A.lieberman The theory and
practice of industrial pharmacy (pg:-619-6390).
5. Martin’s Physical pharmacy and pharmaceutical sciences
(pg:-634-635).
6. Umang H.Shah,Ashok H.Arabari,Amitkumar baser GPAT
and other competitive examination in pharmacy
(pg:-1.65-1.70)

ACKNOWLEDGEMENT
 Thank you for paying attention.
 I also sincerely thank my guide Mrs.K.PALLAVI madam for the
valuable guidance and support.
 I sincerely thank our principal Dr. P. Srinivasa babu sir for the
constant encouragement.
 A special thanks to seminar committee for giving me this
opportunity.

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