Sterile products

and admixtures
Presented by:
Rameshwar madharia
PE/2013/313
Parenteral
Parenteral refers injectable route of administration.

It derived from Greek words Para (Outside) and

enteron (Intestine).

So it is a route of administration other than the oral

route. This route of administration bypasses the
alimentary canal
 PRIMARY PARENTERAL ROUTES
Routes Usual volume Needle Formulation Types of medication
(mL) commonly used constraints administered

SVP
Sub cutaneous 0.5-2 5/8 in. , Need to be isotonic Insulin, vaccines
23 gauge
Intra muscular 0.5-2 1.5 in. , Can be solutions, Nearly all drug
23 gauge emulsions, oils or classes
suspensions
Isotonic preferably

Intra venous 1-100 Vein puncture Solutions, emulsions Nearly all drug
1.5 in. , and liposomes classes
20-22 gauge

LVP 101 and larger Venoclysis Solutions and some Nearly all drug
(infusion unit) 1.5 in. , emulsions classes
18-19 gauge
S. No. ADVANTAGES DISVANTAGES

1. Quick onset Wrong dose or over dose can be

fatal

2. Vomiting and unconscious Pain at site

patients can take

3. Prolonged action by modified Trained person required

formulation
( Depot)
4. Nutritive fluids (glucose, Expensive
electrolytes) can be given

5. Drugs with poor absorption NECESSITY OF ASEPTIC

or instability from GIT CONDITIONS IN PRODUCTION,
COMPOUNDING AND
ADMINISTRATION
Containers:
1. Glass:
• Highly Resistant Borosilicate Glass
• Treated Soda lime Glass
• Regular Soda Lime Glass
• N.P (Non-parenteral) Glass
Type 4 is not used for parenteral packaging, others
all are used for parenteral packaging.
 2. Plastic:
Plastic containers are used but they face following problems

• Permeation

• Sorption

• Leaching

• Softening

3. Rubber:
To provide closure for multiple dose vials, IV fluid bottles, plugs for disposable syringes
and bulbs for ophthalmic pipettes, rubber is the material of choice.

Problems associated with rubber closures are

• Incompatibility

• Chemical instability

• Physical instability
 Closure:
• Characteristics of Good Pharmaceutical rubbers

• Good ageing qualities

• Satisfactory hardness and elasticity

• Resistance to sterilization conditions

• Impermeable to moisture and air

• Examples:

• Butyl Rubbers

• Natural Rubbers

• Neoprene Rubbers

• Polyisoprene rubbers

• Silicone Rubbers
Intravenous Admixture System
• “Admixture system” refers to sterile IV solutions that
are prepared by using one or more medications or
electrolytes and will be administered via the parenteral
route.
• It requires the measured addition of a medication to a
50 ml or larger bag or bottle of IV fluid.
• It can be provided to the patient in his/her home.
• Many hospitals involved in compounding IV solutions
and medications to outpatient settings.
Methods for safe & effective use of
IV admixture
• Proper training to nurses & pharmacist
• Instruction regarding labeling Information for
stability & compatibility to the hospital pharmacy
dept.
• Information for the formulation skills to the
pharmacist.
 Preparation
Area

Admixture Storage
system Area
SYSTEM
COMPONE
NT

Policies and
Personnel
Procedures
 PROCESSING OF
PARENTERALS
S.No. STEPS

1. Cleaning of containers, closures and equipments

2. Collection of materials

3. Preparation of parenteral products

4. Filtration

5. Filling the preparation in final containers

6. Sealing the containers

7. Sterilization

8. Evaluation of parenteral preparation

9. Labeling and packaging

Formulation of parenteral products
• In the preparation of parenteral products, the following substances are
added to make a stable preparation:
 The active drug
 Vehicles
 Aqueous vehicle (e.g. water for injection, water for injection free from CO2 )
 Non-aqueous vehicle (e.g. Ethyl alcohol, propylene glycol, almond oil)
 Adjuvants
 Solubilizing agents (e.g. Tweens & polysorbates)
 Stabilizers & antioxidants (e.g. thiourea, ascorbic acid, tocopherol)
 Buffering agents (e.g. citric acid, sodium citrate)
 Antibacterial agents (e.g. benzyl alcohol, metacresol, phenol)
 Chelating agents (e.g. EDTA)
 Suspending, emulsifying & wetting agents (e.g. MC, CMC)
 Tonicity factor (e.g. sodium chloride, dextrose)
Production facilities of parenterals
• The production area where the parenteral
preparation are manufactured can be divided into
five sections:
 Clean-up area

 Preparation area

 Aseptic area

 Quarantine area

 Finishing & packaging area

Clean-up area:
 It is not aseptic area.
 All the parenteral products must be free from foreign particles &
microorganism.
 Clean-up area should be withstand moisture, dust & detergent.
 This area should be kept clean so that contaminants may not be carried
out into aseptic area.

Preparation area:
 In this area the ingredients of the parenteral preparation are mixed &
preparation is made for filling operation.
 It is not essentially aseptic area but strict precautions are required to
prevent any contamination from outside.
Aseptic area:
 The parenteral preparations are filtered, filled into final container & sealed
should be in aseptic area.
 The entry of personnel into aseptic area should be limited & through an air
lock.
 Ceiling, wall & floor of that area should be sealed & painted.
 The air in the aseptic area should be free from fibers, dust and
microorganism.
 The High efficiency particulate air filters (HEPA) is used for air.
 UV lamps are fitted in order to maintain sterility.
Quarantine area:
 After filling, sealing & sterilization the parenteral product are held up
in quarantine area.
 Randomly samples were kept foe evaluation.
 The batch or product pass the evaluation tests are transfer in to
finishing or packaging area.
 Finishing & packaging area:
 Parenteral products are properly labelled and packed.
 Properly packing is essential to provide protection against physical
damage.
 The labelled container should be packed in cardboard or plastic
container.
 Ampoules should be packed in partitioned boxes
EVALUATION OF PARENTERAL
PREPARATIONS
• The finished parenteral products are subjected to
the following tests, in order to maintain quality
control:
• A) sterility test
• B)clarity test
• C)leakage test
• D)pyrogen test
• E)assay
A) sterility test

• It is a procedure carried out to detect and conform

absence of any viable form of microbes in or on
pharmacopeia preparation or product.

1) Method of sterility testing

i ) METHOD 1 Membrane filtration method

ii) METHOD 2 Direct inoculation method

Membrane filtration method (METHOD
1):

 Membrane filtration Appropriate for : (advantage)

• Filterable aqueous preparations

• Alcoholic preparations

• Oily preparations

• Preparations miscible with or soluble in aqueous or oily

(solvents with no antimicrobial effect)

 All steps of this procedure are performed aseptically in a

Class 100 Laminar Flow Hood
 Membrane filter 0.45μ porosity

Filter the test solution

After filtration remove the filter

Cut the filter in to two halves

First halves (For Bacteria) Second halves (For Fungi)

Transfer in 100 ml culture media Transfer in 100 ml culture media

(Fluid Thioglycollate medium) (Soyabeans-Casein Digest medium)

Incubate at 30-350 C for not less then 7 days Incubate at 20-250 C for not less then 7 days

Observe the growth in the media Observe the growth in the media
Direct inoculation method (METHOD
2):

 Suitable for samples with small volumes

 volume of the product is not more than 10% of the
volume of the medium
 suitable method for aqueous solutions, oily liquids,
ointments and creams
 Direct inoculation of the culture medium suitable
quantity of the preparation to be examined is
transferred directly into the appropriate culture
medium & incubate for not less than 14 days.
Observation and results
Culture media is examined during and after at the end of incubation. The following
observations are possible:

1) No evidence of growth Pass the test for sterility.

2) There is evidence of growth Re-testing is performed same no. of sample,

volume & media as in original test No evidence of growth Pass
the test for sterility.

3) There is evidence of growth isolate & identify the organism.

Re-testing is performed with twice no. of sample if:

No evidence of growth Pass the test for sterility.

B)clarity test

• Particulate matter is defined as unwanted mobile insoluble

matter other than gas bubble present in the product.

• If the particle size of foreign matter is larger than the size of

R.B.C.. It can block the blood vessel.

• The permit limits of particulate matter as per I.P. are follows:

Methods for monitoring particulate
matter contamination:

1) Visual method
2) Coulter counter method
3) Filtration method
4) Light blockage method
C)leakage test
• The sealed ampoules are subjected to small cracks which
occur due to rapid temperature changes or due to mechanical
shocks.
Filled & sealed ampoules

Dipped in 1% Methylene blue solution

Under negative pressure in vacuum chamber

Vacuum released colored solution enter into the ampoule

Defective sealing

Vials & bottles are not suitable for this test because the sealing
material used is not rigid
Limulus amebocyte lysate [LAL]
test
• Limulus amebocyte lysate [LAL] test another method
for the determination of pyrogenic endotoxins
• In this method the test solution is combined with a cell
lysate from the ameabocyte [blood celels] of horse shoe
crab
• Any endo toxin that might be present will be coagulated
with protien fraction of the ameabocytes and results in
the formation of a gel
• This consider to be simple,rapid and of greater
sensitivity that the rabbit test
E)assay

• Assay is performed according to method given In

the monograph of that parental preperation in the
pharmacopoeia
• Assay is done to check the quantity of medicament
present in the parenteral preperation
 References
• Encyclopedia of pharmaceutical technology by James Swarbrick
pg.no.1266-1299
• Pharmaceutical product development by N.K.JAIN
• Chemical Incompatibility of Parenteral Drug Admixtures; T. J.
Mccarthy; S.A. Medical journal 2
• The theory & pratice of “Industrial Pharmacy” Leon Lachman ,Herbert
A. Liberman.special Indian Edition 2009 Pg. No.693-680.
• Modern Pharmaceutics Fourth Edition, Revised and Expanded,
Edited By G.S.Banker & C.T.Rhodes, Marcel Dekker pg387-389.
• The Science & practice of Pharmacy, By Remington, Vol-01, Edi.21st,
Lippincott Publication, pg-838-840.
Thank You……..