Introduction
History
Why parenteral?
Necessary condition of parenteral
advantages/ disadvantages
Methods of preparation
Quality control
Packaging
Types of parenteral products
Routes of administration
advantages/ disadvantages
conclusion
Kailash vilegave
A detailed study on every aspects of parenteral :- introduction, preformulation factors, essential requirements, vehicles and additives, isotonicity, production procedure, facilities, and controls, container and closure selection and finally the quality control evaluation of parenterals.
A detailed study on every aspects of parenteral :- introduction, preformulation factors, essential requirements, vehicles and additives, isotonicity, production procedure, facilities, and controls, container and closure selection and finally the quality control evaluation of parenterals.
University Institute of Pharmaceutical Sciences is a flag bearer of excellence in Pharmaceutical education and research in the country. Here is another initiative to make study material available to everyone worldwide. Based on the new PCI guidelines and syllabus here we have a presentation dealing with the types of parenteral formulation including the types of parenteral route for administration along withcomponents of parenteral formulation.
Thank you for reading.
Hope it was of help to you.
UIPS,PU team
This pdf contain notes on STERILE DOSAGE FORM (PARENTRA), This notes is specilly used for D. pharm, B. Pharm & M. Pharm Students and respected faculties
These defects can cause serious injury and harm. When this occurs, you should speak with our product liability attorneys in Denver. You may have a viable claim to file a product liability lawsuit against the negligent manufacturer.Capsules are solid dosage forms in which the drug substance is enclosed within either a hard or soft soluble shell. Generally the shells are formed from gelatin. The capsule may be regarded as “container” drug delivery system, which provides a tasteless/odorless dosage form without the need of a secondary coating step, as may be required for tablets.Capsules are one of the essential components of the pharmaceutical sector. They are mainly used to hold dry powder or little pellets of medication and are made using specific machinery and techniques. The capsule's production method entails pharmaceutically active ingredients, additives, and a cover. Every pharmaceutical business understands capsule manufacturing takes time, and the reason is the critical measures.
University Institute of Pharmaceutical Sciences is a flag bearer of excellence in Pharmaceutical education and research in the country. Here is another initiative to make study material available to everyone worldwide. Based on the new PCI guidelines and syllabus here we have a presentation dealing with the types of parenteral formulation including the types of parenteral route for administration along withcomponents of parenteral formulation.
Thank you for reading.
Hope it was of help to you.
UIPS,PU team
This pdf contain notes on STERILE DOSAGE FORM (PARENTRA), This notes is specilly used for D. pharm, B. Pharm & M. Pharm Students and respected faculties
These defects can cause serious injury and harm. When this occurs, you should speak with our product liability attorneys in Denver. You may have a viable claim to file a product liability lawsuit against the negligent manufacturer.Capsules are solid dosage forms in which the drug substance is enclosed within either a hard or soft soluble shell. Generally the shells are formed from gelatin. The capsule may be regarded as “container” drug delivery system, which provides a tasteless/odorless dosage form without the need of a secondary coating step, as may be required for tablets.Capsules are one of the essential components of the pharmaceutical sector. They are mainly used to hold dry powder or little pellets of medication and are made using specific machinery and techniques. The capsule's production method entails pharmaceutically active ingredients, additives, and a cover. Every pharmaceutical business understands capsule manufacturing takes time, and the reason is the critical measures.
Introduction
Routes of administration of parenteral dosage form
Types of parenteral preparation
General requirements for parenteral dosage form
Formulation of parenteral preparations
Containers and closures used
Processing of parenteral preparations
Evaluation of parenteral preparations
Labeling and packaging
Production facilities
Preparation of iv fluids and admixtures
Sterlity testing
Particulate matter monitoring
Faculty seal packaging
Definition and classification of parenteral products, formulation considerations, vehicles and
additives, containers, manufacturing techniques, raw materials and machines, quality control of
parenteral products.
Drugs may be administered by various routes. The choice of the route in a given patient depends on the tissue or organ to be treated, the characteristics of the drug and urgency of the situation, etc. Knowledge of the advantages and disadvantages of the different routes of administration is essential. The routes can be broadly divided into Enteral, Parenteral, and Local.
UNIT – V : HUMAN PHYSIOLOGY
CHAPTER 20: LOCOMOTION AND MOVEMENT
Types of movement- ciliary, fiagellar, muscular; Skeletal muscle- contractile proteins and musclecontraction; Skeletal system and its functions (To be dealt with the relevant practical of Practical syllabus); Joints; Disorders of muscular and skeletal system-Myasthenia gravis, Tetany, Muscular dystrophy, Arthritis, Osteoporosis, Gout.
UNIT – V : HUMAN PHYSIOLOGY
CHAPTER 17 : BREATHING AND EXCHANGE OF GASES part 1
Human Respiratory System The Mechanism of Breathing Transport of Oxygen,
Regulation of Respiration
Chapter 17 breathing & exchange of gases (repaired) (2)Kailash Vilegave
UNIT – V : HUMAN PHYSIOLOGYCHAPTER 17 : BREATHING AND EXCHANGE OF GASES
Respiratory organs in animals (recall only); Respiratory system in humans; Mechanism of breathingand its regulation in humans-Exchange of gases, transport of gases and regulation of respiration Respiratory volumes; Disorders related to respiration-Asthma, Emphysema, Occupational respiratory disorders.
UNIT – IV : PLANT PHYSIOLOGY
CHAPTER 14 : RESPIRATION IN PLANTS.
Exchange gases; Cellular respiration-glycolysis, fermentation (anaerobic), TCA cycle and electron transport system (aerobic); Energy relations-Number of ATP molecules generated; Amphibolic pathways; Respiratory quotient.
Kingdom Plantae presented by Vrushali Gharat to Mr. Kailash vilegaveKailash Vilegave
Classification Of Kingdom Plantae, Classification Of Kingdom Plantae, Economic importance Algae.
Ulothrix
Reproduction
Mosses and Liverwort
life cycle of all plants.
Osmotic drug delivery system by Mr. kailash vilegaveKailash Vilegave
INTRODUCTION
ADVANTAGES OF OSMOTIC DRUG DELIVERY SYSTEM
DISADVANTAGES OF OSMOTIC DRUG DELIVERY SYSTEM
REPORTED CASES REGARDING LIMITATIONS AND ADVERSE EFFECTS OF OSMOTIC DRUG DELIVERY SYSTEM
PRINCIPLE OF OSMOSIS
BASIC COMPONENTS OF OSMOTIC PUMP
2024.06.01 Introducing a competency framework for languag learning materials ...Sandy Millin
http://sandymillin.wordpress.com/iateflwebinar2024
Published classroom materials form the basis of syllabuses, drive teacher professional development, and have a potentially huge influence on learners, teachers and education systems. All teachers also create their own materials, whether a few sentences on a blackboard, a highly-structured fully-realised online course, or anything in between. Despite this, the knowledge and skills needed to create effective language learning materials are rarely part of teacher training, and are mostly learnt by trial and error.
Knowledge and skills frameworks, generally called competency frameworks, for ELT teachers, trainers and managers have existed for a few years now. However, until I created one for my MA dissertation, there wasn’t one drawing together what we need to know and do to be able to effectively produce language learning materials.
This webinar will introduce you to my framework, highlighting the key competencies I identified from my research. It will also show how anybody involved in language teaching (any language, not just English!), teacher training, managing schools or developing language learning materials can benefit from using the framework.
Ethnobotany and Ethnopharmacology:
Ethnobotany in herbal drug evaluation,
Impact of Ethnobotany in traditional medicine,
New development in herbals,
Bio-prospecting tools for drug discovery,
Role of Ethnopharmacology in drug evaluation,
Reverse Pharmacology.
Synthetic Fiber Construction in lab .pptxPavel ( NSTU)
Synthetic fiber production is a fascinating and complex field that blends chemistry, engineering, and environmental science. By understanding these aspects, students can gain a comprehensive view of synthetic fiber production, its impact on society and the environment, and the potential for future innovations. Synthetic fibers play a crucial role in modern society, impacting various aspects of daily life, industry, and the environment. ynthetic fibers are integral to modern life, offering a range of benefits from cost-effectiveness and versatility to innovative applications and performance characteristics. While they pose environmental challenges, ongoing research and development aim to create more sustainable and eco-friendly alternatives. Understanding the importance of synthetic fibers helps in appreciating their role in the economy, industry, and daily life, while also emphasizing the need for sustainable practices and innovation.
The Indian economy is classified into different sectors to simplify the analysis and understanding of economic activities. For Class 10, it's essential to grasp the sectors of the Indian economy, understand their characteristics, and recognize their importance. This guide will provide detailed notes on the Sectors of the Indian Economy Class 10, using specific long-tail keywords to enhance comprehension.
For more information, visit-www.vavaclasses.com
Unit 8 - Information and Communication Technology (Paper I).pdfThiyagu K
This slides describes the basic concepts of ICT, basics of Email, Emerging Technology and Digital Initiatives in Education. This presentations aligns with the UGC Paper I syllabus.
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What is the purpose of the Sabbath Law in the Torah. It is interesting to compare how the context of the law shifts from Exodus to Deuteronomy. Who gets to rest, and why?
Read| The latest issue of The Challenger is here! We are thrilled to announce that our school paper has qualified for the NATIONAL SCHOOLS PRESS CONFERENCE (NSPC) 2024. Thank you for your unwavering support and trust. Dive into the stories that made us stand out!
The French Revolution, which began in 1789, was a period of radical social and political upheaval in France. It marked the decline of absolute monarchies, the rise of secular and democratic republics, and the eventual rise of Napoleon Bonaparte. This revolutionary period is crucial in understanding the transition from feudalism to modernity in Europe.
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Model Attribute Check Company Auto PropertyCeline George
In Odoo, the multi-company feature allows you to manage multiple companies within a single Odoo database instance. Each company can have its own configurations while still sharing common resources such as products, customers, and suppliers.
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Bills have a main role in point of sale procedure. It will help to track sales, handling payments and giving receipts to customers. Bill splitting also has an important role in POS. For example, If some friends come together for dinner and if they want to divide the bill then it is possible by POS bill splitting. This slide will show how to split bills in odoo 17 POS.
2. Mr. Kailash Vilegave 2
• Introduction
• History
Why parenteral?
Necessary condition of parenteral
• advantages/ disadvantages
• Methods of preparation
• Quality control
• Packaging
• Types of parenteral products
• Routes of administration
• advantages/ disadvantages
• conclusion
3. History:
Mr. Kailash Vilegave 3
1657: first recorded injection in animals- SirChristopher
Wren
1855: first subcutaneous injection of drugs using hypodermic
needles - Dr.Alexander wood
1920:proof of microbial growth resulting in infections
- Dr. Florence Seibert
1926: inclusion in the national formulary
1931: commercial intravenous solution(Baxter)
1946:organization of parenteral drug association
1965:development of total parenteral nutrition
5. Mr. Kailash Vilegave 5
Necessities of parenteralpreparations:
• Sterility (must)
• Free from pyrogen (must)
• Free from particulate
matter
• Clarity (must)
• Stability (must)
Isotonicity (should)
Solvents and vehicles used
must meet special purity and
other standard
Do not use coloring agents
Must be prepared under
aseptic conditions
Specific and highquality
packaging
6. DEFINATION:
Mr. Kailash Vilegave 6
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
Pyrogens, fever-producing substances, primarily
lipopolysaccharide product of metabolism of microorganism;
they may be soluble, insoluble, or colloid.
7. Advantages of the Parenteral Route
Mr. Kailash Vilegave 7
T h e IV route is the fastest method for delivering systemicdrugs
preferred administration in an emergencysituation
I t can provide fluids, electrolytes, and nutrition.
patients who cannot take food or have serious problems withthe
GI tract
I t provides higher concentration of drug to bloodstream or
tissues
advantageous in serious bacterial infection.
I V infusion provides a continuous amount of needed medication
infusion rate can beadjusted.
t o provide more or less medication as the situation dictates
Drug action can be prolonged by modifying the formulation.
8. Mr. Kailash Vilegave 8
Advantages of Parenteral Administration
1. Useful for patients who cannot take drugs orally
2. Useful for drugs that require a rapid onset of action
(primarily iv admin)
3. Useful for emergency situations
4. Useful for providing sustained drug delivery (implants, im
depot injections)
5. Can be used for self-delivery of drugs (subcutaneous)
6. Useful for drugs that are inactivated in the GIT or
susceptible to first-pass
7. Useful for injection of drugs directly into a tissue (targeted
drug delivery)
8. Useful for delivering fluids, electrolytes, or nutrients
(TPN) Useful for providing precise drug delivery by iv
injection or infusion utilizing pharmacokinetic techniques
9. Can be done in hospitals, ambulatory infusion centers,
and home health care
9. Disadvantages of the Parenteral Route
Mr. Kailash Vilegave 9
Traumatic injury from the insertion of needle
Potential forintroducing:
Toxic agents
Microbes
Pyrogens
Impossible to retrieve if adverse reactionoccurs
injected directly into thebody
Correct syringe, needle, and technique must beused
Rotation of injection sites with long-termuse
prevents scarring and other skinchanges
can influence drugabsorption
10. Mr. Kailash Vilegave 10
Disadvantages of Parenteral Administration
1. More expensive and costly to produce.
2. Potential for infection at the site of injection,
thrombophlebitis, fluid overload, air embolism,
extravasation, sepsis
3. Psychological distress by the patient
4. Require specialized equipment, devices, and techniques to
prepare and administer drugs.
5. Potential for pain upon injection
6. Potential for tissue damage upon injection
7. Risk of needle stick injuries and exposure to blood-borne
pathogens by health care worker.
8. Increased morbidity associated with long-term vascular
access devices.
9. Disposal of needles, syringes, and other infusion devices
requires special consideration.
11. Routes of Administration of parenteral
products
Mr. Kailash Vilegave 11
Various types of route of administration of parenteral products are:
Subcutaneous (Hypodermis) injection
Intramuscular injection
Intravenous injection
Intradermal injection
Intra-arterial injection
Intracardiac injection
Intrathecal injection
Intracisternal injection
Peridural injection
Intra- articular injection
5
12. Subcutaneous Injections
Mr. Kailash Vilegave 12
• Administer medications below the skin into the subcutaneous fat
outside of the upper arm
top of the thigh
lower portion of each side of the abdomen
not into grossly adipose, hardened, inflamed, or swollen tissue
• Often have a longer onset of action and a longer duration of action
compared with IM or IV injection
Given at a 45-degreeangle
25- or 26-gauge needle, 3/8 to5/8
inch length
N o more then 1.5 ml should be
injected into the site
t o avoid pressure on sensory nerves
causing pain and discomfort
13. Intramuscular Injections
Mr. Kailash Vilegave 13
Care must be taken with deep IM injections to avoid hitting a
vein, artery, or nerve
I n adults, IM injections are given into upper, outer portion of the
gluteus maximus
large muscle on either side of thebuttocks
Fo r children and some adults, IM injections are given into the
deltoid muscles of the shoulders
• Typical needle is 22- 25 gauge ½- to 1-inch needle
• IM injections are administered at a 900 angle
volume limited to less than 3 ml
14. Intravenous Injections or Infusions
Mr. Kailash Vilegave 14
Fast-acting route because the drug goes directly intothe
bloodstream
often used in the emergency department and in criticalcare
areas
Commonly used
for fluid and electrolytereplacement
t o provide necessary nutrition to the patient who is
critically ill
• Intravenous (IV) injections are
administered at a 15- to 20-degree
angle
15. Intra-arterial injection
The inaction are given directly in to the artery
Intracardiac injection
These are given into the heart muscle or
ventricle at the time of emergency only.
Intrathecal injection
These are given into the subachonoid space the
surround the spinal cord. This route is used for
spinal anesthesia.
Mr. Kailash Vilegave 15
16. Intracisternal injection
These are given in b/w first & second cervical nerve.
Used for CSF for diagnosticpurpose.
Peridural injection
These are given in b/w the dura matter & inner
aspect of vertebra.
Used for giving spinal anesthesia.
Intra- articular injection
These are given into the articulating ends of bones
in a joint.
Used for lubricating the joints.
Intracerebral injection
These are given into the cerebrum.
Mr. Kailash Vilegave 16
17. Official types of injections
Mr. Kailash Vilegave 17
Injection: Liquid preparation of drug substance or drug
solution e.g. insulin injection USP.
Fo r injection: Dry solid that upon addition of suitable vehicles
yield solutions confirming in all respect to the requirements to
the injection. e.g. Cefuroxime injection USP.
Injectable emulsions: Liquid preparation of drug substance
dispersed in a suitable emulsion medium. e.g. Propofol USP.
Injectable suspension: Liquid preparation of solid suspended
in a suitable medium. e.g. Methyl Prednisolone Acetate
Suspension USP.
Fo r injectable suspension: Dry solid that upon addition of
suitable vehicle yields preparation confirming in all respect
to the requirements for Injectable suspension.
e.g. Imipenem
11
18. General requirements of parenteral preparations
Mr. Kailash Vilegave 18
Stability
Sterility
Free from Pyrogens
Free from foreign particles
Isotonicity
Specific gravity
Chemical purity
Clarity (must)
Solvents and vehicles used must meet special
purity and other standard
Do not use coloring agents
Must be prepared under aseptic conditions
Specific and high quality packaging
19. Formulation of parenteralpro ducts
Mr. Kailash Vilegave 19
wing In the preparation of parenteral products, the follo
substances are added to make a stable preparation:
The active drug
Vehicles
Aqueous vehicle (e.g.water for injection, water for inj. 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)
20. Processing of parenteral preparation
Mr. Kailash Vilegave 20
Following steps are involved in the processing of
parenteral preparation:
1) Cleaning of containers, closures & equipments
2) Collection of materials
3) Preparation of parenteral products
4) Filtration
5) Filling the preparation in final container
6) Sealing the container
7) Sterilization
8) Evaluation of the parenteral preparation
9) Labeling & packaging
21. 1. Cleaning of containers, closures & equipments: Thoroughly cleaned with
detergents with tap water distilled water finally rinsed
with water for injection.
Mr. Kailash Vilegave 21
Rubber closures are washed with 0.5% sod. pyrophosphate in water.
2. Collection of materials: All raw material of preparation should be collect
from warehouse after accurate weighed.
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 method of preparation to be followed.
4. Filtration: The parenteral preparation must be filtered by
ba0c5t/0e2/r1i7aproof filter suH.cPh.IRaisshi,RfaimltPearrajculaindle, membranefilter.
15
22. 5. Filling the preparation in final container: The filling
operation is carried out under strict aseptic precautions.
6. Sealing the container: Sealing should be done immediate after
filling in aseptic environment.
7. Sterilization: For thermostable 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 .
8. Evaluation of the parenteral preparation: The following tests
are performed in order to maintain quality control:
1. Sterility test
4. Pyrogen test
2. Clarity test 3. Leakage test
5. Assay
9. Labeling & packaging.Mr. Kailash Vilegave 22
23. Evaluation of Parenteral
products
Mr. Kailash Vilegave 23
Sterility testing
Particulate matter monitoring or Clarity Test
Faulty seal packaging or leakage test
Pyrogen testing:
Rabbit Test
LAL Test
MAT
Assay or drug content uniformity
24. Sterility testing
Mr. Kailash Vilegave 24
• DEFINITION:
• Sterility Testing: It is a procedure carried out to detect and
conform absence of any viable form of microbes in or on
pharmacopeial preparation or product.
• PRINCIPLE : If the microorganism are present in the product can
be indicated by a turbidity in the clear medium.
• OBJECTIVE OF STERILITY TESTING:
For validation of sterilizationprocess.
To check presence of microorganisms in preparation which are
sterile.
05/0T2/1o7 prevent issuHe.P.IoRfishciRoanmtPaaramjuliinatedproduct in market.
18
25. STEPS INVOLVED IN STERILITY TETESTING
Mr. Kailash Vilegave 25
1) Sampling
2) Selection of the quantity of the product to be used
3) Method of sterility testing
i ) METHOD 1 Membrane filtration method
ii) METHOD 2 Direct inoculation method
1) Observation and interpretation Must be carried out under
aseptic condition.
H.P.I Rishi Ram Parajuli05/02/17 19
26. Sampling
Mr. Kailash Vilegave 26H.P.I Rishi Ram Parajuli
• The sample must be representative of the whole of the bulk
material & a lot of final containers.
• MAINLY FOLLOWED BY TWO RULES:
A fixed percentage of the final container are selected.
A fixed number of container are taken independent of the lot or
batch size.
According to Indian Pharmacopoeia following guidelines for
determining the minimum number of items are:
05/02/17 20
27. Method of sterility testing
Mr. Kailash Vilegave 27
Membrane filtration method (METHOD 1):
Membrane filtration Appropriate for : (advantage)
Filterable aqueouspreparations
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 Laminar
Flow Hood
05/02/17 H.P.I Rishi Ram Parajuli 21
28. Membrane filter 0.45μ porosity
Mr. Kailash Vilegave 28
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
(Fluid Thioglycollate medium)
Incubate at 30-350 C for not less then 7 days
Transfer in 100 ml culture media
(Soyabeans-Casein Digest medium)
Incubate at 20-250 C for not less then 7 days
05O/0b2s/1e7rvethe growth in the media Observe the growth in the med22
ia
29. 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
an creams
Direct inoculation of the culture
medium suitable quantity of the
appropriate culture medium
preparation to be examinedis
transferred directly into the
&
incubate for not less than 14 days.
H.P.I Rishi Ram Parajuli
Direct inoculation method (METHOD 2):
Mr. Kailash Vilegave 2905/02/17 23
30. Observation and results
Mr. Kailash Vilegave 30
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(preserved) 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.
Same as in preserved fail .Diff Re-testing is performed
with twice no. of sample if:
No evidence of growth Pass the test for sterility.
T05h/02e/1r7eis evidence of growth Fail the test for sterility 24
31. leakage testing
Mr. Kailash Vilegave 31
T h e sealed ampoules are subjected to small cracks which occurdue
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.
32. Clarity Test:
Mr. Kailash Vilegave 32
Performed to ensure that the parenteral productsare
free from foreign particles.
Method: Visual Method,
Coulter Counter Method
Filtration Method
Particle Size (μm) equal to
or large than
Max. no. o f particlesper
ml
10 50
25 5
50 nill
33. Pyrogen Testing
Mr. Kailash Vilegave 33
Pyrogen = “Pyro” (Greek = Fire) + “gen” (Greek = beginning).
Fever producing, metabolic by-products of microbial growth and
death.
Bacterial pyrogens are called “Endotoxins”. Gram negative
bacteria produce more potent endotoxins than gram + bacteria
and fungi.
Endotoxins are heat stable lipopolysaccharides (LPS) present in
bacterial cell walls.
Stable to at least 175oC; steam sterilization ineffective
Water soluble; monomer unit of LPS can be 10,000 Daltons (1.8
nm) so endotoxins can easily pass through 0.22μm filters
Sources: Water (main), raw materials, equipment, process
environment, people, and protein if using gram negative ba cteria.
34. Biological properties of endotoxin
:
Mr. Kailash Vilegave 34
Pyrogen elevate the circulatory levels of inflammatory
cytokines which may be followed by fever, blood coagulation,
hypotension
Low doses of Pyrogen: asymptomatic inflammationreaction
Moderate doses: fever & changes in plasma composition
High doses:
vasoconstriction,
cardiovascular dysfunction,vasodilation,
endothelium dysfunction, multiple organ
failure & finally death.
35. Elimination of pyrogens
Mr. Kailash Vilegave 35
Dry heat sterilization : For glass wares, metal equipments,
powders, waxes, oils, heat stable drugs
650 o C temp - 1 min
250 o C temp - 30 min
180 o C temp - 240 min
Ultra filtration
Reverse osmosis : RO membrane is composed of cellulose
acetate phthalate/ polyamide
Distillation
Adsorption method
36. Rabbit PyrogenTest:
Mr. Kailash Vilegave 36
Rabbits are used to perform this test because their body temp
increases when pyrogen are introduced into their bodies by
parenteral route
3 healthy adult rabbits of either sex, each weighing NLT 1.5 kg are
selected
Do not use anyrabbit
having a temp higher than 39.8 oC
o CShowing temp variation >0.2 between two successive
reading in the determination of initial temp
Sham test is performed within 7 days of actual test
oAnimal showing temp increase over 0.6 C should beremoved
from pyrogen testing
37. • Method :
Dissolve the subs being examined in, or dilute it with a pyrogen
free saline solution
Warm the liquid being examined to approx. 38.5o C temp before
injection
The volume of injection is NLT 0.5ml/kg & NMT 10ml/kg of body
weight
Withhold water during test
Clinical thermometer is inserted into the rectum of rabbit to
record body temp
2 normal reading of rectal temp are should be taken prior to the
test injection at an interval of half an hr & its mean is calculated-
initial temp
The solution under test is injected through an earvein
Record the temp of each rabbit in an interval of 30 min for 3 hrs
The difference between initial temp & maximum temp is
recorded- taken as response
Mr. Kailash Vilegave 37
39. Bacterial endotoxin (LAL) test )
Mr. Kailash Vilegave 39
To detect or quantify endotoxins of gram-ve bacterial origin
Reagent: amoebocyte lysate enzyme from horseshoe crab
(Limulus polyphemus or Tachypleus tridentatus).
The name of the test is also Limulus amebocyte lysate (LAL)
• Mteecshtanism of LAL Test:
The test is based on the gelling properties of enzyme extracted
from the horseshoe crab of Limulus polyphemus.
enzymes when come in contact with bacterial endotoxin
Gelling
Degree of Gelling related to amount of Endotoxin present
05/02/17
H.P.I Rishi Ram Parajuli
33
40. • Test performance (short)
Avoid endotoxin contamination
– Before the test:
– interfering factors should not be present
– equipment should be depyrogenated the sensitivity of the
lysate should be known
Test:
– equal Volume of LAL reagent and test solution (usually 0.1 ml
of each) are mixed in a depyrogenated test-tube
– Incubation at 37°C, 1 hour
– remove the tube - invert at (180°) observe the result
H.P.I Rishi Ram Parajuli0–5/0p2/1a7ss-failtest 34Mr. Kailash Vilegave 40
41. LAL test
Mr. Kailash Vilegave 41
Three differenttechniques:
1. The gel-clot technique - gel formation
2. The turbidimetric technique - the development of Turbidity
after cleavage of an endogenous substrate
3. The chromogenic technique - the development of color after
cleavage of a synthetic peptide- chromogen complex
• Advantages of LAL test
Fast - 60 minutes vs. 180 minutes
Greater Sensitivity ,Less Variability
Much Less False, Positives ,Much Less Expensive
Alternative to Animal Model, cheaper,
particularly useful for:
Radiopharmaceuticals and cytotoxic agents
Blood products
Water for injection
35
42. MAT (Monocyte Activation
Test)
Mr. Kailash Vilegave 42
D u e to its greater sensitivity replaces LAL Test.
Uses monocyte obtained from Human volunteeror
blood bank
Detects pro-inflamatory and pyrogenic
contaminants.
Used or Qualitative and Quantitativedetection.
43. Production facilities of parenterals
Mr. Kailash Vilegave 43
preparation are The production area where the parenteral
manufactured can be divided into five sections:
Clean-uparea
Preparation area
Aseptic area
Quarantine area
Finishing & packaging area
44. Clean-up area:
44
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.
45. Aseptic area:
Mr. Kailash Vilegave 45
The parenteral preparations are filtered, filled into final
container & sealed 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.
46. Quarantine area:
Parenteral products are properly labelled and packed.
Properly packing is essential to provide protection
against physical damage.
The labelled container should be packed incardboard or
plastic container.
Ampoules should be packed in partitioned boxes
Mr. Kailash Vilegave 46
After filling, sealing & sterilization the parenteral product are
held up in quarantine area.
Randomly samples were kept for evaluation.
The batch or product pass the evaluation tests are transfer in
to finishing or packaging area.
Finishing & packaging area:
47. Lyophilization or freeze drying
Mr. Kailash Vilegave 47
Lyophilization or freeze drying is a process in which water is
removed from a product after it is frozen and placed under a
vacuum, allowing the ice to change directly from solid to vapor
without passing through a liquid phase.
T h e process consists of three separate, unique, and interdependent
processes;
Freezing,
Primary drying (sublimation),and
Secondary drying (desorption).
48. T h e advantages of Lyophilizationinclude:
Ease of processing a liquid, which simplifies aseptichandling
Enhanced stability of a drypowder
Removal of water without excessive heating of theproduct
Enhanced product stability in a drystate
Rapid and easy dissolution of reconstitutedproduct
Disadvantages of Lyophilization include:
Increased handling and processing time
Need for sterile diluent uponreconstitution
Cost and complexity ofequipment
Mr. Kailash Vilegave 48
49. Mr. Kailash Vilegave 49
Containers for parenteral
1.Glass
2. Plastic
3.Rubber closers
50. SELECTION CRITERIA FOR PACKAGING MATERIAL
• The product or pack contents
• The application of the product
• Content stability, and the need of protection form any
environmental factors
• Content reactivity (with relevant to the packaging material)
• Acceptability of the pack to the consumer or user
• The packaging process
• Regulatory, legal and quality issues
51. Characteristics of packaging material
• They must protect the preparation from environmental
conditions.
• They must not be reactive with the product.
• They must not impart to the product tastes or odors.
• They must be nontoxic.
• They must be FDA approved.
• They must meet applicable tamper-resistance
requirements.
• They must be adaptable to commonly employed high
speed packaging equipment.
52. List of packages for sterile dosage forms
• All types of parental
ampoules
vials
i.v. infusion (small vol. + large vol.)
s.c injections
intra thecal inj.
intramuscular inj.
• Oral vaccines
tripsules
• Ophthalmic product
drops
ointment
53. Using of packaging material
vaccine storage,I)Glass - ampule, vials, syringe, SVI, LVI,
dropper (primary packaging)
II) Metals - vials (primary packaging)
III)Rubbers – vials, syringe’s plunger, vaccine closer (primary
packaging)
IV)Plastics - ampule, vials, syringe, SVI, LVI, vaccine storage,
dropper, tripsules, (primary packaging as well as secondary
packaging)
V)Fibrous mater- all types of secondary packaging
VI)Films, Foils and laminates –all types of secondary packaging
54. GLASS:
• Glass has been widely used as a drug packaging material.
• Glass is composed of sand, soda ash, limestone,& cullet.
• Si, Al, Na, K, Ca, Mg, Zn & Ba are generally used into preparation of glass
Advantages
• They are hygienic and suitable for sterilization
• They are relatively non reactive ( depending on the grade chosen)
• It can accept a variety of closures
• They can be used on high speed packaging lines
• They are transparent.
• They have good protection power.
• They can be easily labeled.
DISADVANTAGES
• It is relatively heavy
• Glass is fragile so easily broken.
• Release alkali to aqueous preparation
55. TYPES OF GLASS:
Type I ( Neutral or Borosilicate Glass)
Type II ( Treated Soda lime glass)
Type III ( Soda lime glass)
Type IV ( General purpose soda lime glass)
TYPE I GLASS
• Least reactive.
more sensitive• Higher ingredients and processing cost therefore used for
pharmaceutical products such as parenteral or blood products.
• Mostly ampoules and vials are made up of Type I glass.
56. Type II glass:
pe I. Higher chemical resistance but not as much as ty
Cheaper than Type I.
Acceptable for most products accept blood products and
aqueous pharmaceutical with a pH less than 7
Type III glass
Have similar composition and are distinguished from each
other on the basis of their hydraulic resistance
it has average or slight better than average resistance and is
suitable for non- aqueous parenterals and non parenteral
products.
Type III glass containers are normally dry
sterilized before being filled.
57. Type IV glass:
lowest hydraulic resistance and is suitable for solid
products, some liquids and semi solids and not for
parenteral.
59. 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.
60. Plastic
Thermoplastic polymers have been established as
packaging materials for sterile preparations such
60
as large-volume parenteral's,
solutions and increasingly,
ophthalmic
small-volume
parenteral's.
Three principal problem areas exist in using these
materials:
1. Permeation of vapours and other molecules in either
direction through the wall of the plastic container.
2. Leaching of constituents from the container to the product.
3. Sorption(absorption and/or adsorption) of drug
molecules or ions on the plastic materials.
61. Plastic polymers used for parenteral
packages include polyvinylchloride (PVC) and
polyolefin.
PVC is flexible and nonrigid.
Polyolefin is semirigid; unlike PVC, it can be
stored upright.
Both types of plastic offer several advantages
over glass, including durability, easier
storage and disposal, reduced weight, and
improved safety.
61
62. Mr. Kailash Vilegave 62
Plastic containers are used but they face following problems
• Permeation
• Sorption
• Leaching
• Softening
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
Closure:
63. • 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
65. WATER ATTACK TEST
• This test is used only with containers that have been
exposed to sulphur dioxide fumes under controlled humidity
conditions. Such a treatment neutralizes the surface alkali.
Now the glass becomes chemically more resistant. The
principle involved in the water attack test is to determine
whether the alkali leached form the surface of a container is
within the specified limits or not. Since the inner surface is
under test entire container (ampoule) has to be used. The
amount of acid that is necessary to neutralize the released
alkali from the surface is estimated, the leaching of alkali is
accelerated using elevated temperature for a specified time.
Methyl red indicator is used to determine the end point. The
basic is acid-base titration.
66. TESTS CONTAINER VOL.OF 0.02N H2SO4
Powdered glass test Type I
Type II
Type III
1.0
8.5
15.0
Water attack test
Type II(100ml or below)
Type II(above 100ml)
0.07
0.02
67. QUALITY CONTROL TESTS FOR GLASS CONTAINERS:
CHEMICAL RESISTANT OF GLASS CONTAINERS
A) POWDERED GLASS TEST :
It is done to estimate the amount of alkali leached from the powdered glass
which usually happens at the elevated temperatures. When the glass is
powdered, leaching of alkali is enhanced, which can be titrated with 0.02N
sulphuric acid using methyl red as an indicator .
o Step -1 : Preparation of glass specimen : Few containers
are rinsed thoroughly with purified water and dried with stream of clean
air. Grind the containers in a mortar to a fine powder and pass through
sieve no.20 and 50.
o Step -2 : Washing the specimen : 10gm of the above
specimen is taken into 250 ml conical flask and wash it with 30 ml
acetone. Repeat the washing, decant the acetone and dried after which it is
used within 48hr.
Procedure :
10gm sample is added with 50ml of high purity water in a 250ml flask. Place
it in an autoclave at 121⁰C±2⁰C for 30min.Cool it under running water.
Decant the solution into another flask, wash again with 15ml high purity
water and again decant. Titrate immediately with 0.02N sulphuric acid
using methyl red as an indicator and record the volume.
68. 2) HYDROLYTIC RESISTANCE OF GLASS
CONTAINERS:
• Rinse each container at least 3times with CO2 free water
and fill with the same to their filling volume. Also fill &
Cover the vials and bottles and keep in autoclave. Heat to
100⁰C for 10min and allow the steam to issue from the vent
cork. Rise the temp from 100⁰C to 121⁰C over 20min.
Maintain the temp at 121⁰C to 122⁰C for 60min.Lower the
temp from 121⁰C to 100C over 40min venting to prevent
vacuum.
• Remove the container from autoclave, cool and combine
the liquids being examined. Measure the volume of test
solution into a conical flask and titrate with 0.01M HCl
using methyl red as an indicator. Perform blank with
water and the difference between the titration represents
the volume of HCl consumed by the test solution.
69. 3) ARSENIC TEST:
• This test is for glass containers intended for aqueous
parenterals. Wash the inner and outer surface of container
with fresh distilled water for 5min.Prep test as described in
the test for hydrolytic resistance for an adequate no.of
samples to produce 50ml.pipette out 10ml solution from
combined contents of all ampoules to the flask.
• Add 10ml of HNO3 to dryness on the water bath, dry the
residue in an oven at 130⁰C for 30min cool and add 10ml
hydrogen molybdate reagent .Swirl to dissolve and heat under
water bath and reflux for 25min. Cool to room temp and
determine the absorbance at 840nm.
• Do the blank with 10ml hydrogen molybdate. The absorbance
of the test solution should not exceed the absorbance obtained
by repeating the determination using 0.1ml of arsenic
standard solution (10ppm) in place of test soln.
70. 4 ) THERMAL SHOCK TEST:
• Place the samples in upright position in a tray.
Immerse the tray into a hot water for a given
time and transfers to cold water bath, temp of
both are closely controlled. Examine cracks or
breaks before and after the test. The amount of
thermal shock a bottle can withstand depends on
its size, design and glass distribution. Small
bottles withstand a temp differential of 60 to
80⁰C and 1 pint bottle 30 to 40⁰C.A typical test
uses 45C temp difference between hot and cold
water.
71. The test bottle is filled with water and
placed inside the test chamber
A scaling head is applied and the
internal pressure automatically raised
by a series of increments each of which
is held for a set of time
The bottle can be checked for
predetermined pressure level and the
test continues unteil the container finally
bursts.
INTERNAL BURSTING PRESSURE TEST
• The most common instrument used is American glass
research increment pressure tester .
72. 6 ) LEAKAGE TEST:
• Drug filled container is placed in a container
filled with coloured solution (due to the addition
of dye)which is at high pressure compared to the
pressure inside the glass container so that the
coloured solution enters the container if any
cracks or any breakage is present.
73. Place a 4ml of water in each of 12 clean vials. Close a vial with
closure and secure caps for 16 hrs.
Pierce the closure with 21 SWG hypodermic needle. Repeat the
operation 4 times for each closures.
Count the number of fragment visible on the rubber . Total
number of fragment should not be more than 10 except butyl
rubber
QUALITY CONTROL TESTS FOR RUBBERS :
• Fragmentation test for rubber closures :
74. QUALITY CONTROL OF CLOSURES
• PREPARATION OF SAMPLE (SOL.-A) :
Wash closures
in 0.2%w/v of
anionic
surface active
agents for
5min.
Rinse 5 times with dist
water and add 200ml water
and is subjected to
autoclave at 119 to 123⁰C
for 20 to 30min covering
with aluminum foil.
Cool and
separate
solution from
closure (soln-A)
75. 1) STERILITY TEST:
• When treated closures are subjected to
sterilization test at 64-66⁰C and a pressure of
about 0.7 KPa for 24hr.
76. 2) Fragmentation test
For closures for aqueous place a vol of water corresponding to the
nominal vol minus 4 ml in each of 12 clean vials.
close the vials with the ‘prepared’ closures & allow to stand for 16
hours.
For closures for dry preparations close 12 clean vials with the
‘prepared’ closures.
Using a hypodermic needle with an external diameter of 0.8 mm
inject 1 ml of water into the vial and remove 1 ml of air.
Carry out this operation 4 times with new needle each time Pass the
liquid in the vials through a filter with a pores size of 0.5 µm.
No. of fragments is NMT 10 except in the case of butyl rubber
closures where the total no. of fragments is NMT 15
77. 3)Self – sealability test:
• This test is applicable to closures intended to be used
with water close the vials with the ‘Prepared’ closures
• For each closure, use a new hypodermic needle with an
external diameter of 0.8 mm & pierce the closure 10
times, each time at a different site.
• Immerse the vials upright in a 0.1% w/v solution of
methylene blue & reduce the external pressure by 27KPa
for 10 min.
• Restore the atmospheric pressure and leave the vials
immersed for 30 minutes. Rinse the outside of the vials.
None of the vials contains any trace of coloured solution.
78. 4 ) PH OF AQUEOUS EXTRACT:
• 20ml of solution A is added with 0.1ml
bromothymol blue when it is added with a small
amount of 0.01M NaOH which changes the
colour from blue to yellow. The volume of NaOH
required is NMT 0.3ml and if it is done with
HCl, the volume of HCl needed should NMT
0.8ml.
79. 5 ) LIGHTABSORPTION TEST:
• It must be done within 4hrs of preparing
solution A. It is filtered through 0.5μ filter and
its absorbance is measured at 220 to
360nm.Blank is done without closures and
absorbance is NMT 2.0.
80. 6 ) REDUCING SUBSTANCES:
20ml of solution A is added with 1ml of 1M
H2SO4 and 20ml of 0.002M KMnO4 and boil
for 3min then cool and add 1gm of potassium
iodide which is titrated with sodium thio-
sulphate using starch as an indicator. Blank is
done and the difference between titration
volumes is NMT 0.7ml.
81. 7 ) RESIDUE ON EVAPORATION:
• 50ml of solution A is evaporated to dryness at
105⁰C.Then weigh the residue NMT 4mg.
82. TEST FOR PLASTIC CONTAINERS:
• 1.For non-injectable preparations:
Leakage test / Collapsibility test : Applicable to
containers which are to be squeezed in order to
remove contents. yield 90%of its contents at
required rate of flow at ambient temp. Fill 10
containers with water Fit with closures Keep them
inverted at room temp. 24hrs No signs of leakage
83. CLARITY OF AQUEOUS EXTRACT:
• Clarity of aqueous extract Select unlabelled portion
from a suitable containers Cut these portions into
strips Wash it with extraneous matter by shaking with
two separate portions of distilled water Transfer to
flask – previously washed with chromic acid Rinse
with distilled water add 250ml d.w. Cover the flask
autoclave at 121Ċ, 30min Colourless , free from
turbidity
84. NON VOLATILE RESIDUE TEST:
• Non volatile residue test 2. Injectable
preparations: a. Leakage test b. Collapsibility
test C. Transperancy: Fill 5 containers with dil.
Suspension. The cloudiness of of the diluted
suspension in each container is detectable when
viewed through the containers as compared with
a container of the same type filled with water
Evaporate 100ml extract Allow it to dry at 105Ċ
Residue weighs not more than 12.5mg
85. WATER VAPOUR PERMEABILITY:
• Fill 5 containers with nominal volume of water
and heat seal the bottles with aluminium foil.
Weigh accurately each container and allow to
stand for 14 days humidity- 60±5% temp. 20Ċ
and 25Ċ. Reweigh the containers. Loss in wt in
each container is NMT 0.2% Specifications and
tests of plastic container materials: Barium
Heavy metals Tin zinc 19
86. Quality test is designed to achieve-
1. Consistency
2. Purity
3. Stability
And to avoid-
1. Damage
2. Contaimination
3. degradation
87. Laboratory Analysis
• Visual inspection
• Identification test
• Dimentional test
• Physical test
• Chemical test
• Microbiologcal test
• Permormance measurements