lvp, svp, formulation of parenterals,water for injection,etc

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2. SUBMITTED BY
JISNA SEBASTIAN
FIRST YEAR MPHARM 2

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The term derived from Greek word ‛Para’ outside &
‛Enterone’ 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.
Term parenteral used for any drug/fluid whose delivery
doesn’t utilize the alimentary canal for entering in to the
body tissues.

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• Stability
• Sterility
• Free from pyrogens & toxins
• Free from foreign particles
• Isotonic
• Chemical purity

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PARENTERAL ROUTES
The term parenteral literally means to avoid the
gut (gastrointestinal tract) and refers to any route of
administration outside of or beside the alimentary tract.
Thus, parenterals are injectable drugs that enter the body
directly and are not required to be absorbed in the
gastrointestinal tract before they show their effect.
Parenteral routes of administration usually have a more rapid
onset of action than other routes of administration.

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1. Intravenous
2. Intramuscular
3. Subcutaneous
4. intradermal
5. Intra-arterial
6. Intracardiac
7. Intrathecal
8. Intracisternal
9. Peridural
10.Intraarticular
11.Intracerebral
PARENTERAL ROUTES

7. Intravenous
• The injection of a drug
directly into the patient's
veins, resulting in the
most rapid onset of action.
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Intradermal
The drug is injected into the top
few layers of the skin. Ideally,
the drug is placed within the
dermis. Used for diagnostic
agents.
Subcutaneous
The injection of the drug under
the skin into the fatty layer,
but not into the muscle.
Absorption of the drug is rapid.
Eg; insulin

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Intramuscular
Drugs are injected deeply into
muscle tissue. If the drug is in
aqueous (water) solution,
absorption is rapid. However, if
the drug is in an oily liquid or in
the form of a suspension, it can
prolong the release of the drug.

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Useful for patients who cannot take drugs orally
Rapid onset of action
Useful for emergency situations
Providing sustained drug delivery (implants, im depot inj)
Avoid first pass metabolism
Can inject drug directly in to a tissue (target drug delivery)
Useful for delivering fluids, electrolytes, or nutrients (TPN)
Can be done in hospitals, ambulatory infusion centers and
home health care centers
Complete bioavailability.

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Pain on injection
Difficult to reverse an administered drug’s effect.
Sensitivity or allergic reaction at the site of injection.
Requires strict control of sterility & non pyrogenicity than
other formulation.
Trained person is required.
Require specialized equipment, devices, and techniques
to prepare and administer drugs.
More expensive and costly to produce.

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1. Small volume parenterals (SVP)
2. Large volume parenterals (LVP)

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USP defn: An injection that is packed in containers labeled as
containing 100 ml or less.
Defn: LVP are parenterals designed to provide :-
Fluid
Calories (dextrose solution )
Electrolytes
Combenation of these
Volume 101- 1000 ml

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parameter SVP LVP
volume 100 ml or less 101-1000 ml
Routes IV, IM & SC IV- LVP & non IV- LVP
Dosage unit Single or multiple Single
preservative Used Not used
Buffers Used Not used
Formulation Soln, emulsion,suspension. Soln & o/w nutrient
emulsion
Isotonicity Not essential must
Pyrogenicity Not essential must
use Therapeutic & diagnostic Nutrition,detoxification,
And during surgery

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AQUEOUS VEHICLE :
WATER FOR INJECTION (WFI) USP :
Highly purified water used as a vehicle for injective
preparations which will be subsequently sterilized.
USP requirement include not more than 10 parts per million
of total solids.
pH of 5.0 – 7.0 .
WFI may be prepared by either distillation or reverse osmosis.
 Stored in chemically resistant tank.

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BACTERIOSTATIC WATER FOR INJECTION
This type of water used for making parenteral
solutions prepared under aseptic conditions and not
terminally sterilized.
Need to meet USP sterility test.
It can contain an added bacteriostatic agent when
in containers of 30 ml or less.

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STERILE WATER FOR INJECTION
SWFI containing one or more suitable bacteriostatic agent.
 multiple – dose containers not exceeding 30 ml.
They are permitted to contain higher levels of solid than
WFI because of possible leaching.
Used for washing wounds , surgical incisions, or body
tissues.

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WATER MISCIBLE VEHICLES
The number of solvents that are miscible with water has
been used as a portion of a vehicle.
Primarily to affect solubility of drugs and to reduce
hydrolysis.
Example:
Ethyl alcohol,
Liquid propelene glycol
Glycerine
Ethyl alcohol used in the case of cardiac glycoside.

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NON – AQUEOUS VEHICLES
Fixed oils (vegitable origin, liquid, and rancid resistance
,unsaturated, free fatty acid content )
Peanut oil
Corn oil
Cotton seed oil (depo-testosterone)
Sesame oil
Soyabean oil
Ethyl oleate
Isopropyl myristate.

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ANTIBACTERIAL AGENTS
These are added in multiple dose containers.
To prevent microorganism growth
Limitted concenteration of agents are used.
Phenyl mercuric nitrate and thiomersol 0.01%.
Benzethonium chloride & benzalkonium chloride 0.01%.
Phenol & cresol 0.05%.
Chlorobutanol 0.05%.

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BUFFERS
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.

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ANTIOXIDENT
To protect the formulation from oxidation
Two types
1. Reducing agents
Ascorbic acid
Sodium bisulfite 0.01%
Thiourea
2.Blocking agents
Tocopherol

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SURFACTANTS
 Solubilise the active ingredient
Polyoxythylene sorbitan monooleate & Sorbitan
monooleate 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 Effect of different solutions on blood cells

26. CHELATING AGENTS
 To remove trace elements that catalyse oxidative
degeneration
Ethelene diamine tetra acetic acid
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CO-SOLVENT
 Improve solubility
 Prevent potential for hydrolysis

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BULKING AGENTS
 For freeze dried preparations(solids)
Mannitol
Lactose ,sucrose
Dextran .
SUSPENDING AGENTS
CMC,
Methyl cellulose, Gelatin
Sorbitol .
EMULSIFYING AGENTS
Lecithin
Polysorbate 80

28.  A clear and colorless liquid; odorless.
 Water for injections is pyrogen -free.
 It contains no added substance.
 Water for injections is obtained from potable or Purified
water by distillation in an apparatus.
 The distillate is collected and stored in conditions
designed to prevent growth of microorganisms and to
avoid any other contamination.
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29. • The source water usually must be pretreated by one
or a combination of following treatment:
• Chemical softening, filtration, deionization, carbon
absorption, or reverse osmosis purification.
• There are three types of distillation still to produce
water for injection.
1. Compression distillation
2. Multiple-effect still
3. Reverse osmosis
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30. • Vapor compression still is primarily designed for the
production of large volumes of high purity distillate with low
consumption of energy and water.
• Vapor compression processes produce water 5 to 10 times
more cost effectively than multiple effect distillers.
• PROCEDURE:
• Step 1: In a Vapor Compression still, the boiling process
begins with both heating elements turned on. As the water in
the boiling chamber reaches near boiling temperatures, the
compressor turns on.
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31. • Step 2: In the compressor, the steam is pressurized, which
raises the steam's temperature before it is routed through a
special heat exchanger located inside the boiling chamber.
• Step 3: The pressurized steam gives off its heat to the tap
water inside the boiling chamber, causing this water to boil,
which creates more steam.
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32. • Step 4: While the pressurized steam is giving up its
latent heat, the steam will condense. One of the
heating elements will cycle on and off periodically as
needed.
• Step 5: At this stage, the condensed steam is
considered distilled water but is still very hot--only
slightly cooler than boiling temperature.
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COMPRESSION STILL

34. • It is also designed to conserve energy and water usage.
• In principle, a series of single effect stills running at different
pressures.
• A series up to seven effect may be used, with the first effect
operated at a highest pressure and the last effect at
atmospheric pressure.
• The capacity of still can be increased by adding effects. The
quantity of distillate will also be affected by inlet steam
pressure 34

35. PRODEDURE:
 Steam from the external source is used in the first effect
to generate steam under pressure from feed water, it is
used as a power source for second effect.
 The steam used to drive the second effect condenses
as it gives up its heat of vaporization and forms a
distillate.
 The process continues until the last effect, when the
steam is at atmospheric pressure and must be
condensed in a heat exchanger. 35

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37. REVERSE OSMOSIS:
• The natural process of selective permeation of molecule
through a semi-permeable membrane separate two aqueous
solutions of different concentration is reversed.
• Pressure, usually between 200 to 400 psig, is applied to
overcome osmotic pressure and force pure water to
penetrate through the membrane.
• Membrane composed of cellulose esters or polyamides.
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•. It provide effective rejection of contaminant molecules in
raw water.
•Sodium chloride is most difficult to remove.
•Passage through two membranes in series is sometimes
used to increase the efficiency of removal of small
molecules.
• ex. Aqua chem , Finn-aqua, Meco , Milipore etc.

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40. STORAGE AND DISTRIBUTION
• Distillate is collected in holding tanks for subsequent use.
• USP permit the storage of WFI at room temp. maximum for
only about 24hr.
• When the water can not be used at 80º c , heat exchangers
must be installed to reduce the temperature at the point of
use.
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LARGE VOLUME PARENTERALS
REQUIREMENTS
Sterile, non pyrogenic, free from particulate matter
Volume 101- 1000ml
Single dose unit
No preservative
Clear solution except fat emulsion
Isotonic, but hypertonic also administered in TPN

42. TYPES OF LARGE VOLUME PARENTERALS
1.HYPER
ALIMENTATION
SOLUTIONS
2. CARDIOLPAGIC
SOLUTIONS
3. PERITONIAL
DIALYSIS SOLUTION 4. IRRIGATING SOLUTIONS
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HYPERALIMENTATION SOLUTION
Admin. Of large amount of nutrients to patients who unable
to take food orally.
Formulation: mix. Of dextrose, amino acids , lipids,
electrolytes,& vitamines.

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TOTAL PARENTERAL NUTRITION
Def. :A method of feeding patients by infusing a mixture
of all necessary nutrients into the circulatory system, thus
bypassing the GIT.
CONTENT SOURCES
1. calories Dextrose
2. Nitrogen Crystalline amino acids
3. Electrlyte Na , K, Cl , Po4,
4. Vitamines Water soluble & Fat soluble
5. Elements Traces of Zn, Cu, Mn, Cr

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2. CARDIOLPLEGIC SOLUTIONS
Are LVP used in heart surgery to prevent injury to
myocardium during reperfusion, as well as to maintain
bloodless operating field.
Maintains the diastolic arrest.
Administerd in cold form.
Slightly alkaline to compensate metabolic acidosis,
Hypertonic
USE:
To minimize reperfusion injury resulting from tissue
edema.

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3. PERITONEAL DIALYSIS SOLUTION
 Infused continuously into abdominal cavity, bathing
peritonium & are then continously withdrawn.
USE
Removal of toxic substances from body.
To aid & accelerate excretion normal.
To treat acute renal insufficiency.

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4. 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 soln
should not be used parenterally.
Use: Treatment of serious wounds infused in to blood
stream.

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EXAMPLES OF LVP

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Small volume parenterals
• Small volume intravenous injection is applied to an injection that is
packaged in containers labelled as containing 100 ml or less.
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1. Solution:
2. Suspension:
3. Emulsion:
4. Dry powders:

50. solutions
• Typically used for delivering medications at a controlled infusion rate
• Most commonly solutions of 5% dextrose, normal saline, 45% normal
saline, or 5% dextrose with normal saline.
• Dextrose contributes glucose to meet energy needs and saline
contributes sodium, an electrolyte that maintains fluid balance and
cellular functions.

51. SUSPENSION
• They should be sterile, pyrogen free, stable,
re‐suspendable, syringeable, injectable, isotonic &
non‐irritating.
• They are usually administered by either subcutaneous
(S.C.) or intramuscular (I.M.) route.
• These suspensions usually contain between 0.5% and
5.0% solids & should have particle size less than 5
micrometer for I.M. or S.C. administration.
• Certain antibiotic preparations (For example procaine
Penicillin G) may contain up to 30% solids
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52. • Advantages of Parental suspension
• It is better for the therapeutic use of drugs that are
insoluble in convention solvents.
• In this dosage from there is increased resistance to
hydrolysis & oxidation as drug is present in the solid
from.
• Formulation of controlled released drug is possible in
this dosage form.
• There is elimination of hepatic first pass effect.
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53. Injectable Emulsion-
• An emulsion is a heterogenous dispersion of one
immiscible liquid in another.
• This inherently unstable system is made possible
through the use of an emulsifying agent, which prevent
coalescence of the dispersed droplet.
• Parenteral emulsion are rare because it is necessary
(and difficult) to achieve stable droplet of less than 1
micron meter to prevent emboli in blood vessels and it is
not usually necessary to achieve an emulsion for drug
administration. 53

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Dry Powders
Purpose: To overcome the intrinsic instability of the drug, be
reconstitute before use.
• Production Method:
– Freeze-drying
–Aseptic crystallization and dry powder filling
– Spray-drying

55. • Pharmaceutical product development by
N K Jain.
• Theory and practice of industrial pharmacy by
Lachman and Leiberman.
• www. Google.com.
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REFERENCE

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