2. PARENTERAL PRODUCTS
.
Parenteral products are intended for use by injection under or through one or
more layers of the skin or mucous membranes.
• They must be free from microbial contamination and from toxic
components as well as possess an exceptionally high level of purity.
• All components and all processes involved in the preparation of these
products must be selected and designed to eliminate contamination of all
types, whether of physical,chemical or microbiological origin.
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3. PRODUCT
DEVELOPMENT
• The final sterile product must give a therapeutic effect
in a patient.
• The effect of physical and chemical factors on
preparation be minimum.
• The preferred preparation for neural use are solution
preparation for intramuscular, subcutaneous,
intradermal use can be solutions,suspensions or
emulsions.
• The chemical and physical properties of a drug must be
analyzed for knowledge about onset of
action,interaction with excipients and stability.
• The solvent system should produce no tissue irritation
thus be free from any traces.
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6. • Fast- acting route because the drug goes directly into the bloodstream.
• Often used in the emergency department and in critical care areas.
• Commonly used
- for fluid and electrolyte replacement
- to provide necessary nutrition to the patient who is critically ill
• Intravenous injections are administered at a 15 to 20
degree angle.
• Volume NMT 1 litre.
• Example - Dextrose, Mannitol
INTRAVENOUS INJECTIONS
.
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7. INTRAMUSCULAR INJECTIONS
• In adults, IM injections are given into upper, outer portion of the gluteus
maximus.
• For children and some adults IM injections are given into the deltoid
muscles of the shoulders.
• Typical needle is 22-25 gauge 1/2 to 1 inch needle.
• IM injections are administered at a 90 degree angle.
- volume limited to less than 2 ml
• Example- Cephalosporin, Morphine, Haloperidol
.
.
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8. SUBCUTANEOUS
• Administer medications below the skin into the subcutaneous
fat.
• Often have a longer onset of action and a longer duration of
action compared with IM or IV injection.
• Given at a 45-degree angle
- 25-or 26 gauge needle , 3/8 to 5/8 inch length
• Not more than 1 ml should be injected into the site to avoid
pressure on sensory nerves causing pain and discomfort.
• Example - Insulin, Morphine
9. .
INTRA-ARTERIAL INJECTION
• Drug administered within or into the artery or arteries.
• Example- Anticancer agent for drug targeting to a
particular organ.
INTRACARDIAC INJECTION
• These are given directly into the heart muscle or ventricles at the
time of emergency only.
• Example- Antiarrthymatic drugs, Quinidine,Propanolol.
10. .
INTRATHECAL INJECTION
• These are given into the subachonoid space
that surround the spinal cord.This route is used for
spinal anesthesia.
PERIDUAL INJECTION
• These are given between the dura matter and inner
aspect of vertebra.
• Used for given spinal anesthesia.
11. .
INTRA-ARTICULAR INJECTION
• These are given into the articulating ends
of bones in the joints.
• Injections of antibiotics and corticosteriods are
administered in inflammed jointed cavities by experts.
INTRACEREBRAL INJECTION
• Drugs are introduced or administered into the cerebrum.
• Example- Adrenaline, Amphetamine
12. .
INTRAOCULAR
• Drugs are administered by entering the eyeball and around
the eyes.
• Example- Avastin, Carbacol
INTRA-ABDOMINAL
• Drugs are admininstered through the cavity of the abdomen.
And this is one given to intraperitoneal.
• Example- Dialysis soltion. Heparin
13. COMPONENTS OF PARENTERAL
PREPARATION
VEHICLE
1. Aqueous Vehicle -
• water for injection
• bacteriostatic water for injection
• water miscible vehicles
• tested for solid content, pyrogens and ions
2. Non- Aqueous Vehicle-
• used in combination with water: dioxolanes, dimethyl acetamide N- (2-
hydroxyethyl) - lactamide, butylene glycol, glycerin and ethyl alcohol.
• water immmicible solvents: fixed oils (peanut oil, cotton seed oil)ethyl
oleate, isopropyl myristate, benzyl benzoate.
14. ADDED SUBSTANCES
ANTIBACTERIAL AGENTS : added to multiple doses injection to prevent
microbial growth. For eg-phenol and cresol (0.05%)
BUFFERS : it maintains the pH of the solution and prevents chemical degradation.
For eg- Acetate and citrate buffer
ANTI-OXIDANTS : to protect the formulation for oxidation.
Two types of anti oxidants.
• Reducing Agents : eg - ascorbic acid, thiourea
• Blocking Agents : eg- tocopherol
SURFACTANTS : added to solubilise the active ingredient.For eg- sorbitol,
monooleate
TONOCITY AGENTS : it is needed to maintain the formulation to be isotonic
with the body fluids to avoid the destruction of ed blood cells, irritation and tissue
damage. For eg- NaCl, KCl, Dextrose
CHELATING AGENTS : to trace elements that catalyse oxidative degeneration.
For eg- EDTA
15. CLASSIFICATION OF PREPARATION
Small Volume Parenteral Large Volume Parenteral
• An injection that is packed in containers
labelled as containing 100 ml or less
• An injection that is packed in containers
labelled as containing 101ml - 1000ml
• Single or multiple use • Single use
• Preservatives are used. • Preservatives are not used
• Administered through various parenteral
routes.
• Administered through IV infusion
technique
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17. TYPES OF LARGE VOLUME PARENTERALS
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Hyper alimentation solution
• Administration of nutrients to the patient
who is unable to take them orally.
• Eg mixture of dextrose, amino acids,
lipids, vitamins etc.
Cardioplegic solution
• Used in heart surgery to prevent injury in
myocardium.
Peritoneal Dialysis
• Infused into abdominal cavity
• Remove toxic substances from the body
Irrigation solution
• To irrigate flush and aid body cavities and
wounds.
• Eg- saline solution
18. TYPES OF PARENTERAL PREPARATIONS
BASED ON MODE OF DELIVERY
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INJECTIONS- Injections are sterile,pyrogen freesolutions or dispersions (emulsions or
susensions) of one or more active ingredients in a suitable vehicle.
• Single- dose injections : They should not contain antimicrobials preservatives unless
justified and authorized. Injections with antimicrobial preservative must not be
administered intracisternally, intrathecally, epidurally or by any route giing access to
the cerebrospinal fluid, or intraocularly.
• Multi-dose preparations : Multidose preparations contain a suitable antimicrobial
preservative in appropriate concentrations except in cases where the preparations
themselves have adequate antimicrobial properites.
Multidose preparation should normally not exceed 30 mL.
19. INTRAVENOUS INFUSIONS
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• Intravenous infusions are sterile, pyrogen-free aqueous solutions or
emulsions with water as continous phase, usually prepared to be isotonic.
• They are intended for administerd in large volumes (usually more than
100 mL) and od not contain any antimicrobial preservatives.
• On visual inspection emusions for intravenous injection should show no
evidence of phase separation.
20. POWDERS FOR INJECTIONS
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• Powders for injections are sterile, pyrogen-free solid substances (including freeze-dried
materials), distributed in their final containers and which, when the prescribed volume
of the appropriate sterile liquid is added, rapidly form either clear and practically
particle - free solutions or uniform suspensions.
• After dissolution or suspension,comply with the requirements for injections or
intravenous infusions, as appropriate.
21. IMPLANTS
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• Implants are sterile solid preparations containing one or more active
ingredients.
• They are of a size and shape suitable of parenteral implantation and provide
release of the active ingredients over an extended period of time.
• They are presented in individual sterile containers. All requirements for these
specialized dosage forms are given in the individual monographs.
23. SOLUTIONS
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A solution is a liquid preparation that contains one or more soluble chemical
substances dissolved in a specified solvent.
Large quantity component- solvent , small quantity component- solute.
Aqueous system:
• Compound dissolved - ionisable electrolytesand organic substances like
aldehydes, alcohols, ketones and amines.
• Compound undissolved- Non Polar compounds
Non - Aqueous system:
• These are anhydrous, nonpolar vehicleslike fixed oils.
24. IDEAL PROPERTIES OF SOLVENTS
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• SOLUBILITY- Therapeutically active compounds of parenteral route range in
properties frompolar to non polar thus solvents with complementary properties are
employed.
Example- Digitalis glycosided solubilize in 40% ethanol in water solution.
• TOXICITY- solvent be of minimum toxicity to body tissue.
Example - Testosterone is soluble in ether but cannot be used alone due to its high
irritant nature.
• pH- Stability is markedly affected by pH of solution.
Example- Epinephrine in parenteral solution - stable at pH < 3 Atropine sulphate is
stable at pH 3-4.
• DEGRADATION REACTION - water is prone to degradative reactions such as
hydrolysis, oxidation etc. thus appropriate measures can be employed.
25. SUSPENSIONS
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• Solid content- 0.5% to 5.0% (30% for antibiotic preparations)
• Administered usually by subcutaneous or intramuscular route
• Partcile size less than 5 micrometre (uniform particle size is necessary)
Formulation of Suspensions:
• Sterile vehicle and powder - aseptic combination
• Stabilizing Agents- Surface Active Agents- Polysorbate 80,Lecithin
Protective Colloid - Sodium CMC, Acacia ,Gelatin
Electrolytes- Mono sodium citrate
26. EMULSIONS
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• An emulsion is a heterogeneous dispersion of immiscible liquid in another,droplet size (1-
5 microns)
• The density difference of the two phases is kept as low as possible.
• Emulsifiers like lecithin, oxyethylene-oxypropylene polymer, gelatin, methyl cellulose
have been employed.
• Parenteral emulsion are rare because it is necessary and difficult to achieve stable droplet
of less than 1micron to prevent emboli in blood vessels, which is difficult to prepare for
such a preparation.
• Very limited selection of emulsifier and stabilizers is there to choose from.
• Administered through : IV, IM route
• Example- Emulsion of natural vitamin K1 has been stabilized with lecithin.
27. DRY POWDERS
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It is formulation of lypophilized or freeze- dried powders that must be reconstituted with
some suitable solvent to make a liquid formulation before being withdrawn form the vial.
• To overcome the instrinsic instability of the drug in the aqueous medium this formulation
is employed.
• The solid residue after freeze drying must have following characteristics:
• Uniform color and texture, solid matrix to maintain original volume , sufficient strength to
prevent crumbling during storage.
• The nature and amount of solids in solution determine:
• Eutectic Temperature, Sub zero temperature (at which frozen material will melt-
determines storage temperature.), rate of thermal and vapour transfer during drying.
• Salts used as solids: mono and dibasic sodium phosphates, NaCl, mannitol, sorbitol,
sucrose and gelatin.
28. CONCLUSION
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• The parenteral formulations are one of the most essential drugs systems in
pharmaceutical industry.
• Due to their direct administration in body cavities their sterlity and formulation
stablity is must follow criterion.
• Depending upon their administeration, they can be of varous types like injections,
implants infusions, etc.
• All the parenteral products must be prepared in aseptic conditions.
• The physical and chemical properties of all components of parenteral preparations are
thoroughly studied for any incompatibilities if possible.
