PARENTERAL DRUG DELIVERY

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PARENTERAL DRUG DELIVERY

Dr. Md. Harun Ar Rashid Head, Dept. of
Pharmacy, NUB
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PARENTERAL PRODUCT
Dr. Md. Harun Ar Rashid Head, Dept. of
Pharmacy, NUB
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• Sterile Products
• Sterile products are dosage forms of therapeutic
  agents that are free from micro-organisms or
  their spores.

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Based on the route of administration, sterile
products are classified into

• 1. Parenteral preparations
• 2. Ophthalmic preparations - for the eye
• 3. Otic preparations - for the ear
• 4. Nasal preparations - for the nose
  throat
• 5. Irrigating solutions - for
  washing wounds or
  abraded mucous membrane
• Parenteral Products Parenteral products are
  sterile dosage forms that are injected into body
  tissues (into internal body compartment) through
  one or more layers of skin or mucous
  membrane.Therefore, they must be exceptionally
  pure and free from physical, chemical and
  biological contaminants.

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• Definitions related to the topic
• -- Parenteral Products
• Sterilization Sterile Product
• Pyrogen
• SVP
• LVP
• Light Resistant Containers
• Well closed containers
• Tightly closed containers
• Single dose container
• Multiple dose container
• Hermetically sealed container

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• PARENTERALS
• para outside
• enteron intestine (i.e. beside the intestine)
• These are the preparations which are given other
• than oral routes.
• Injections
• These are
• Sterile,
• Pyrogen free preparations intended to be
  administered parenterally (outside alimentary
  tract).

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• Why Parenteral? Parenteral Route Is Used bcoz
• 1) Rapid action
• 2) Oral route can not be used
• 3) Not effective except as injection
• 4) Many new drugs particularly those derived from
  new development in biotechnologically can only be
  given by parenteral coz they are inactivated in
  GIT if given orally.
• 5) New drugs require to maintain potency
  specificity so that they are given by parenteral.

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• Advantages
• Quick onset of action
• Suitable for the drugs which are not administered
  by oral route
• Useful for unconscious or vomiting patients.
• Duration of action can be prolonged by modifying
  formulation.
• Suitable for nutritive like glucose
  electrolyte.
• Suitable for the drugs which are inactivated in
  GIT or HCl (GI fluid)

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• Disadvantages
• Once injected cannot be controlled (retreat)
• Injections may cause pain at the site of
  injection
• Only trained person is required
• If given by wrong route, difficult to control
  adverse
• effect
• Difficult to save patient if overdose
• Sensitivity or allergic reaction at the site of
  injection
• Requires strict control of sterility non
  pyrogenicity than other formulation.

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• BASIC REQUIREMENTS OF PARENTERAL PRODUCTS
• 1. Must be free from viable micro-organisms or
  their spores.
• 2. Must be free from toxic components/pyrogens
• 3. Must be free from chemical contaminants.
• 4. Must be free from foreign particles such as
  dust, fibres.
• 5. Safety level of all the ingredients should be
  same and every means of safety should be ensured
  including packaging material.
• 6. The pH of the product should be strictly
  maintained. Adequate buffers should be used.
• 7. Water used in parenteral products must be
  inert/sterilized.
• 8. Isotonicity of the product must be maintained.
• 9. Container of products must be free from
  pyrogens.
• 10.Water for injection should have conductivity lt
  1 µmho.

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• Necessities of Parenteral preparations
• Sterility (must)
• Pyrogen (must)
• Free from particulate matter (must)
• Clarity (must)
• Stability (must)
• Isotonicity (should)
• Solvents or vehicles used must meet special
  purity and other standards.
• Restrictions on buffers, stabilizers,
  antimicrobial preservative. Do not use coloring
  agents.
• Must be prepared under aseptic conditions.
• Specific and high quality packaging.

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• PARENTERALS ARE ADMINISTERED BY

• Physician
• Physicians assistant
• Nurse
• PARENTERALS ARE ADMINISTERED AT

• Hospitals
• Clinics
• Extended care facilities

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6 hypodermic needles on luer).
connectors from top to
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• 6 hypodermic needles on luer connectors from top
  to bottom 26G 1/2" (0.45 12mm) (brown), 25G
  5/8" (0.5 16mm) (orange), 22G 1¼" (0.7
  30mm) (black), 21G 1½" (0.8 40mm) (green),
  20G 1½" (0.9 40mm) (yellow), 19G 1½" (1.1
  40mm) (white)

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Routes of Parenteral Administration
Subcutaneous (21)
Intravenous (21)
Intramuscular (20)
Intradermal (23)
Intra arterial (20-22)
Epidermis
Dermis
Vein
Artery
Subcutaneous tissue
Muscle
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Parenteral Routes of Administration

• 1. Intradermal skin
• 2. Subcutaneous or Hypodermis
• under the skin
• 3. Intramuscular muscles
• 4. Intravenous veins
• 5. Intra-arterial arteries

6. Intracardiac heart 7. Intraspinal spinal
column a. Intrathecal or subarachnoid
injection b. Intra-cisternal injection c.
Peridural Injections 8. Intra-articular
joints 9. Intrasynovial joint fluid 10.
Intrapleural - lung
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• Intracutaneous or Intradermal
• also called as diagnostic testing
• administrated into the skin between
  the epidermis and dermis
• usual site is the anterior surface of
  the fore arm
• needle is inserted horizontally with
  the bevel facing upward
• 0.1 0.2 ml due to poor vascularity
  of the site
• short 3/8 inch, 23 to 26 narrow
  gauge needle
• Should be isotonic
• Given
• Diagnostic agents for immunity and allergy
  test e. g test for penicillin

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2.Subcutaneous or Hypodermis(SC SQ Sub Q)

• Utilized for
• the injection of small amounts of medication or
  of drugs beneath the surface of the skin of the
• upper arm,
• the anterior surface of the thigh, and the
• lower portion of the abdomen.
• The site of injection is usually rotated when
  injections are frequently given, as with daily
  insulin injection.
• The maximum amount of drug given SC is about 1.3
  mL
• Amounts greater than 2 mL will most likely cause
  painful pressure.
• - ½ to 1 inch. 23 gauge needle or smaller needle
  is used
• 
  Continued.

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• The route is not used for aqueous suspensions or
  oily suspension and fluids.
• It is usually used for self-medication by the
  patient
• Upon insertion, if blood appears in the
  syringe, a new site should be selected.
• Irritating drugs and those in thick
  suspension may produce
• - induration, sloughing, or abscess and may be
  painful. Such preparations are not suitable for
  subcutaneous injection.
• Given Vaccines, Insulin, Scopolamine,
  Epinephrine

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3. Intramuscular (IM)
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• The route is used for aqueous and oily
  suspensions and oily solutions,
• Reduce Pain and irritation (subcutaneously),
  blockage of small blood vessels (intravenously)
  occur.
• Intramuscular injections of drugs provide effects
  that are less rapid, but generally of greater
  duration than those obtained from intravenous
  administration

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• IM are performed deep into the skeletal
• muscles.
• The point of injection should be as far as
  possible from major nerves and blood vessels.
• Injuries to patients from IM injection usually
  are related to the point at which the needle
  entered and where the medication was deposited.
• 
  Continued

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• Such injuries include
• 1. Paralysis resulting from neural damage
• 2. Abscesses
• 3. Cysts
• 4. Embolism
• 5. Hematoma
• 6. Sloughing of the skin
• 7. Scar formation

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• Principle sites
• Gluteal (buttocks)
• Deltoid (upper arms)
• Vastus lateralis (lateral thigh)
• Adult upper outer quadrant of the gluteus
  maximus
• Infants gluteal area is small, composed
  primarily fats not muscle, so not recommended.
• Infants and Young children deltoid, muscles of
  the upper arm or the midlateral muscles of the
  thigh

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• Volume of Administration
• 0.5 to 2 ml sometimes upto 4 ml
• 1 to 1.5 inch 19 to 22 gauge needle is used
• Preferably isotonic
• To avoid staining it must be injected only
  into the muscle mass of the upper outer quadrant
  of the buttock.

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• The skin is displaced laterally, then needle
  inserted and syringe aspirated, and injection
  performed slowly and smoothly. The needle is then
  withdrawn and the skin release. This create a
  Zpattern that blocks infiltration of medication
  into subcutaneous tissue.
• The Z-Track Injection techniques is useful for IM
  injections of medications that stain upper
  tissue.
• Examples
• Iron dextran injection irritate tissues
• Diazepam (Valium) by sealing in the lower
  muscle

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4. Intravenous Route (IV)

• Advantage
• May be a life-saving procedure because of the
  placement of the drug directly into the
  circulation and the prompt actions which ensues.
• Disadvantage
• Once the drug administered, it cannot be
  retrieved.
• In the case of adverse reaction to the drug, for
  instance, the drug cannot be easily removed from
  the circulation.
• Precautions
• Strict aseptic precautions must be taken at all
  times to avoid risk of infection.
• The syringes and needles used must be sterilized
  and to the point of entrance must be disinfected
  to reduce chance of carrying bacteria from the
  skin into the blood via the needle

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• Intravenous Route (IV)
• - Administered into the vein 1 to 1000 ml
• - 1 inch , 19 to 20 gauge needle with injection
  rate 1ml / 10 sec. for volume upto 5 ml 1 ml/
  20 sec.for volume more than 5 ml.
• - Great care must be taken to prevent
  overdosing or underdosing
• Given
• Aqueous solutions
• Hydro alcoholic solutions
• Emulsions
• Liposome

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• IV infusion of large volume fluids (100- 1000 ml)
  has become increasingly popular. This technique
  is called as Venoclysis.
• This is used to supply electrolytes nutrients
  to restore blood volume to prevent tissue
  dehydration.
• Combination of parenteral dosage forms for
  administration as a unit product is known as an
  IV admixture.
• Lactated Ringer Injection USP
• NaCl Injection USP (0.9 ) (replenish fluid
  electrolyte)
• Dextrose Injection USP (fluid electrolyte)

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• Intravenous fat emulsions
• Intralipid, 10,20,30
• Clintec
• Liposyn 11,10, 20
• Abott Liposyn 111, 10,20,30
• as a source of calories and essential fatty acids
  for patients requiring parenteral nutrition for
  extended period, usually more than 5 days.
• The product contains up to
• 30 soybean oil emulsified with egg yolk
• phospholipids in a vehicle of glycerin in
  water injection

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• The possibility of thrombus formation
• induced by the touching of the wall of the vein
  by the catheter or needle.
• Thrombus
• is a blood clot formed within the blood vessel
  (or heart) due usually to a slowing of the
  circulation or to an alteration of the blood or
  vessel wall.
• Once such a clot circulates, it becomes an
  Embolus
• carried by the blood stream until it lodges in a
  blood vessel, obstructing it, and resulting in
  blockage or occlusion referred to as an Embolism.

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• NOTE
• Not only are the injectable solutions sterile,
  syringes, needles must also be disinfected to
  reduce the chance of carrying bacteria
• A backflow of blood into the administration set
  or syringe indicates proper placement of the
  needle in the vein
• Intravenous drugs ordinarily must be aqueous
  solution
• they must mix with the circulating blood and not
  precipitate from solution. Such an event can
  lead to pulmonary micropillary occlusion and
  blockage of blood flow.

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• 5.Intra-arterial(IA)
• Direct into the artery
• 2 to 20 ml
• 20 to 22 gauge
• Solutions emulsions can be administered
• Given
• Radio opaque media
• Antineoplastic
• Antibiotics
• Intra-arterial injections are similar to
  intravenous injection and used occasionally for
  an immediate effect in a peripheral organ.
• Such as - To improve circulation to the
  entremities when arterial flow is restricted
  by arterial spasm or early gangrene.
• Example-Tolazoline HCl, peripheral
  vasodilatorsis sometimes used by this route.

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• Intracardial
• Directly given into the heart
• 0.2 to 1 ml
• 5 inch , 22 gauge needle
• This route is used for emergencies condition only
  when drugs are given directly into muscle on
  ventricles.
• Example-
• - Stimulants, such as adrenaline or
  isoprenaline sulphate.
• - Cadiotonics
• - Calcium salts as a calcium channel blockers

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• (7)Intra-spinal route
• These routes involve access into or around the
  spinal cord. Single dose injections, not greater
  than 20 ml are used.
• Spinal cord is enclosed in three coats
• The outer one is known as the dura mater,
• The middle one as the arachnoid and
• The inner one as the pia mater.
• The subarachnoid space lies between the arachnoid
  and
• pia mater and contains C.S.f.

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• (a)Intrathecal or subarachnoid injection
• Intrathecal injections are made into the
  subarachnoid space.
• This route is used for spinal anesthetics and
  antibiotics such as Streptomycin in the treatment
  of tubercular meningitis (Mycobacterium T.B)
• Specific gravity of such injection should
  maintain as that of C.S.f so that it wont be
  diffuse into the brain.
• (c) Peridural Injections
• These are made into the peripheral space which
  located between the durameter and the inner
  aspect of vertebrae. This space extends through
  out the full length of spinal cord.
• e.glocalized anaesthetic

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• (b) Intra-cisternal injection
• They are given in between the first and second
• cervical vertebrae.
• This route is principally used to withdraw
  cerebrospinal fluid for diagnostic purposes.

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• 8)Intra-articular route
• Intra-articular injections are made into the
  synovial fluid which lubricates the articulating
  ends of bones in a joint.
• e.gspecially arthritis gout
• Given directly into the joints
• 2 to 20 ml
• 5 inch 22 gauge
• Must be isotonic
• Given
• Morphine
• Steroids
• NSAIDs
• Antibiotics

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• 9. Intrapleural
• Given directly into the pleural cavity or lung
• Used for fluid withdrawal
• 2 to 30 ml
• 2 to 5 inch, 16 to 22 gauge needle
• Given
• Narcotics
• Chemotherapeutic agents
• (10) Intra-bursal route
• Intra-bursal injections are given into the
  bursare which are small sacs of fluids between
  movable parts such as tendons and bones.