PARENTERAL DRUG DELIVERY Dr. Md. Harun Ar Rashid Head, Dept. of Pharmacy, NUB.

PARENTERAL DRUG PARENTERAL DRUG DELIVERYDELIVERY

Dr. Md. Harun Ar Rashid Head, Dept. of Pharmacy, NUB

Dr. Md. Harun Ar Rashid Head, Dept. of Pharmacy, NUB

PARENTERAL PRODUCTPARENTERAL PRODUCT

Sterile Products: Sterile products are dosage forms of

therapeutic agents that are free from micro-organisms or their spores.

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

1. Parenteral preparations2. Ophthalmic preparations - for the eye3. Otic preparations - for the ear 4. Nasal preparations - for the nose

& throat5. 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.

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

PARENTERALSpara: 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).

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.

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)

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.

BASIC REQUIREMENTS OF PARENTERAL PRODUCTS

1. Must be free from viable micro-organisms or their spores.2. Must be free from toxic components/pyrogens3. 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 < 1 μmho.

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.

PARENTERALS ARE ADMINISTERED BY:PARENTERALS ARE ADMINISTERED BY:

Physician Physician’s assistant Nurse

PARENTERALS ARE ADMINISTERED AT:PARENTERALS ARE ADMINISTERED AT:

HospitalsClinicsExtended care facilities

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)

Routes of Parenteral Administration

Intradermal (23)Intramuscular (20)

Intravenous (21)Subcutaneous (21)

Dermis

Intra arterial (20-22)

Vein

Artery

Muscle

Epidermis

Subcutaneous tissue

Parenteral Routes of AdministrationParenteral 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 injectionc. Peridural Injections

8. Intra-articular – joints

9. Intrasynovial – joint fluid

10. Intrapleural - lung

1. 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

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

1. upper arm, 2. the anterior surface of the thigh, and the 3. 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.

*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

3. Intramuscular (IM)3. Intramuscular (IM)

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

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:

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

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

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.

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 “Z”pattern 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

4. Intravenous Route (IV)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

Intravenous Route (IV)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

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)

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

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.

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.

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.

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

(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.

(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 won’t 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.g—localized anaesthetic

(b) Intra-cisternal injectionThey are given in between the first and second

cervical vertebrae. This route is principally used to withdraw

cerebrospinal fluid for diagnostic purposes.

8)Intra-articular route: Intra-articular injections are made into the synovial

fluid which lubricates the articulating ends of bones in a joint.

e.g—specially arthritis gout

– Given directly into the joints– 2 to 20 ml – 5 inch 22 gauge– Must be isotonic

Given:– Morphine– Steroids– NSAID’s– Antibiotics

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.