PARENTERAL DRUG DELIVERY SYSTEM

Wan Maznah Wan Ishak

Contents

▪ Introduction
▪ Common route of parenteral delivery
▪ General considerations of parenteral drug delivery systems
▪ Advantages and disadvantages of parenteral drug delivery
 Introduction
• Parenterally “par” means outside “enteral” means intestinal (beside the
intestine).
• Parenteral drug administration refers to drugs given by routes other than
the digestive tract. The term parenteral is usually used for drugs given by
injection (small volumes) or infusion (large volumes).
• The parenteral route is the fastest and the second commonest route of
drug administration.
• The most important and most frequently used parenteral routes are
intravenous route (IV), intramuscular route (IM) and subcutaneous
(SC) route, respectively.
• Some examples of parenteral drugs include epinephrine, insulin, and IV
infusions.
Parenteral Route of drug delivery
Most common route
• Intravenous (in a vein)
• Intramuscular (in a muscle)
• Subcutaneous (under the skin)
• Intradermal ( into the skin)
Others less frequent parenteral routes are
• Intraperitoneal (into the peritonium)
• Intraarterial (arteries )
• Intrathecal (around the spinal cord –spinal fluid)
• Intraspinal (spinal cord column)
• Intrasynovial (joint fluid area)
• Intraarticular (joints)
1. Intravenous (IV)Route
• Administration of the drug directly to the veins (systemic circulation) or through an
IV catheter.
• Route produces fast onset of action
• No lag time or absorption phase for the drug
• Usually given slowly
• Two types

IV DRIP or Drug is injected into the veins over a

IV INFUSION sustained period and larger
volume are administered.

Drug is injected into the veins over a

IV BOLOUS shorter period and small volume
are administered.

Bioavailability of drug is 100% when administered intravenously.

Drugs typically given by IV Route
Many different types of medications can be given by IV.
Examples:
• Analgesic
• General Anesthetic
• Antiviral agents
• Antibiotics
• Immunosuppressive agents
• Antifungal agents
• Antihypertensive agents
• Vasodilators
• Chemotherapy drugs
Advantages of IV route of drug delivery
▪ Rapid onset of action
▪ Choice of route in case of emergency
▪ Drugs that are destroyed in GIT (insulin) can be used by this route.
▪ It avoids degradation of drug in Liver (First pass effects)
▪ Best for unconscious patients
▪ Irritating and non-isotonic solutions can be administrated by this route
▪ Large volume can be injected
Disadvantages of IV route of drug delivery
▪ The drugs administered by this method have short duration of
action
▪ Skill staff is required for administration
▪ Once administered its difficult to reverse
▪ Expensive
▪ Painful
▪ If injected too fast, it may drop blood pressure
▪ Self administration is not possible.
2. Intramuscular (in a muscle)
▪ Intramuscular (IM) injections are administered into
muscle tissue below the dermis and subcutaneous
tissue.
• Angle : 90
• This route is used in administering aqueous or
oleaginous suspensions or solutions.
• A volume of 5-10 mL can be given at a time
• IM can be injected into Upper arm, Thigh, Buttock
• Relatively longer onset of action than IV injections
(generally 30 minutes)
• Rate of absorption depend on formulation and site of
injection
• Oil based is slow
• Water –based (aqueous solutions ) is fast
Formulation and delivery strategies for IM
• For water-insoluble drugs
• solubilized in solvents such as propylene glycol and mineral oil for
injection
• These non-aqueous vehicles stay at the site of injection and release the
drug slowly which results in prolonged serum drug concentrations and a
longer duration of action
• For water-soluble drugs
• dissolved in aqueous vehicles and prepared as solutions for injection
• IM injections given into the deltoid muscle in the arm absorbed faster
than gluteal injections due to increased blood flow in the deltoid muscle
Drugs typically given by IM Route
▪ The most common medications given by IM route include Paracetamol,
Diclofenac
▪ Antibiotics- penicillin G, benzathine penicillin, streptomycin.
▪ Biologicals- immunoglobins, vaccines
▪ Hormonal agents- testosterone, medroxyprogesteron
Advantages & Disadvantages of IM
drug delivery
Advantages
• Absorption rate is more rapid as compared to oral route.
• Precise control of dose and administration rate.
• Suitable for injection of drug in aqueous solution (rapid action) and drug in
suspension or emulsion (sustained release).
Disadvantages
• Pain at injection sites for certain drugs.
• Self administration is not possible.
• Larger volume cannot be administered.
• Aseptic conditions are needed.
3. Subcutaneous (SC) Route
▪ SC injections are administered beneath the surface of
the skin, between the dermis and muscle.
▪ Also referred as hypodermic injection
▪ The drug is injected into the subcutaneous tissues of the
thigh, abdomen and arm, e.g., adrenaline, insulin, etc.
▪ Very small volume such as 2 mL or less is injected via
this route.
▪ Drugs absorbed slower rate than IM injections because
there is less blood flow to the fatty tissue below the skin
than to the muscle

Self administration is possible ; such as Insulin, vaccines,

heparin, growth hormone
Advantages and disadvantages SC
drug delivery
Advantages
• Self-administration is possible because deep penetration in not needed (e.g.,
insulin).
• Less expensive than IV therapy
• Avoid fast pass effects

Disadvantages
• It is suitable only for non-irritant drugs.
• Drug absorption is slow; hence it is not suitable for emergency purpose use.
Others Route
1. Intradermal Route
▪ Intradermal injections (ID) are injections
administered into the dermis, just below the
epidermis.
▪ Longest absorption time.
▪ Very small volume injection (0.1 mL)
▪ Used for sensitivity tests, such as TB,
allergy, and local anesthesia tests.
2.Intraarterial Route

• Intraarterial means drug administered within or into the artery or

arteries.
• It is used
• to reduce drug exposure to the systemic circulation
• to increase drug concentrations
• Chemotherapeutic drugs e.g. :-Anticancer agent for drug targeting to
a particular organ
• Disadvantages it has been associated with embolism and drug toxicity
3. Intracardiac
Injections are given directly into the heart
muscles or ventricles.
e.g. : Antiarrthymatic drugs -Quinidine,
propranolol

4. Intraspinal

• Drugs are given directly into ground of

spinal cord, spinal column and especially
the vertebral canal.
• e.g. :- Anaesthetics drugs:- lidocaine,
propofol, epidural
• Clinical effects are more localized to the
spinal cord
5. Intracerebral
Drugs are introduced or administered
into the cerebrum.
e.g. :- Adrenaline, amphetamine

6. Intraocular
Drug are administrated by entering the
eyeball and around of eyes.
e.g. :- Avastin, carbacol

7. Intraperitoneal
Infusion or injection into the peritoneum e.g., peritoneal dialysis
in case of renal insufficiency.
General considerations of parenteral
drug delivery systems

• They must be free of pyrogens.

• Pyrogens or fever-producing substances may be found in parenteral
formulations which can lead to complications after the formulation is
injected.
• They must be sterile and free from of all microbial organisms.
• They must be isotonic. Tonicity-adjusting agents decrease that
hemolysis of blood cells and reduce pain and irritation at the injection
site.
• Strict aseptic precaution must be taken all time to avoids risk of
infections
• Calculate correct amount of medication to administer
General considerations of parenteral
drug delivery systems
▪ Select appropriate equipment
▪ Administration of drug by trained personnel.
▪ Proper angle of insertion and removal of needle is required to
reduce pain during injection.
▪ Should maintain administration flow rate of drug.
▪ Single use syringe and needle must be used with each patient
▪ It should be more careful so that injection must be free of air
bubbles and particulate matter.
General Categories of Injectables
• Injectables can be divided into five major categories
➢ Injection
➢ For injection
➢ Injectable Emulsion
➢ Injectable Suspension
➢ For Injectable Suspension
1. Injection
• Are liquid preparation of drug substances or solutions
• Can be aqueous solutions or solutions in oil
• Aqueous solution
• Rapid onset of action (30 min)
• Peak between 1 – 3 hours
• Duration of effect is 8 hours
• Eg, human insulin of recombinant DNA
• Water insoluble drugs maybe formulated as solutions by dissolution in
vegetable oils
• Duration of action is longer
• May cause embolism, thus should be injected IM, not IV
• Eg, estradiol cypionate
2. For Injection
• Are dry solid formulation, but on addition of suitable vehicles
yield solutions that conform all respects to injection
requirements
• Eg, cefuroxime for injection

3. Injectable Emulsion
• Are liquid preparations of a drug substance dissolved or dispersed in a suitable
emulsion medium
• IV emulsions usually lipid-soluble drugs dissolved in an oil-based vehicle for
injection
• An emulsion is an effective delivery system for solubilization of water-insoluble drugs.
• It produces a dosage formulation with increased stability and sustained-release
characteristics
• Emulsion release drug at a slower rate than solutions but more promptly than IM
• Eg, Propofol
4. Injection Suspension
• Are liquid preparation of solids suspended in a suitable liquid medium
• A suspension is a dispersion system in which the undissolved solid drug is
present in a sterile aqueous vehicle
• Suspensions is used for unstable drugs in solution
• Drugs in suspension are generally more stable and can be administered by IM,
SC and intra-articular injection
5. For Injection Suspension
• Are dry solid formulations that on addition of a suitable vehicle, yield a
dispersion conforming all respects to the requirements of an injectable
suspension
• Drug that are poorly soluble in water and unstable provided as “For injectable
suspension” formulations
• The drug is supplied as dry powder with suspending agents and reconstituted
in appropriate vehicle immediately before injection
• Eg, Azacitidine
Advantages of Parenteral Drug Delivery
▪ It can be used in patients who are unable or refuse to take
medications by mouth
▪ Rapid and complete absorption of drugs from systemic circulation
takes place if drug is administered IV as a solution
▪ First-pass hepatic metabolism is avoided, which leads to improved
bioavailability for drugs that undergo significant first-pass metabolism
after oral administration.
▪ Smaller doses can be used with IV administration than with oral
administration
Advantages of Parenteral Drug Delivery
• IV administration of drugs has been shown to provide a more
predictable pharmacokinetic and pharmacodynamic profile for drugs
than oral administration
• The route for parenteral delivery can be tailored to the needs and
condition of the patient.
• Direct injection of the drug by the IV route is beneficial in
emergency situations when the need for therapeutic action is
immediate.
• For slower onset and a longer duration of action, drugs can be
administered IM
Disadvantages of Parenteral Drug Delivery
▪ Aseptic precautions must be followed to avoid contamination and
minimize the risk of infection when the drug is administered
▪ Most often, parenterally delivered drugs are administered by trained
health care professionals in clinics and hospitals. This is more
inconvenient and costly than self-administration of drugs
▪ Manufacturing is also more costly than the manufacture of
conventional tablets and capsules
Disadvantages of Parenteral Drug Delivery
▪ Once drugs are injected IV, they cannot be removed easily from
bloodstream.
▪ This can be a problem if an incorrect dose or drug is administered,
because adverse effects can result.
▪ Dialysis or hemofiltration can be used to remove excess drug, but these
are complicated procedures and can cause discomfort to the patient
▪ Injections may be accompanied by pain and infection at the site of
injection