Download Lecture 5 V- Parenteral administration

Lecture 5
V- Parenteral administration
- Definition:
The term parenteral refers to the administration of drugs other than by
elementary tract.
 Injections are sterile drugs formulations in a suitable vehicle with
or without added substances.
 They can be packed up as single- dose unit (ampoules) or
multidose unit.
 Injections may be suspension, emulsion, or solution.
- Advantages of parenterals:
1. Immediate response e.g. cardiac arrest, asthma.
2. Used for drugs which destroyed by digestive secretions or not
effective orally, e.g. hormones, insulin.
3. Used for local effect, e.g. local anesthetics in dental therapy.
4. Suitable for unconscious patients
5. Correct fluid and electrolyte disturbances.
6. Provide prolonged drug actions e.g. long acting penicillin.
7. Blood transfusion.
- Disadvantages:
1.
2.
3.
4.
5.
Pain upon injection.
Thrombosis at injection site.
Infection of m.o., toxins.
Local muscle damage due to large bolus of drug.
Accidental striking of injection in to peripheral nerve, resulting in
peripheral nerve palsy with or without sensory damage.
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- Types of injection preparations:
1. Solutions of medicaments.
2. Dry solid intended to be dissolved in suitable vehicle before use
e.g. hypodermic solution tablets
3. Suspensions
4. Emulsions
- The formulation of injections involves careful consideration of the
following factors:
1. The route of administration
2. The volume of injection
3. The vehicle in which the medicament is to be dissolved or suspended
4. The osmotic pressure of solution
5. The need for a preservative
6. The hydrogen ion concentration of solution
7. Stability of the medicaments
8. The weight per ml –when the injection is used for spinal anesthesia
Routes of administrations:
1. Intracutaneous or intradermal injection (IC ,ID)
2. Subcutaneous or hypodermic injection (S.C)
3. Intramuscular injection (I.M.)
4. Intravenous injection (I.V.)
5. Intra-arterial injection (I.A.)
6. Intracadiac injection
7. Intrathecal injection (I.Th.)
8. Intra-articular injection
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1)- Intracutanous or Intradermal Injections (I.C. or I.D.) :
- Are made into the skin, between the inner layer or dermis & the outer
layer or epidermis.
-The volume that can be injected intradermally usually 0.1 to 0.2 ml
-This route is used mainly for diagnostic investigations of immunity &
allergy.
(2)- Subcutaneous or Hypodermic injections (S.C.) :
- Are made under the skin, into the subcutaneous tissue.
-The volume injected is 1 ml or less into the upper arm.
-This is the most popular route because it is convenient for patients &
doctors.
(3)- Intramuscular Injections (I.M.) :
- Are made into the muscle
-The needle passing through the skin subcutaneous tissue & then the
membrane enclosing the muscle.
-The volume is between 2-4 ml
-Oily suspensions & oily solutions cannot be given subcutaneously
because they cause pain & irritation or (I.V) because blockage of small
blood vessels might occur. I.M. route is used for these administrations
-Intramuscular injections, except in small volume are very painful unless
administered slowly.
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(4)- Intravenous Injections (I.V.) :
- Are made into a vein & introduced directly into blood stream.
-The volume injected from 1ml or less to 500 ml or more.
- Small volumes are given when a very rapid effect is required as for
anesthetic (e.g. thiopentone).
-Large volume injections often called perfusion or infusion fluids are
needed to replace fluids lost from the circulation (shock, severe burns,
vomiting, diarrhea, hemorrhage).
(5)- Intra -arterial Injections (I.A.) :
- Are similar to I.V. injections & are used for immediate effect in a
peripheral area ,for example :to improve circulation to the extremities
when arterial flow is restricted by arterial spasm.
- e.g.: Tolazoline Hydrochloride is peripheral vasodilators is used by this
route.
(6)- Intracardiac Injections:
- Are given into muscle heart in an emergency ,e.g.: as stimulant
following cardiac arrest ,(Adrenaline or Isoprenaline sulphate).
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7- Intrathecal injections (I.th.)
- Are made into the subarachnoid space that surrounds the spinal cord.
-The injection volume is less than 20 ml and the route is used for spinal
anesthetics (e.g. Amethocaine HCL) and antibiotics (e.g. streptomycin
sulphate in the treatment of tubercular meningitis).
- Also for withdrawn the cerebrospinal fluid for diagnostic purpose.
8- Intra-articular injections:
- This type is made into synovial fluid that lubricates the bones in joint.
- For examples; anti-inflammatory drugs (hydrocortisone acetate) in the
case of arthritis, rheumatism.
- Solutions or suspensions are administered.
Volume of injection
- The volume of injection depends on:
1- The solubility of the medicament.
2- Particular route prescribed.
- Intracutanous or Intradermal Injections (I.C. or I.D.) injections must be
of very small volume because they do not disperse quickly from their
relatively non-vascular site (even a fraction of milliliter remains as a
small blister for sometime after injection).
- Only the I.V. route is suitable for very large volumes because the
injection being allowed to drip slowly into a vein from a bottle
suspended over the patients bed and produce infusion.
- Large volume must be made isotonic.
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-The volume must be convenient to administer.
- More than 20 ml is unsuitable for injection by a syringe.
The vehicle
- It is an essential part of injection.
-It must be:
1- Non-toxic.
2- Pharmacologically and therapeutically inert.
3-Maintain the drug solubility.
4- Non-sensitizing.
- The vehicle may be: aqueous or non-aqueous.
A- Aqueous vehicle:
- Water is used as a vehicle for most injections because:
1- Tolerated well by the body.
2- Safe.
3- Easy to be administered.
- But it is not the vehicle of choice for drugs that having low water
solubility.
- The water for injections must be:
1- Free from pyrogens.
2- Free from carbon dioxide.
3- Free from dissolved air.
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B. Non-aqueous vehicle:
- Non-aq. Vehicle is necessary for the preparation of parenteral product
to fulfill certain requirement which is impossibly obtained by the use of
aqueous vehicle such as:
1. If the medicament is insoluble or slightly soluble in the
water.
2. When a depot effect is desired like in the cases of
progesterone, testosterone propionate and estradiolbenzoate (are insoluble or slightly soluble).
3. When an oil medium is more suitable for a diagnostic
purposes e.g. propyliodone which is oily suspension for Xray of the respiratory tract (because this is less irritant than
aq. Suspension).
- The non-aqueous vehicle must be:
- Safe and not interfere with the therapeutic efficacy of
preparation.
- The non-aqueous vehicles of common use in parenteral
formulations are:
1. Oils and esters.
2. Alcohols.
3. Propylene glycol.
 Disadvantages of oily vehicle:
1. Very viscous in cold weather.
2. Cause pain on injection.
3. Make syringes and needles difficult to clean.
4. Cause thrombosis, therefore oily injection must be labeled
for I.M. use only.
 The most commonly used oils:
Arachis oil – sesame oil – cotton seed oil – maize oil.
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- The need for a Preservative:
 This for multi-dose injections.
 The reason for use preservative:
a) The danger in introducing bacteria into injection and the rapidity
with which they can multiply. (Preventing the growth and
multiplication of M.O.)
b) For prevent the destructive action with some bacteria and moulds
(e.g. penicillin is inactivated by penicillinase enzyme secreted by a
number of bacteria).
Bactericides suitable for aqueous preparations:
1. Must have the ability to prevent the growth or kill contaminated
organism.
2. Compatible with medications.
3. Low absorption rate into rubber.
- For I.V. Large volume, the bactericides must not be included (if the
volume exceeds 15 ml). Due to the risk of administrating of toxic
dose (not be used in infusion fluid).
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II- (Sustained or extended or prolonged)
Release Medications


Prolonged – release medication is:
A dosage form containing more drug than a conventional dosage
form and releasing the drug more slowly over a period of hours or
days.
The prolonged – release medications (dosage forms) offer
several important advantages over immediate (conventional)
dosage forms of the same drug:
1) Allows for sustained therapeutic blood level of the drug
provides a prolonged response in patient.
2) Patient convenience which lead to better patient
compliance (because the dosage interval is longer
the
patient need not interrupt sleep)
3) Patient may have an economic benefit in using (sustained),
prolonged – release drug product:
 A single dose of prolonged product might cost less
than an equivalent drug dose given several times a
day in rapid release tablets.
 For patient under nursing care, the cost of nursing
time required to administer medication is decreased
if only one drug dosage is given to patient each day.

Sometimes, there is no rationale for formulating of some drugs
in prolonged – release medications.
e.g.: chlorpheniramine which has:
1) Long elimination half – life and thus;
2) Duration of pharmacologic activity is long
3) Minimal fluctuations of blood conc. are observed after
multiple doses.
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
The prolonged release medication minimizes toxicity and decrease
adverse effects – provide patients with more convenience and
thus better compliance.

Disadvantages of prolonged – release – medication:
1) If the patients suffer from an adverse drug reaction or become
accidently intoxicated, the removal of drug from the system is
more difficult than with a rapid (conventional) – release
medications.
2) With orally administrated prolonged – release drug products,
erratic or variable drug absorption might occur due to the
various interactions of drug with the contents of GI tract and
the change of GI motility.
3) The formulation of prolonged release drug products for drugs
usually given in large doses (> 500 mg) in conventional dosage
forms may not be practical.
- Because the prolonged release medication may contain two or more
times the doses given in more frequent intervals and the size of
prolonged formulation would be quite large ( too large for the
patient to swallow).
- The prolonged release dosage form contains the equivalent of two
or more conventional drug doses given in a conventional dosage
form.
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- Therefore the failure of the prolonged release dosage form lead to
“Dose Dumping”.
Dose dumping is defined as:
The release of more than the usual fraction of drug or the release
of drug at a greater rate. The Potentially adverse plasma level may
be reached.
- Two Problems occur if the enteric coating or delayed drug
product is poorly formulated:
1- The enteric coating might not prevent early release of the
drug & the drug is degraded in stomach or cause irritation
to the gastric mucosal lining.
2- The enteric coating may fail to dissolve at the proper site &
the tablet may be lost prior to drug release.
Types of prolonged (extended, sustained)
Release products:
1- Pellet –type sustained release preparation:
- It is also called bead – type preparation.
 The beads are prepared by coating drug powder on to
preformed cores called: nonpareil seeds.
 The nonpareil seeds are made from slurry of starch,
sucrose & lactose.
 The preparation of cores is tedious.
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 The rough core granules are rounded for hours on a
coating pan & then classified according to Size.
 The drug – coated beads provide a rapid release for the
drug depending on the coating solution used in coating.
 Commonly, Sucrose solution provides a convenient way
of coating without impairing the rapid release of the
drug.
 Once the drug beads are prepared they may be further
coating with the protective coating to allow a sustained
or prolonged release of drug.
 A careful blending of beads may achieve any release
profile desired.
 A blend of beads coated with materials of different
solubility, may provide a means of controlling dissolution
of drug.
 Some products prepared in the form of bead blending to
provide two doses of drug in one formulation.
 For example: A blend of rapid – release beads with
some PH sensitive enteric coated material may provide a
second dose of drug release when reaches intestine.
 The pellet dosage form can be prepared as: Capsule and
Tablet
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 Formulation of the drug into pellet form may reduce
gastric irritation because the drug is released slowly over
a period of time and therefore avoiding high drug
concentration in the stomach.
Examples:
1. If thiophylline is administrated as a solution, so high conc. May
be reached in body due to rapid drug absorption and side
effect produced.
 Pellet dosage form allows drug to be absorbed
gradually, therefore reducing the incidence of side
effect by preventing high C max.
2. Indicated that the incidence of tachycardia was reduced in
prolonged - release bead preparation for bitolterol while the
bronchodilation effect was not reduced.
3. The formulation of potassium chloride in pellet or microparticle form reduced the gastrointestinal side effect (irritation
to GIT).
The main advantages of pellet dosage form are that:
 The pellets are less sensitive to effect of stomach
empting. Because there are numerous pellets within
capsules, some pellets will gradually reach the small
intestine and deliver the drug.
 Stomach empting is important in the formation of
enteric coated products. Enteric coated tablets may be
delayed for hours by presence of food in stomach while
Enteric coated pellets are unaffected by presence of
food.
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