ROUTE OF DRUG ADMINISTRATION

IN PRESCRIBING
(DRUG DELIVERY)

Dr. ARIFA MUSTIKA,dr.,M.Si

Departement of Medical
Pharmacology
Medical Faculty of Airlangga
University
Learning Objective

• To determine the most clinically

effective and safe methode
• To provide accurate and convenient
drug administration
• To obtain the desired therapeutic
response with minimum side effects
• To maximize patient compliance
 5 principle in prescribing

1. The right amount (dose)

2. Of the right medicine
(inggredient)
3. In the right dispensing form,
4. At the right route
5. and time of administration

To the right patient

?
The factors should be considered
in drug administration

Patients
Diseases
Drugs
patients

1. Age ( child, adult and geriatric)

2. General Condition ( conscious or unconscious,
uncooperative, nauseous, mentally impairment)
3. Social – Economic state (cost, convenience,
education)
diseases

1. Pathofisiology
2. Diseases state ( acute, chronic, staging)
3. Aim of therapy
– Local or systemic (localized drug administration has the
advantage of focusing high concentration of drugs at
desired site of action and minimizing systemic side
effects. The systemic approach is used when the target
tissue is inaccessible by direct administration or
application)
drug

1. Physico-chemical characteristics ( restrict its use

in only certain dosage form and/or by specific
routes of administration)
2. Pharmacokinetic (absorbtion, distribution,
metabolisme and excretion) influence
bioavailability, onset time, duration
3. Pharmacodynamic
Route of drugs administration

• Peroral • Otic
• Parenteral • Inhalation
• Topical/transdermal • Nasal
• Ophtalmica • Rectal
• Vaginal
 Peroral/ oral route

The oral route is the most

frequently, convenient and
economic used route for drug
administration.

Compared with others routes, the

oral route is the simplest and safest
because passage through the
existing track
mechanism
 Drugs administered orally either exert a
local effect on gastrointestinal system, or
absorbed through the mucosa into the
blood and lymphatic circulatory systems
and exert a systemic effect
 Absorbtion can occur in the mouth (buccal
and sublingual), small intestine, and to a
lesser extent, the stomach and large
intestine.
 Absorption was infuenced by gastric
emptying time, pH
 A few drugs are intended to dissolve in the
mouth for rapid absorption or for local effect
Advantages & disadvantages
Advantages
• Rapid absorption
• Rapid onset of action
• Convenients
• Relative low cost
• Controlled release can delay,
prolong, sustain or target drug
delivery (maintain drug plasma
concentration)
Disadvantages
• Relatively slow onset of action
• Patients who are unwilling or
unable to swallow
• Possibilities of irregular
absorption
• Destruction of certain drugs by
the enzymes and secretion of
gastrointestinal tract
• Interaction drugs with other
materials present in
gastrointestinal tract
Dosage form for oral route
Liquid dosage form Solid dosage form

• Solution • Tablet
• Suspension • Capsule
• Emulsion • Lozenges
• Aerosol • Pulveres (divided
powders)
• Pulvis (Powder)
• Controlled release
tablet/capsule
Parenteral
• An injection directly into an internal body
compartement or cavity to by pass the
protective effects of the skin and mucous
membrane ( breaking the barriers)
• It is critically that proper injection techniques
are used. An improper injection can cause
injuries to nerves, muscle, bone and blood
vessels.
• For be self-administered (patient is properly
instructed on the use of parenteral dosage
form and injection procedure)
Advantages & disadvantages

Advantages Disadvantages

• Rapid Onset of action • Pain

• Bioavailability • inconvenience
• Relative rapid • Negative patient
Pharmacology effect acceptance
• Unconscious • Special technique
• Gastrointestinal • “Malpractice”
disturbance
 The most common routes of parenteral
drug administration

Route site Ammount(

ml)
Intravenous Vein 0,5-50
Intraarterial Artery 10-50
Intraartikular Joints 0,1-3
Intracisternal Cerebrospinal column

Intrakardial Heart 1-10

Intradermal Dermis 0,01-0,1
Intraspinal Spinal column

Intraosseous Bone

Intrasinovial Joint fluid

Intrathecal Spinal fluid

Intramuscular Muscle 0,5-5

Subkutan Beneath the skin 0,5-1,5
 Dosage form for parenteral
drug administration
• Solution ( all products for parenteral drug
administration must be sterile and pyrogen free, in
the case of solutions, free of particulate matter)
• Suspension (cannot be administrated intravenously
because of possibility of insoluble particles blocking
the capillaries)
• Emulsion (usually of the oil in water type, particle
size < 5 µm)
• Dry powder (for unstable drugs, reconstituted as a
solution or suspension)
• Intraocular, intraspinal, intracisternal, and
intrathecal drug administration requires formulations
of the highest purity becaause of the sensitivity of
nerve tissue to iritant and toxic substance
TopiCal & Transdermal

Topical is route of drug administration through the

skin for local action
Transdermal is route of drug administration
through the skin for systemic drug delivery
Transdermal

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Dosage form

• liquid • Semi solid

– Solution – Gel
– Suspension – Unguentum
– Emulsion – Cream
– Aerosol – Pasta
– Patch/emplastrum
• Solid
– Pulvis
Transdermal drug delivery

• Scopolamin
• Nitrogliserin
• Estradiol
• Clonidine
• Fentanyl
• Nicotine
 Otic (Auricularis)
Drugs that are instilled in the
external ear canal by direct local
application are used almost
exclusively for their local effects
• The ideal methode of drug administration into the
ear canal is direct local application. Because the
surface of the canal are covered with a thin layer
of cerumen, this region is able to tolerate most
drugs
• Chemical substance that may be palced in the ear
provided the tympanic membrane is intact
Dosage form Drugs commonly used

Should be manufactured • Antibiotic

in a non aquos, water- • Antiinflamatiory
miscible vehicle such as • Anesthetic
glycerol or propylene • Relief pain
glycol
• Anti fungi
• solusio
• suspensi
• unguentum
 Ophtalmica

Drugs are most commonly applied directly to the

eye in the form of eye drops or an ointment
The treatment
mechanism

Internal(anterior chamber)
External(tear chamber)

Topikal administration Sistemic administration

Cornea: epitelim
(lipofilik), stroma
Tear turnover
(hidrofilik),
Drainage endotelium (lipofilik)
Metabolism
Drug dilution
Turnover of aqueous
Metabolism humor
Protein binding Protein binding

Schematic representation of the sites and factors that influence the effectiveness of a drug in the eye
Mekanisme absorbsi ocular

• Absorbsi non kornea :

– Penetrasi melalui sklera dan konjungtiva kedalam jaringan
intraokular
– Tidak produktif krn obat yg penetrasi diabsorbsi oleh
sirkulasi sistemik
• Absorbsi kornea
– Epitelium okular : hanya untuk partikel ionic yang kecil dan
molekul lipofilik
– Transport Transseluler : transport diantara epitel kornea
dan stroma
Eye drops

most ocular medications are

delivered topically - maximizes
anterior segment concentrations
and minimizes systemic toxicity
drug gradient from tear reservoir to
corneal and conjunctival epithelium
forces passive absorption
Eye drops

Factors affecting absorption:

drug concentration (limited by tonicity)
and solubility (aqueous solution v’s
suspension)
viscosity (increased residence time)
Eye drops

lipid solubility: lipid rich epithelial cell

membrane v’s water rich stroma
pH and ionic charge - most eye drops
are weak bases existing in both
charged and uncharged forms
enhancing absorption
Eye drops

Surfactants - preservatives used are

surface-active agents that alter cell
membranes in the cornea as well as
bacteria, increasing drug permeability
and preventing bacterial contamination
Eye drops

Reflex tearing: ocular irritation and

secondary tearing wash out of the drug
reservoir in the tears and reduce
contact time with cornea. This occurs
when drops are not isotonic, have non-
physiological pH or contain irritants
Eye drops
Tissue binding: proteins in the tears
and on the ocular surface may bind
drug making the drug unavailable or
creating a slow release reservoir.
This may affect peak effect and
duration of action as well as delayed
local toxicity eg. ongoing toxic
retinal effects of hydroxychloroquine
even after discontinuation
Eye ointments

increases contact time of drug with

ocular surface
mixture of petrolatum and mineral oil
water-soluble drugs are insolvent in
the ointment and are present as
microcrystals. The surface
microcrystals dissolve in the tears,
the rest are trapped until the
ointment melts
Eye ointments

only drugs with high lipid solubility

and some water solubility will get
into both tears and corneal
epithelium eg. chloramphenicol and
tetracycline both achieve higher
aqueous levels as ointment rather
than drops
Peri-ocular injections
subconjunctival, subTenon’s and
retrobulbar
allow drugs to bypass the
conjunctival/corneal epithelial barrier
and reach therapeutic levels in the
posterior segment
eg anaesthetic agents, steroids,
botulinum toxin
Intraocular injections

allow instant drug delivery at

therapeutic concentrations to target
site
intracameral eg. antibiotics,
viscoelastics, miochol
intravitreal eg. triamcinolone,
avastin
Systemic

drug getting into eye from systemic

circulation limited by tight junctions
in vascular endothelium of retinal
vessels, and non-pigmented
epithelium of ciliary body
drugs with higher lipid solubility
pass through blood-ocular barrier
more readily
Systemic

extent of drug bound to plasma

proteins also effects access of drug
into eye - only unbound form can
pass blood-ocular barrier
bolus administration exceeds the
capacity of a drug to bind to plasma
proteins and so leads to higher
intraocular drug levels than with slow
IV drip
Inhalation (pulmonary drug
delivery)
 Drug administration through
respiratory tract
 Useful for treatment of
pulmonary conditions and for
delivery of drugs to distant target
organs via the circulatory system
videoplayback_5.FLV
 Mechanism
 The respiratory tract can be
considered as comprising
conducting (central) regions
(trachea, bronchi,
bronchioles, terminal and
respiratory bronchioles) and
respiratory (peripheral)
regions (respiratory
bronchioles and alveolar
regions.

 The lungs provide an

excellent surface for
absorption when the drug is
delivered in gaseous, aerosol
mist or ultrafine solid particle
form
The advantages of Transmucosal route

• Generally efficient because the

stratum corneum epidermis, the
major barrier to absorption across the
skin, is absent
• Rich blood suplly (rapid drug
transport to systemic circulation)
avoiding degradation by first-pass
hepatic metabolism
 The amount of the drug

Absoption Distribution
 Drug concentration  Formulation
 Vehicle of drug delivery  Dilution
 Mucosal contact time
 Particle size
 Venous drainage of the
mucosal tissues  Lipid solubility
 Degree of the drug’s  Method of
ionization and the pH of the administration
absorption site  Site of administration
 Size of the drug molecule
 Relative lipid solubility
Consider Potential Problems or concern

• Drug metabolism in the respiratory

tract and reduction of systemic effect
• Possible conversion to carcinogen
• Protein binding
• Mucociliary transport causing
increased or decreased drug
residence time
• Local toxic effects of the drug ( edema,
cell injury, altered tissue defenses
Doasge form

• Aerosol
• Deposition the drugs
depend on:
– Physco-chemical
characteristicss
– Formulation
– Clinical status of patient
– Respiratory pattern dan
pola pernapasan
Matered dose inhalers
Dry powders inhaler
Unit dose
Multi dose
Nebulizer
Nasal

Administration into the nasal

cavity is used primarily to
produce local and systemic
effects
Nasal mucosal surface
provides a site for rapid and
relatively painless
mechanism
Advantages Disadvantages
• Convenient • Specific formulation (high
• Useful area for absorption cost)
• Good systemic blood
suplly
• Avoid first pass
metabolism effects
 Rectal

Drug administration through mucosal rectum for local

and systemic effects
Mechanism

• Lower and middle

haemorrhoidal veins
for general circulation
• Upper to pertal veins
Absorption : Release mechanism
 Formulation  Melting
 Liquid volume  Spreading
 Drug concentration  Sedimentation
 Wetting
 Size of catethter
 Dissolution
 Fecal deposition
 Rectum retention
 Veins drainage
Dosage form

• solid • liquid
– Tablet/suppositoria – Solution
– Enema

• Semisolid
– Unguentum
– cream
• Local • Systemic
 Analgesik  bronchodilator
 Antipriritust  Analgesik/NSAID
 Astringen  Tranquilizers
 Antibiotic/antiseptic
 Local anaethesi
 Vasoconstrictor
 Antiinflamation
 Protectif agent
 Laxant
 Pervaginam
Drug administration through vaginal for local and
systemic effects
Advantages Disadvantages

• Reduce the dose • Local irritation

of drug
• Convinient
• Reduce the
adverse effects
• Avoid first pass
effect metabolism
• Local • Systemic
– Antibiotic (trichomonas) – Hormon estrogen and
– Anti fungi (candidiasis) progesteron
– Induces Uterus
contractility
Dosage form
• Tablets
• capsule
• Pessaries
• Solution
• Spray
• Foam
• cream
• Ointments
Time of drug administration

Learning Objective
• Optimum of therapeutic effect
• Reduce side effect
The factors should be considered
in time of drug administration

• Interval
• Duration
• Time use of the drug
Interval : half life & MIC
Duration
Time use of drug

• Mane, vespere, an
• ac, dc, pc
• Post defecatio
• ue
• Uc
• prn
R/ Cap Asam mefenamat 500 mg No XII
∫ 3 dd cap I pc R/Tab Loratadine 10 mg No X
∫ 1 dd tab I an
љ
љ
R/ Tab Enzympleks No XX
∫ 3 dd tab I dc

љ
Selamat
belajar

References

1. Barry B,2007. Transdermal drug delivery in Pharmaceutical.ed 2nd.editor Aulton M.

Elsevier science
2. Berlin Cheston,1997. Alternative routes of drug administration. Pediatrics vol.100 no1.
3. Joenoes naninzar Zaman, 1998. Ars Prescrebendi; resep yang rasional.Surabaya.AUP
4. Taylor K,2007.Pulmonary drug delivery in Pharmaceutical.ed 3 th. Editor Aulton M.
Elsevier science
5. Taylor P,2007. Nasal drug delivery in Pharmaceutical.ed 3 th.editor Aulton M. Elsevier
science
6. Tukker J,2007. Rectal and vaginal drug delivery in Pharmaceutical.ed 3 th.editor Aulton
M. Elsevier science
7. Robinson D et al,1989. Drug delivery and administration in Pharmacotherapy. Editor
DiPiro J. Elsevier
8. York P, 2007. Drug dosage form in Pharmaceutical.ed 3 th.editor Aulton M. Elsevier
science
9. Walters K,Roberts M. The structure and function of skin.