MODULE 4.

Module Introduction

PHARMACEUTICS
- Drug substances are seldom administered alone; rather they are given as part of a
formulation in combination with one or more nonmedicinal agents that serve varied and
specialized pharmaceutical functions.
- Selective use of these nonmedicinal agents, referred to as pharmaceutical
ingredients or excipients, produces dosage forms of various types.
- The pharmaceutical ingredients solubilize, suspend, thicken, dilute, emulsify, stabilize,
preserve, color, flavor, and fashion medicinal agents into efficacious and appealing
dosage forms.
- Each type of dosage form is unique in its physical and pharmaceutical characteristics.
- These varied preparations provide the manufacturing and compounding pharmacist
with the challenges of formulation and the physician with the choice of drug and
delivery system to prescribe.
- The general area of study concerned with the formulation, manufacture, stability, and
effectiveness of pharmaceutical dosage forms is termed pharmaceutics.

MODULE 4.1. Routes of Administration (1/4)

Drugs may be administered using a variety of dosage forms and routes of
administration. One of the fundamental considerations in dosage form design is whether
the drug is intended for local or systemic effects. Local effects are achieved by direct
application of the drug to the desired site of action, such as the eye, nose, or
skin. Systemic effects result from the entrance of the drug into the circulatory system
and transport to the cellular site of its action. For systemic effects, a drug may be placed
directly in the bloodstream via intravenous injection or absorbed into the venous
circulation following oral or other route of administration.
The route of administration is determined by the properties of the drug (for example,
water or lipid solubility, ionization) and by the therapeutic objectives (for example, the
desirability of a rapid onset, the need for long-term treatment, or restriction of delivery to
a local site).
The table and illustration below present the brief summary of routes, modes, or methods
of drug administration with their corresponding sites. These routes will be tackled in
details in the following discussion.
 ROUTES OF DRUG
ADMINISTRATION

TERM SITE

Oral Mouth
Peroral (per osa) Gastrointestinal tract via mouth
Sublingual Under the tongue
Parenteral Other than the
gastrointestinal tract (by
injection)
Intravenous Vein
Intra-arterial Artery
Intracardiac Heart
Intraspinal or Spine
intrathecal
Intraosseous Bone
Intra-articular Joint
Intrasynovial Joint fluid area
Intracutaneous, Skin
intradermal
Subcutaneous Beneath the skin
Intramuscular Muscle
Epicutaneous Skin surface
(topical)
Transdermal Skin surface
Conjunctival Conjunctiva
Intraocular Eye
Intranasal Nose

Aural Ear
Intrarespiratory Lung
Rectal Rectum
Vaginal Vagina
 MODULE 4.1. Routes of Administration (2/4)
Enteral Routes of Drug Administration

Enteral administration (administering a drug by mouth) is the safest and most common,
convenient, and economical method of drug administration. The drug may be swallowed,
allowing oral delivery, or it may be placed under the tongue (sublingual), or between the gums
and cheek (buccal), facilitating direct absorption into the bloodstream.
1. PERORAL (by mouth) ROUTE

Drugs are most frequently taken by peroral administration. Although a few drugs taken orally
are intended to be dissolved in the mouth, nearly all drugs taken orally are swallowed. Of these,
most are taken for the systemic drug effects that result after absorption from the various
surfaces along the gastrointestinal tract. A few drugs, such as antacids, are swallowed for their
local action in the gastrointestinal tract.
Compared with alternative routes, the peroral route is considered the most natural,
uncomplicated, convenient, and safe means of administering drugs. Disadvantages of the oral
route include slow drug response (compared with parenterally administered drugs); chance of
irregular absorption of drugs, depending upon such factors as constitutional makeup and the
amount or type of food in the gastrointestinal tract; and the destruction of certain drugs by the
acid reaction of the stomach or by gastrointestinal enzymes.
What is first-pass hepatic metabolism?  When a drug is absorbed from the GI tract, it enters the
portal circulation before entering the systemic circulation. If the drug is rapidly metabolized in
the liver or gut wall during this initial passage, the amount of unchanged drug entering the
systemic circulation is decreased. This is referred to as first-pass effect.
2. SUBLINGUAL/BUCCAL ROUTE
Sublingual Route
Placement under the tongue allows a drug to diffuse into the capillary network and enter the
systemic circulation directly. Sublingual administration has several advantages, including ease
of administration, rapid absorption, bypass of the harsh gastrointestinal (GI) environment, and
avoidance of first-pass metabolism.

Buccal Route
The buccal route (between the cheek and gum) is similar to the sublingual route but with
slower and sustained rate of absorption than sublingual.
3. RECTAL ROUTE
Some drugs are administered rectally for their local effects and others for their systemic effects.
Drugs given rectally may be administered as solutions, suppositories, or ointments. Rectal
administration for systemic action may be preferred for drugs destroyed or inactivated by the
environments of the stomach and intestines. The administration of drugs by the rectal route
may also be indicated when the peroral route is precluded because of vomiting or when the
patient is unconscious or incapable of swallowing drugs safely without choking.
Approximately 50% of a dose of drug absorbed from rectal administration is likely to bypass the
liver, an important factor when considering orally administered drugs that are rapidly
destroyed in the liver by the first-pass effect. On the negative side, compared with peroral
administration, rectal administration of drugs is inconvenient and offensive to some patients,
and the absorption of drugs from the rectum is frequently irregular and difficult to predict.

MODULE 4.1. Routes of Administration (3/4)

Parenteral Routes of Drug Administration
The parenteral route introduces drugs directly into the systemic circulation. Parenteral
administration is used for drugs that are poorly absorbed from the GI tract (for example,
heparin) or unstable in the GI tract (for example, insulin). Parenteral administration is also used
if a patient is unable to take oral medications (unconscious patients) and in circumstances that
require a rapid onset of action. In addition, parenteral routes have the highest bioavailability
and are not subject to first-pass metabolism or the harsh GI environment. Parenteral
administration provides the most control over the actual dose of drug delivered to the body.
However, these routes of administration are irreversible and may cause pain, fear, local tissue
damage, and infections. The three major parenteral routes are intravascular (intravenous or
intra-arterial), intramuscular, and subcutaneous
 
MAIN TYPES OF PARENTERAL ADMINISTRATION
1. Intravenous (IV) administration

 IV injection is the most common parenteral route. IV delivery permits a rapid effect and
a maximum degree of control over the amount of drug delivered. When injected as a IV
bolus, the full amount of drug is delivered to the systemic circulation almost
immediately. If administered as an IV infusion, the drug is infused over a longer period
of time, resulting in lower peak plasma concentrations and an increased duration of
circulating drug levels.
2. Intramuscular (IM) administration

 Intramuscular injections are performed deep into the skeletal muscles, generally the
gluteal or lumbar muscles. The selected site is where the danger of hitting a nerve or
blood vessel is minimal.

 Drugs administered IM can be in aqueous solutions, which are absorbed rapidly, or in

specialized depot preparations, which are absorbed slowly.
3. Subcutaneous (SC) administration

 The subcutaneous (hypodermic) administration of drugs entails injection through the

skin into the loose subcutaneous tissue. Subcutaneous injections are generally given in
the forearm, upper arm, thigh, or buttocks. If the patient is to receive frequent
injections, it is best to alternate injection sites to reduce tissue irritation.

 SC injection provides absorption via simple diffusion and is slower than the IV route. SC
injection minimizes the risks of hemolysis or thrombosis associated with IV injection and
may provide constant, slow, and sustained effects.
OTHER TYPES OF PARENTERAL ADMINISTRATION
1. Intradermal (ID) injection

 Intradermal injections are administered into the corium of the skin, usually in volumes
of about 0.1 mL. Common sites for the injection are the arm and the back. The injections
are frequently performed as diagnostic measures, as in tuberculin and allergy testing.
2. Intra-arterial injection

 Used in chemotherapy to target drug to organ

3. Intrathecal Injection

 Drug is directly injected into cerebrospinal fluid (CSF) for uptake into brain
4. Intraperitoneal injection

 Used commonly in laboratory animals

 MODULE 4.1. Routes of Administration (4/4)
Topical Routes of Drug Administration

EPICUTANEOUS ROUTES
1. Topical Application
Topical application is used when a local effect of the drug is desired. For example, clotrimazole
is a cream applied directly to the skin for the treatment of fungal infections.

2. Transdermal (Percutaneous) Route

This route of administration achieves systemic effects by application of drugs to the skin,
usually via a transdermal patch. The rate of absorption can vary markedly, depending on the
physical characteristics of the skin at the site of application, as well as the lipid solubility of the
drug. This route is most often used for the sustained delivery of drugs, such as the antianginal
drug nitroglycerin, the antiemetic scopolamine, and nicotine transdermal patches, which are
used to facilitate smoking cessation.

 
 INHALATIONAL ROUTES
1. Nasal Inhalation

This route involves administration of drugs directly into the nose. Examples of agents include
nasal decongestants.

2. Oral Inhalation

Oral inhalation routes provide rapid delivery of a drug across the large surface area of the
mucous membranes of the respiratory tract and pulmonary epithelium. Drug effects are almost
as rapid as those with IV bolus. This route is effective and convenient for patients with
respiratory disorders (such as asthma or chronic obstructive pulmonary disease), because the
drug is delivered directly to the site of action, thereby minimizing systemic side effects.

 
 OTHER TOPICAL ROUTES
1. Ocular Routes

Ophthalmic solutions and suspensions are sterile aqueous preparations with other ingredients
essential to the safety and comfort of the patient. Ophthalmic ointments must be sterile and
free of grit. Ocular routes of drug administration  will be further elucidated in details in Ocular
Pharmacology.

2. Otic Routes

Ear preparations are usually viscid so that they have prolonged contact with the affected area.
They may be employed simply to soften ear wax, to relieve an earache, or to combat an ear
infection.

3. Intraurethral and Intravaginal Routes

Intravaginal administration is a route of administration where the

substances such as vaginal cream, vaginal tablets, suppositories are applied
inside the vagina.
Intraurethral administration is a route of administration where the
substances such as urethral cream, urethral tablets, suppositories are
applied inside the urethra.
 MODULE 4.2. Drug Dosage Form Designs (1/5)

The proper design and formulation of a dosage form require consideration of the physical,
chemical, and biologic characteristics of all of the drug substances and pharmaceutical
ingredients to be used in fabricating the product. The drug and pharmaceutical materials must
be compatible with one another to produce a drug product that is stable, efficacious, attractive,
easy to administer, and safe. The product should be manufactured with appropriate measures
of quality control and packaged in containers that keep the product stable. The product should
be labeled to promote correct use and be stored under conditions that contribute to maximum
shelf life.
Why a need for pharmaceutical dosage forms?

Besides providing the mechanism for the safe and convenient delivery of accurate dosage,
dosage forms are needed for additional reasons:

 To protect the drug substance from the destructive influences of atmospheric oxygen or
humidity (coated tablets, sealed ampuls)

 To protect the drug substance from the destructive influence of gastric acid after oral
administration (enteric-coated tablets)

 To conceal the bitter, salty, or offensive taste or odor of a drug substance (capsules,
coated tablets, flavored syrups)

 To provide liquid preparations of drug substances, either as dispersions (suspensions)or

as  clear preparations (solutions)

 To provide rate-controlled drug action (various controlled-release tablets, capsules, and

suspensions)To provide optimal drug action from topical administration sites (ointments,
creams, transdermal patches, and ophthalmic, ear, and nasal preparations)
 To provide for insertion of a drug into one of the body’s orifices (rectal or vaginal
suppositories)

 To provide for placement of drugs directly in the bloodstream or body tissues

(injections)

 To provide for optimal drug action through inhalation therapy (inhalants and inhalation
aerosols)

 
The table below shows different routes of administration and their corresponding primary
dosage forms. These dosage forms will be further elucidated with the following discussions.
ROUTE OF ADMINISTRATION
AND DELIVERY SYSTEM OF
PRIMARY DOSAGE FORMS

ORAL Tablets
Capsules
Solutions
Syrups
Elixirs
Suspensions
Magmas
Gels
Powders
SUBLINGUAL Tablets
Troches, lozenges Drops
(solutions)
PARENTERAL Solutions
Suspensions
EPICUTANEOUS, Ointments, gels
TRANSDERMAL Creams
Infusion pumps
Pastes
Plasters
Powders
Aerosols
Lotions
Transdermal patches, disks,
solutions
CONJUNCTIVAL Contact lens inserts Ointments
INTRAOCULAR, Solutions
INTRAAURAL Suspensions
INTRANASAL Solutions
Sprays
Inhalants
Ointments
INTRARESPIRATORY Aerosols
 RECTAL Solutions
Ointments
Suppositories
Gels
VAGINAL Solutions
Ointments
Emulsion foams
Gels
Tablets
Inserts, suppositories, sponge
URETHRAL Solutions, Suppositories

MODULE 4.2. Drug Dosage Form Designs (2/5)

Solid Dosage Forms and Drug Delivery Systems

Powders and Granules

• Oral Powdersgenerally supplied as finely divided powder or
as effervescent granules. The finely divided powders are
intended to be suspended or dissolved in water or mixed with
soft food prior admin istration.

• Effervescent powder for solution in water releases

carbon dioxide which makes for the taste of salty or
bitter medication.

Dentifrices — may be prepared in the form of bulk powder

generally containing soap or detergent, nild abrasive and
anti caries effect.
- designed to be used with toothbrushes to remove
dental stains, to introduce a fresh, pleasant and clean
feeling, and to deliver active agents into tie oral cavity.
 • Douche Powders — soluble powders intended to be dissolved in
water prior to use as antiseptic or cleaning agent for a body cavity.
They are most commonly intended for vaginal use.

Powders and Granules

• Dusting Powder- Locally applied non-toxic preparations that are intended
to have no systemic action. They are applied to various parts of the body as
lubricants, protectives, adsorbents, antiseptics, anti pruritic, astringents
and antiperspirants.

Powders and Granules

• Insufflations — finely divided powders introduced into the body cavities
such as the ears, nose, throat, tooth sockets, and vagina with the use of
insufflator (powder blower).

Capsules
• These are the dosage forms in which unit doses of powder, semisolid, or
liquid drugs are enclosed in a hard or soft, watersoluble container or
shell of gelatin.
 Tablets

• These are solid dosage forms containing drug

substance with or without suitable diluents
and are prepared either by compression or
molding method.
Compressed tablets
• Sugar Coated tablet (SCT) — tablet coated with a
colored or uncolored sugar layer.

• Diclofenac

Compressed tablets
• Film-coated Tablet (FCT) — tablets coated with a thin layer of polymer
capable of forming a skin like film.

Compressed tablets
• Multiple Compressed Tablet (MCT)— a multiple-layer or a tablet
with in a tablet, the inner tablet being the core and the outer
portion being the shell.

Compressed tablets
• Controlled-release Tablet (CRT) is a drug or preparation that is
released into the body in specified amounts over a specified
period of time. The controlledrelease system is designed to release
the drug's active ingredient gradually over the day.
 Compressed tablets

*Enteric-coated Tablet (ECT) — is designed to pass unchanged through

the stomach to the intestines, where it disintegrates, dissolves, and
absorbs.

• Multiple Compressed Tablet

(MCT)— a multiple-layer or a tablet with in a tablet, the inner tablet being the
core and the outer portion being the shell.

Compressed tablets
• Controlled-release Tablet (CRT) is a drug or preparation that is released into the
body in specified amounts over a specified period of time. The controlledrelease
system is designed to release the drug's active ingredient gradually over the day.

Compressed tablets
Gelatin-coated tablet — gelcap, a capsule shaped compressed tablet
that allows the coated product to be about one-frird smaller than a
capsule filled with an equivalent amount of powder.
Effervescent Tablet — contain medicinal substances that dissolve generally when added
to water.

Compressed tablets

• Buccal and Sublingual tablets- are flat, oval tablets

intended to be dissolved in the buccal pouch or beneath
the tongue. Perlingual, Peroral

Compressed tablets
Buccal and Sublingual tablets are flat, oval tablets intended
to be dissolved in the buccal pouch or beneath the tongue. •
Clonidine (Catapres)

Chewable tablets — have a smooth disintegration when chewed and allowed

to dissolve in the mouth.

Compressed tablets
Immediate release tablet are designed to disintegrate and release their
medication with no special rate controlling features such as special coating and
techniques
Lozenges/Troches/ Pastilles
are discoid shaped solid containing the medicinal agent in suitable flavored
base. They are placed in the mouth where they are slowly dissolve.

Lollipops
• Lollipops are lozenges type of oral solid dosage form with a short stick inserted
into it which produces local effect in the mouth

Pills
• small, round, solid dosage form containing medicinal agents and
intended for oral administration.

Pellets
• small, sterile cylinders formed by
compression from medicated masses.
 MODULE 4.2. Drug Dosage Form Designs (3/5)
Semisolid and Transdermal Dosage Forms and Drug Delivery
Systems

Semi solid and transdermal

• Ointments- semi-solid
preparations intended
for external application
to the skin or mucous
membranes, usually
contain medicinal
substance
• Mupirocin

Semi solid and transdermal

• Creams — viscous liquid or semi-solid emulsions of either

oil in water or water in oil type. O/W type includes shaving
creams, hand creams, foundation cream. W/O type creams
include cold creams and emollient creams

Semi solid and transdermal

• Gels -are defined as semisolid systems consisting of dispersion
made up of either small inorganic particles or large organic
molecules enclosing and interpenetrated by a liquid

Semi solid and transdermal

• Transdermal preparations - (often called

transdermal patches) deliver drugs directly
through the skin and into the bloodstream.
 Inserts

—Suppositories and Inserts — are solid dosage form intended for

insertion into body orifices (e.g., rectum, vagina, or urethra).

Liquid Dosage Forms and Drug Delivery Systems

Aqueous solutions

• Enemas — can be retention or

evacuation enemas. Evacuation
enemas are rectal preparations
employed to evacuate the bowel.
Retention enemas, while producing
the same effects, are intended to
remain in the rectum a longer period
of time penetrating and thus
lubricating the feces further.
Aqueous

• Gargles— aqueous solutions used for treating the

nasopharynx by forcing
air from the lungs
through gargle which is
held in the throat.

Aqueous solutions

• Mouthwashes— aqueous solutions

which are most often used for their
deodorant, refreshing, or antiseptic
effect.

Sweet and
other viscid
aqueous
solutions
• Syrups— concentrated
solutions of sugar such as sucrose
 in water or other aqueous liquid. They are used either as flavored
syrup or medicated syrup.

Sweet and other viscid aqueous solutions

• Jellies— class of gel in which the structural coherent matrix

contain a high proportion of liquid,
usually water. They are used as
lubricant for surgical gloves, catheters,
and rectal thermometer.
 • Collodion — liquid preparations containing
pyroxylin in a mixture of ethyl ether and
ethanol. They are applied to the skin by
means of a soft brush or other suitable
applicator and when the ether and ethanol
have evaporated, they leave a film of
pyroxylin on the surface.

Non-aqueous solutions

• Elixirs — clear, pleasantly flavored

sweetened hydro alcoholic liquids
intended for oral use. They are used
as flavors and vehicles.
• Types: Non medicated
Medicated
• Inhal
a tions and
inhalants -
Inhalation are
drugs or
solutions of
drugs
administered by
the nasal or oral
respiratory
route for local
 or systemic effect. Inhalants are a special class of
inhalation which consists of drugs or combinations of
drugs that by virtue of high power pressure can be
carried by air current into the nasal passage where
they extend their effect. Nebulizers are used for the
administration Of inhalation.

Non-aqueous solutions

• Liniments — solutions or mixtures of

various substances in oil, alcoholic
solutions of soap or
emulsion. They are
intended for external
application. They are
applied by being
rubbed on the
affected area.
•
• Spirit
s —

popularly known as essence are alcoholic

hydro alcohol solutions of volatile
substance. They are used medicinally as
inhalation or as favoring agent.
Non-aqueous solutions

• Toothache drops — preparation used

for temporary relief of toothache by
application of cotton saturated with
the product into the tooth cavity.

MODULE 4.2. Drug Dosage Form Designs (4/5)

Disperse Drug Delivery Systems

Disperse systems

• Suspensions-
are
dispersions
of finely
divided
solid
particles of
a drug in a
liquid
medium in
which the drug is not readily soluble.
 Disperse systems

• Emulsion- is a thermodynamically unstable system that consists

of at least two immiscible liquid phases— one of which is
dispersed as globules (dispersed phase) and the other, a liquid
phase (continuous phase)—that are stabilized by the presence
of an emulsifying agent.

Disperse
systems
• Aerosols- are
pressurized
dosage forms
that upon
actuation
emit a fine dispersion of liquid and/or solid
materials containing
one or more active
ingredients in a
gaseous medium

Sterile Drug Dosage Forms

Sterile Dosage Forms

 • Parenteral Preparation —
sterile preparation
intended to be
administered by injection
under or through one or
more layers of skin or
mucous membranes.
They are usually packed
in ampules or vials.

Sterile Dosage Forms

Intravenous admixture- a combination of one or more sterile
products added to an IV fluid for administration.

Sterile Dosage
Forms

Intravenous fluids
— sterile, large volume
solutions intended to be
administered via infusions;
they contain sugar, amino
acids, or electrolytes
Sterile Dosage Forms

• T
ot
al

parenteral nutrition (TPN) — it contains

amino acids, carbohydrates, lipids, and
other nutrients in sufficient quantities. for
Active Immunity

• Vaccines
- a

suspension of attenuated (live) or

 inactivated (killed) microbes or fraction
thereof administered
to induce immunity infectious disease.

LEE and thus prevents

Biologics for Active Immunity

• Toxoids- modified

laa antigen from an

infectious organism used as a vaccines.
• Human Immune sera — contain that specific
antibodies obtained from the blood of
humans
and
produces
as a result
of having
had the specific disease or having immunized
against it with a specific biologic product.

Biologics for Passive Immunity

• Immunoglobulin — a
solution containing
antibodies from the
pooled plasma of not less
than 1,000 normal
individuals

Animal Immune serum

 Lens care
• Hyper immune Serum—a special preparation obtained from
human donor pools selected for
high antibody titer against a
specific disease.

Biologics for Passive Immunity

Animal Immune serum

• Antitoxin- a solution of
antibodies derived from the
serum of animals immunized
with specific toxins (toxoids)
used to achieve passive
immunity or to effect a
treatment.
 Lens care
Animal Immune serum

• Antiviral Serum —a solution of antibodies derived from

the serum of animals immunized vith specific viral
vaccines.

Biologics for Passive

Immunity Animal
Immune serum
• Antivenin — A preparation of
antibodies derived from the serum of
animals immunized with specific
venom used to neutralize the venoms
produced by the specific organism.
 Lens care

MODULE 4.2. Drug Dosage Form Designs (5/5)

Special Solutions and Suspensions

Special Solutions and

Suspension

• Ophthalmic— sterile
preparations to be used
on the eyes
 Lens care
Special Solutions and Suspension

• Solutions- intended for the eye; clear, sterile solution to be

instilled into the eyes by
the use of dropper.

Special Solutions and Suspension

• Suspensions dispersion of
finely divided relatively
insoluble drugs substances
in an aqueous vehicle
containing suitable
suspending and dispersing
agent

Special Solutions and Suspension

• Ointments — intended for the eyes; contain medicinal agents
added to the ointment base either
as solution or as micronized
powder.

products
 Lens care
• Wetting solutionspreparations designed to furnish hydrophilic
coating over the characteristically
hydrophilic surface of hard
contact lens surfaces

Lens care products

Cleaning solutions- Used to remove

surface contaminants, lipids,
proteins and the like.
 Lens care
products
• Disinfecting solutionsisotonic; in an acceptable pH range nonreactive with
lens material and sterile solution which exhibits disinfecting activity.

Lens care products

• Soaking solutions— used to store and hydrate hard lenses and to disinfect
lenses.

products

• Artificial tearssolution intended to

rewet hard lenses.

Nasal preparations
• Inhalation solutions - are drugs or solutions of drugs
administered by the nasal or oral respiratory route.

Otic preparations

• Otic preparations- are usually placed in the

ear canal in small amounts for removal of
excess cerumen or for treatment of ear
infection, inflammation or pain
Lens care