Ch1. intro pharmaceutical

Bule Hora University
College of Health and Medical Sciences
Department Of Pharmacy
INTEGRATED PHYSICAL PHARMACY AND PHARMACEUTICS I
CHAPTER 1
INTRODUCTION TO DOSAGE FORMS AND ROUTES OF DRUG ADMINISTRATION
By: Aliyi Gerina [BSc, B.pharm]
4/5/2022
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Intrroduction to DF and Routes of Drug administration by Aliyi Gerina

Out line
 Introduction to pharmaceutics
 Pharmaceutical dosage forms
 Pharmaceutical excipients
For Solid dosage forms
For liquid dosage forms
For semi solid forms
 Routes of drug administration
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Intrroduction to DF and Routes of Drug administration by Aliyi
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Introduction
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Introduction
 Pharmaceutics can be defined as :
 “ The general area of study concerned with the
formulation , manufacture, stability and effectiveness
of pharmaceutical dosage forms”.
Or:
 “ The science that deals with the dosage form design”
 Pharmaceutics converts a drug (API) into a medicine.
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Areas of Pharmaceutics
 An understanding of the basic physical chemistry
necessary for the effective design of dosage forms
(Physical pharmacy)
 The design and formulation of dosage form (dosage
form design)
 The manufacture of these medicines on a small
(compounding),intermediate (pilot -scale) and large
(pharmaceutical technology, manufacturing) scale.
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Areas of Pharmaceutics,…
 An understanding of relevant body systems and how
drugs arrive there following administration
(Biophamaceutics)
 The avoidance and elimination of microorganisms in
medicines (pharmaceutical microbiology, sterilization),
and
 Product performance testing (dissolution testing, drug
release, stability testing)
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Pharmaceutical dosage forms (PDF)
Definition:
Dosage forms
are the means by which drug molecules are delivered to
sites of action within the body.
are designed to facilitate the administration of drug
substances.
Contains API + inactive pharmaceutical ingredients
(excipients).
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Cont’d,…
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Active Pharmaceutical Ingredient (API)
Is a chemical compound with pharmacological (or
other direct effect) intended for used in diagnosis,
treatment or prevention of diseases.
Inactive Pharmaceutical Ingredient (Excipients)
Excipients are pharmaceutical additives, the inactive
ingredients used to make up a medication.
include colorant, flavors, binders, emollients, fillers,
lubricants, preservatives,...
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Cont’d,…
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Drug
Defined as an agent intended for use in the diagnosis,
mitigation, treatment, cure, or prevention of disease in
humans or in other animals.
Medicine (Drug product)
 A drug delivery system.
 A means of administering drugs to the body in a safe,
efficient, reproducible and convenient manner.
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Why dosage forms are needed?
Direct clinical use of the API, ‘as they are’ is rare due to
the number of good reasons:
 API handling can be difficult or impossible
e.g., low mg and g doses.
 Accurate drug dosing can be difficult or impossible.
 API administration can be impractical,
 unfeasible or not according to the therapeutic aims.
 Some API can benefit from reducing the exposure to
the environmental factors (light, moisture…), or
they need to be chemically stabilized due to the
inherent chemical instability.
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Why dosage forms are needed?,…
 API can be degraded at the site of administration
 e.g., low pH in stomach.
 API may cause local irritations or injury when they
are present at high concentrations at the site of
administration.
 API can have unpleasant organoleptic qualities
 E.g taste, smell – compliance!.
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Classification
They are classified according to:
Oral
Topical
Rectal
Parenteral
Vaginal
Inhaled
Ophthalmic
Otic
 Solid
 Liquid
Semisolid
Gas
Route of administration Physical form
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Classification,…
Physical form Classifications of DFs:
 Solid dosage forms
 Liquid dosage forms
 Semisolid dosage forms
 Gaseous dosage forms
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1. Solid dosage forms
1. Tablet
 is a hard, compressed medication in round, oval or
square shape.
 The API will be compressed along with other
pharmaceutical excipients.
 Used as oral dosage form.
 The excipients include:
 Binders, glidants and lubricants to ensure efficient
tableting.
 Disintegrants to ensure that the tablet breaks up in the
digestive tract.
 Sweeteners and flavors to mask the taste of bad-tasting
active ingredients.
 Colorant to make uncoated tablets visually attractive.
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Solid DF,…
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 Advantages of tablets
1- Compared to liquid dosage forms tablets possess more
chemical and physical stability
2- Packaging in blister packs can also enhance the stability of
tablets
3- They provide an accurately measured dose and low content
variability of the unit dose
4- Low manufacturing cost
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Solid DF,…
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5- Easy to package and ship
6- Simple to identify (Coatings can be colored or stamped to aid
tablet recognition)
7-Manufacturing processes and techniques can provide tablets
special properties
example enteric coatings or sustained release formulations.
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Solid DF,…
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Disadvantages of tablets as a dosage form
1- Poor bioavailability of poorly soluble drugs or poorly
absorbable drugs
2- Some drugs may cause local irritation and harm
gastrointestinal mucosa
3- Some drugs resist compression into tablet
4- Difficulty in swallowing in some patients
e.g. pediatrics and unconscious patients
5- they are not suitable in emergency cases;
 intravenous or intramuscular injections are more effective
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Solid DF,…
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Common types of tablets include:
A. Enteric-coated tablets:
 are a type of tablets intended to release their contents in the small intestine
by passing the acidic stomach.
B. Sustained-release tablets:
 are tablets designed to deliver their contents over time.
 Some drugs are formulated to deliver their contents over 24 hours and
 only need to be taken once a day.
 Sustained-release drugs should be swallowed whole;
 crushing may cause the contents to be released immediately.
C. Film coating and sugar coating tablets:
 are tablets coated to mask their unpleasant taste
 and make them easier to swallow.
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Solid DF,…
D. Sublingual and buccal tablets
 are administered by placing them in the mouth, either
 under the tongue (sublingual) or
 between the gum and the cheek (buccal).
 The medications dissolve rapidly and
 are absorbed through the mucous membranes of the mouth,
 where they enter into the bloodstream.
 Examples of drugs administered by this route:
 e.g. vasodilators.
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Solid DF,…
E. Effervescent tablets
 are uncoated tablets that generally contain
 acid substances (citric and tartaric acids) and
 carbonates or bicarbonates and
 which react rapidly in the presence of water
 by releasing carbon dioxide ↔ disintegration.
 They are intended to be dissolved or dispersed in water
before use.
 providing:
 Very rapid tablet dispersion and dissolution → rapid absorption
 Pleasant tasting carbonated drink.
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Solid DF,…
F. Chewable Tablets
 are chewed within the buccal cavity prior to swallowing.
 Advantage:
 Children and adults who have difficulty in swallowing
conventional tablets.
e.g. vitamin products
 Antacid formulations in which the size of the tablet is
normally large.
 Not used if the drug has issues regarding taste acceptability.
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Solid DF,…
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2- Capsule:
 A capsule is a medication in a gelatin container.
 The gelatin shell dissolves in the stomach, releasing the drug.
 A capsule may contain powders, granules or crushed tablets
with one or more active ingredients and one or more inert
ingredients.
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Solid DF,…
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Advantage:
mask the unpleasant taste of its contents.
easier to swallow but more costly to produce.
Elegance, smooth slippery
Nice presentation of the drug
Portability, convenient
Light weight
Rapid drug release
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Solid DF,…
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The two main types of capsules are:
1- hard-shelled capsules
 consists of two separate components,
 namely the cap and the body.
 normally used for
 dry, powdered ingredients.
Hard gelatin capsule
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Solid DF,…
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2- soft-shelled capsules
 a unit that is formed from one piece and
 where the processes of filling and formation of the outer unit
are carried out in a single operation.
 primarily used for oils and active ingredients that
 are dissolved or suspended in oil.
Soft gelatin capsule
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Solid DF,…
3. Lozenge
 It is a solid preparation consisting of sugar and gum.
 The latter
 giving strength and cohesiveness to the lozenge and
 facilitating slow release of the medicament.
 It is used to medicate the mouth and throat
 for the slow administration of indigestion or cough remedies.
o Dissolved slowly in the mouth
o Lubricate and sooth irritated tissues of the throat.
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Solid DF,…
4. Suppository
a. Rectal suppository
 It is a small solid medicated mass, usually cone-shaped.
 is inserted into the rectum where it melts at body
temperature.
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Solid DF,…
b. Pessaries
 are solid medicated preparations designed for insertion into
the vagina where they melt or dissolve.
 There are three types:
A- Moulded pessaries : they are cone shaped and prepared
in a similar way to moulded suppositories.
B- Compressed pessaries: made in a variety of shapes and
are prepared by compression in a similar manner to oral
tablets.
C- Vaginal capsules: are similar to soft gelatin oral.
 Capsules differing only in size and shape.
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2. Liquid dosage forms
a. Oral solution
 Oral solutions are clear liquid preparations
 for oral use
 containing one or more active ingredients dissolved in a
suitable vehicle.
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Liquid Df,…
b. Syrup
 It is a concentrated aqueous solution of a sugar,
 usually sucrose.
 No need of other
 sweetening agents and
 viscosity-modifying agents
 No addition of preservatives is required
 If high concentration of sucrose.
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Liquid Df,…
c. Elixir
 It is clear hydro-alcoholic solution
 for oral use.
 The vehicle may contain a high proportion of ethanol or
sucrose together with antimicrobial preservatives.
 But if the alcohol content > 12% v/v alcohol
 No need of preservatives:
due to the antimicrobial of alcohol
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Liquid Df,…
d. Oral emulsion:
 Oral emulsions are stabilized oil-in-water dispersions,
 either or both phases of which may contain dissolved solids.
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Liquid Df,…
f. Oral suspension:
 They are liquid preparations
 for oral use
 containing one or more active ingredients suspended in a
suitable vehicle.
 They may show a sediment which is readily dispersed on
shaking
 to give a uniform suspension which remains sufficiently stable to
enable the correct dose to be delivered.
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Liquid Df,…
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g - Linctuses:
 are viscous,
 liquid oral preparations that are
- usually prescribed for the relief of cough.
 They usually contain a high proportion of syrup and glycerol
- which have a demulcent effect on the membranes of the throat.
 The dose volume is small (5ml) and,
- to prolong the demulcent action,
- they should be taken undiluted.
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Liquid Df,…
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h- Gargles:
 They are aqueous solutions
 used in the prevention or treatment of throat infections.
- Usually they are prepared in a concentrated solution with directions
for the patient to dilute with warm water before use.
i- Mouthwashes:
 These are similar to gargles but
 are used for oral hygiene and to treat infections of the mouth.
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3. Semisolid dosage forms
i. Ointments
 are semi-solid, greasy preparations
 for application to the skin, rectum or nasal mucosa.
 Ointments form a transparent unbroken relatively water
impermeable film in the skin.
 Ointments may be used as
 Effective barrier against moisture loss.
 A vehicle to apply suspended or dissolved medicaments
to the skin.
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Semisolid DF,…
ii. Pastes
 are basically ointments into which a high percentage of
insoluble solid has been added.
 Stiff: The extraordinary amount of particulate matter (ZnO).
 Like ointments, paste forms an unbroken relatively water
impermeable opaque film.
therefore can be used as an effective sun block
accordingly.
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Semisolid DF,…
iii. Creams
 Creams are semi-solid emulsions, that is mixtures of oil and
water.
 Creams are emulsions for external use
 as protective or emollients to soften and smooth.
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Semisolid DF,…
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 They are divided into two types:
A- Oil-in-water (O/W) creams:
 small droplets of oil dispersed in a continuous aqueous
phase.
 O/W are
 more comfortable and cosmetically acceptable
 as they are less greasy more easily washed off
using water.
include hand cream, shaving cream and
foundation cream.
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Oil- in-water

Semisolid DF,…
B- Water-in-oil (W/O) creams:
 Small droplets of water dispersed in a continuous oily
phase.
 Advantage:
 Release drug readily
 More moisturizing
 provide an oily barrier which reduces water loss from the
outermost layer of the skin.
 Disadv:
 More difficult to handle.
 include cold cream and emollient cream.
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Water-in-oil

Semisolid DF,…
iv. Gels (Jellies)
 Pharmaceutical gels or jellies are SDF
 composed of a liquid phase within a network structure of a
solid gelling agent (consisting of natural or synthetic gum
or aluminium hydroxide).
 They are used for
 medication,
 lubrication and
 some miscellaneous applications like carrier for spermicidal
agents to be used intra vaginally.
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4. Gaseous dosage forms
Pressurized dispensers (aerosol sprays)
 Several different types of pharmaceutical product may be
packaged in pressurized dispensers, known as aerosols.
 Sprays produce droplets of 100 um diameter or greater.
 May be used as
 surface disinfectants,
 wound or burn dressing,
 relieve irritation of bites.
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Gaseous DF,…
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Inhalers
 are solutions, suspensions or emulsion of drugs in a mixture of
inert propellants held under pressure in an aerosol dispenser.
 Release of a dose of the medicament in the form of droplets
from the container.
 The patient then inhales the released drug through a
mouthpiece.
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Gaseous DF,…
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 In some types, the valve is actuated by finger pressure,
 In other types the valve is actuated by the patient breathing in
through the mouthpiece.
 It is commonly used to treat asthma and other respiratory
problems.
- Because they are cheaper, more portable and carry less risk
of side effects.
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Pharmaceutical
Excipients
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Excipients
Definition:
 Excipients are pharmaceutical additives,
 the inactive ingredients used to make up a medication.
 They include colorant, flavors, binders, emollients,
fillers, lubricants, preservatives, and many more
classifications.
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Excipients, cont’d
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 Pharmaceutical additives must:
 be safe in the amount used in the drug
 not affect the bioavailability and performance of the
drug
 be manufactured in accordance with good standards
- some people may be allergic to some excipients
- e.g., many people are lactose-intolerant.

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Roles of excepients in pharmaceuticals
 Excipients help a drug to disintegrate into particles small
enough
 to reach the bloodstream more quickly.
 protect the stability of the product
 so it will be at maximum effectiveness at time of use.
 Excipients may prevent a drug from dissolving too early,
 protecting against stomach upset.

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 Drug products contain both
 drug substance (commonly referred to API and excipients.
 The resultant biological, physical properties of the drug
product are directly affected by the excipients chosen, their
concentration:
 consistency of drug release and bioavailability,
 stability including protection from degradation,
 ease of administration.

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 Excipients are sub-divided into various functional
classifications, depending on the role that they are
intended to play in the resultant formulation.
 Certain excipients can have different functional roles in
different formulation types,
e.g. lactose; widely used as:
 a diluent, filler or bulking agent in tablets and capsules
 a carrier for dry powder inhalation products.

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 Excipients commonly used
 Excipients used in solid dosage forms
 Diluents (fillers, bulking agents), Disintegrants, Binders,
Lubricants, Glidants, antiadherants.
 Excipients used in liqiud and semisolid dosage forms
 Solvents/co-solvents , Buffering agents, Preservatives,
Anti-oxidants, Wetting agents, Anti-foaming agents,
Thickening agents, Sweetening agents, Flavouring
agents, Humectants.

Excipients for solid dosage
forms
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Diluents
 e.g. lactose, microcrystalline cellulose, Calcium
phosphates, co processed duilents.
 To make a tablet weight practical for the patient:
 To facilitate tablet handling during manufacture and
 to achieve targeted content uniformity.
 minimum tablet weight is typically ~50mg
 actual API doses can be as low as ~20µg,
 Many potent drugs have low dose (e.g. diazepam, clonidine
hydrochloride) in such cases
 ` diluents provide the required bulk of the tablet.

Diluents,…
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 Compression aid
• Deforms and/or fragments readily to facilitate robust bonding
in tablet compacts
e.g. microcrystalline cellulose.
 Good bulk powder flow
 Good flow of bulk powders
 is very important in designing a robust commercial tablet
product.
 Lactose can exhibit poor flow characteristics,
 so is often combined with microcrystalline cellulose, or
 is used as a better-flowing spray-dried version,
 particularly with direct compression formulations.

Binders
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 Binders act as an adhesive to ‘bind together’ powders, granules
and tablets to result in the necessary mechanical strength:
 As a powder with other excipients in dry granulation or as an
extra-granular excipient in a wet granulation formulation.
 As a powder /liquid with other excipients in wet granulation.
 Most commonly, the binder is added already dissolved in the
granulating fluid
 to enable more rapid and, usually, more effective granulation.
Examples:
 Dry binders: Microcrystalline cellulose, cross-linked PVP
 Solution binders: Hydroxy Propyl Methyl Cellulose (HPMC),
polyvinylpyrrolidone (PVP).

Disentegrants
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 As an aid to de-aggregation of compacted tablets.
 Generally, disintegration is viewed as the first stage in the dissolution
process.
Mode of action:
 ↑ the porosity and wettability of the compressed tablet matrix
 Water uptake rupturing the intra-particle cohesive forces that hold the
tablet together → disintegration
 Operate by swelling in the presence of aqueous fluids
Water uptake → swelling →physical rupture →widened the channels for
penetration of water → disintegration
 E.g Starch, MCC, sodium starch glycolate , croscarmellose sodium, crospovidone,
pregelatinised starch.

Lubricants
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 Lubricants prevent adherence of granule/powder to punch
die/faces and
 promote smooth ejection from the die after compaction
 These are used to reduce friction between powders and metal
surfaces during tablet manufacture.
• Magnesium stearate is by far the most extensively used tableting
lubricant.
• Stearic acid, sodium stearyl fumarate etc.

Glidants
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Most commonly; colloidal silicon dioxide , talc)
 Good bulk powder flowability is especially important during high
speed processing
 Glidants improve flow by adhering to particles and
 so reducing inter-particulate friction.
 Most common in dry powder formulations,
e.g. direct compression tablets
 Can also be added to granules
 to improve flow prior to compression.

Organoleptic excipients
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Sweetening agents/flavoring agents
 Sweetening and flavoring agents are employed to
control the taste and hence the acceptability of
tablets
 More important
 If the conventional tablet contains a bitter drug
 If the tablet is a chewable tablet
Colorants
 Colored tablets are generally formulated either
 to improve the appearance or
 to identify the finished product uniquely

Film formers (polymers)
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 High compatibility with other coating solution additives
 Nontoxic with no pharmacological activity
 High resistance to cracking
 should not give bridging or filling of the debossed tablet
 Compatible to printing procedure
 Hydroxy Propyl Methyl Cellulose (HPMC)
 Ethyl Cellulose (EC)
 Sodium carboxy methyl cellulose
 hydroxy Propyl Cellulose (HPC)
 Povidone
 Polyethylene glycols (PEG)

Plasticizers
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 Affords flexibility and elasticity to the coat and
 thus provide durability.
 Combination of plasticizer may be used
 Recommended levels of plasticizers range from 1-50 % by
weight of the film former.
 Commonly used plasticizers are
 castor oil, PG, glycerin, lower molecular weight PEG,
surfactants, etc.
 For aqueous coating PEG and PG are more used while
 Castor oil and spans are primarily used for organic-solvent based
coating solution.

Opaquant-Extenders
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 These are very fine inorganic powder
 used to provide more pastel colors and increase film
coverage.
 provide white coat or mask colour of the tablet core.
 Colourants are very expensive and higher concentration needed
 In presence of these inorganic materials,
 amount of colourants required decreases.
 Most commonly used materials :
 titanium dioxide, talc & aluminum silicates, magnesium
carbonates, magnesium oxide & aluminum hydroxides

Enteric coating polymers
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Enteric coating polymers Properties
Resistance to gastric fluids
Susceptible/permeable to intestinal fluid
Compatibility with most coating components and the drug
Formation of continuous film
Nontoxic, cheap and ease of application
Ability to be readily printed

Enteric coating polymers,…
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Polymers used for enteric coating are:
i. Cellulose acetate phthalate
ii. Acrylate polymers
iii. Hydroxy propyl methyl cellulose phthalate
iv. Polyvinyl acetate phthalate

EXPIENTS USED IN
LIQUID
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In Liquid, the possible types of excipients include:
 Solvents/co-solvents e.g. Aqueous Vehicle, PG, Glycerol
 Buffering agents, e.g. Citrate, Gluconates, Lactates
 Preservatives, e.g. Na Benzoate, Parabens (Me, Pr and Bu)
 Anti-oxidants, e.g. BHA, BHT, Ascorbic acid
 Wetting agents, e.g. Polysorbates, Sorbitan esters
 Anti-foaming agents, e.g. Simethicone
 Thickening agents, e.g. Methylcellulose or Hydroxyethylcellulose
 Sweetening agents, e.g. Sorbitol, Saccharin,Aspartame,Acesulfame
 Flavouring agents, e.g. Peppermint, Lemon oils, Butter scotch, etc.
 Humectants, e.g. PG, Glycerol, Sorbitol

Solvents/vehicles
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 A medium in which ingredients of a dosage form are
dissolved or dispersed.
 Examples of solvents are
 water, alcohol, isopropyl alcohol, glycerol , PG, acetone,…
 Water is the solvent most widely used as a vehicle due to:
• Lack of toxicity, non irritant,
• physiological compatibility,
• Inexpensive and readily available
• good solubilising power

Co-solvents
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Co-solvents are employed
 to increase the solubility of the therapeutic agent within the
formulation.
 Water-miscible co-solvents are used to:
• Enhance solubility, taste, anti-microbial effectiveness
or stability.
• Eg: ethanol, PG, glycerol, low mwt PEGs
 Water-immiscible co-solvents,
e.g. Emulsions / microemulsions using coconut oils.

Alcohol
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Ethanol
 Is flammable and volatile organic solvent that can
solublize most substances.
 Used for both internal and external preparations.
 Has a preservative effect at 20% and more.
 Since it is volatile it rapidly evaporates from the skin and
 thus produce a cooling sensation thus relieve pain.
Propylene glycol,PG
 Viscous, sweet liquid similar to glycerol
 Similar application to glycerol,
 Can serve as a preservative.

Alcohol,…
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Glycerol
 Colorless, viscous, sweet liquid used in both internal and external
preparations usually in combinations.
 Has demulcent effect, e.g., in cough preparations such as
linctuses.
 As a sweetening agent and Moisturizes the skin.
Poly(ethylene glycol) (PEG)
 a polymer composed of repeating units of the monomer ethylene
oxide.
 The physical state of the polymer is dependent on the number of
repeat units (n) and hence on the molecular weight.
 Lower-molecular-weight grades (PEG 200, PEG 400) are
preferred as co-solvents in pharmaceutical solutions.

Preservatives
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 Liquid and semisolid pharmaceutical preparations
 must be preserved against microbial contamination.
 Ideally, preservatives should exhibit the following
properties:
 Possess a broad spectrum of antimicrobial activity
 Be chemically and physically stable over the shelf-life of
the product
 Have low toxicity

Preservatives,…
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 Pharmaceuticals such as
 elixirs, spirits, and tinctures are self sterilizing and
 do not require additional preservation.
E. g. Alcohol, Phenol, Cresol, Benzoic acid / sodium benzoate,
Phenylmercuric nitrate / acetate, Chlorobutanol, Benzalkonium
chloride, Methylparaben / propylparaben, and Others.

Anti-Oxidants
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 Included to enhance the stability of therapeutic agents
 that are susceptible to chemical degradation by oxidation.
 Used to control oxidation of API, Preservative, vehicle(oils or
fats), Colorants.
 Light exposure and metal ion impurities can accelerate oxidative
degradation and hence depletion of API.
Examples:
 Sodium sulphite, sodium metabisulphite, sodium formaldehyde,
ascorbic acid, Butylated hydroxytoluene (BHT), Butylated
hydroxyanisole (BHA).

Wetting Agents
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 To aid ‘wetting’ and dispersion of a hydrophobic API,
preservative or antioxidant.
 Not all are suitable for oral administration
Examples include:
 Surface active agents, e.g.
Oral: polysorbates (Tweens), sorbitan esters (Spans)
Parenteral: polysorbates, poloxamers, lecithin
External: sodium lauryl sulphate
 Hydrophilic colloids e.g. bentonite, tragacanth,
alginates, cellulose derivatives..

Anti-Foaming Agents
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 The formation of foams during manufacturing processes or when
reconstituting liquid DFs can be undesirable and disruptive.
 Anti-foaming agents are effective at discouraging the formation
of stable foams
 by lowering surface tension and cohesive binding of the liquid phase.
 Simethicone (polydimethylsiloxane-silicon dioxide).

Suspending agents
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 Suspension stabilizers: Prevent settling/sedimentation.
 They usually modify viscosity and are often thixotropic
(where viscosity is dependent on applied shear and exhibits
‘shear thinning’).
Easily poured when shaken
Must permit accurate dosing with chosen method (e.g.
graduated syringe,spoon)
Quickly reforms ‘gel-like’ structure.
Can be either
• water-soluble, e.g. methylcellulose or hydroxyethylcellulose
Or
• water-insoluble, e.g. microcrystalline cellulose

Humectants
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 Their function is to retard evaporation of aqueous vehicle
of dosage form:
 To prevent drying of the product after application to the skin.
 To prevent drying of product from the container after first
opening.
 To prevent cap-locking caused by condensation onto neck of
container-closure of a container after first opening
Examples include:
 Glycerol, propylene glycol(PG), PEG

Surfactants/Surface Active Agents
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 Compounds that have two groups present in the
molecule.
 When added to liquid,
 lower interfacial tension between two phases thus makes
them miscible.
 make two immiscible liquids miscible with each other
and to dissolve the drugs, which are normally in soluble
in aqueous vehicles.
 used as emulsifying agents, detergents, solublizing
agent, flocculating and deflocculating agents.

Emulsifying agents
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 Emulsifying agents are substances which stabilize an
emulsion, frequently surfactants.
 Emulsifying agents help the production of a stable
dispersion
 by reducing interfacial tension and
 then maintaining the separation of the droplets by forming
a barrier at the interface.

Buffering Agents
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 Buffers are employed within pharmaceutical solutions to control
the pH of the formulated product
 Typically pH control is performed:
 To maintain the solubility of the API in the formulated product
 To enhance the stability of products in which the chemical stability of
API is pH-dependent.
 Examples of buffer salts used in pharmaceutical solutions
include:
 Acetates (acetic acid and sodium acetate)
 Citrates (citric acid and sodium citrate)
 Phosphates (sodium phosphate and disodium phosphate)
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Sweeteners
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 Natural sweeteners
 Sucrose;
 soluble in water (vehicle),
 colourless, stable (pH 4-8),
 increases viscosity;
 Arguably the best taste/mouthfeel overall but cariogenic
& calorific → avoid in paediatrics.
 Sorbitol
 (non-cariogenic, non-calorific
- appropriate for paediatric formulations),
 but lower sweetness intensity than sucrose
(so you need more) diarrhoea

Sweeteners,…
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 Artificial sweeteners
 Much more intense sweeteners compared with sucrose
-the levels are much lower (<0.2%).
 Can impart a bitter or metallic after-taste used in
combination with natural sweeteners).
 e.g.
 Saccharin and it’s salts, Aspartame, Acesulfam
 Sucralose – excellent sweetness,
non-cariogenic, low calorie,
wide & growing regulatory acceptability but
relatively expensive.
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Flavouring Agents
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 Supplement and complement a sweetening agent
 Ensures patient compliance (especially in paediatric
formulations a big issue).
 Can be
 natural, e.g. peppermint, lemon oils, Or
 artificial e.g. butterscotch, ‘tutti-frutti’ flavour

Coloring Pharmaceuticals
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 Are added for esthetics;
 to enhance attractiveness.
 Mineral colorants:
 ferric oxide, carbon black, titanium dioxide .
 Vegetable or animal colorants:
 Chlorophyll, Indigo, carotenoides
 90% of the dyes used in the products - synthesized from
derivative of benzene.

Excipients used in
semisolid
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Topical bases
 One of the basic component of ointment, creams and pastes is
the base.
 Topical bases are usually fatty, waxy or synthetic in nature.
 They are intended to soften/melt when applied to the skin.
Bases have two distinct purposes:
oAs a vehicle from which drugs may be absorbed by the skin.
oAs a protective or emollient for the skin.

A. Hydrocarbon bases
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 water-free, and aqueous preparations may be incorporated into
them only in small amounts and then with difficulty.
 Hydrocarbon bases are retained on the skin for prolonged
periods
 act as occlusive dressings
 Hard paraffin
 Soft paraffin
 Liquid paraffin

B. Absorption bases
 Those that permit the incorporation of aqueous
solutions,
 resulting in the formation of water-in-oil emulsions
(e.g. Hydrophilic Petrolatum and Anhydrous lanolin)
 Those that are already water-in-oil emulsions
(emulsion bases) that
 permit the incorporation of small, additional
quantities of aqueous solutions
(e.g. lanolin).
 useful pharmaceutically to incorporate aqueous
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C. Water-Removable Bases
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 May be diluted with water or with aqueous solutions.
 have the ability to absorb serous discharges in
dermatologic conditions
 Stearic acid, beewax and paraffin are the main
oleaginous bases.
 propylene glycol and water representing the aqueous
phase.
 Methylparaben and propylparaben are used to preserve
the ointment against microbial growth.

D. Water-Soluble Bases
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 Contain only water-soluble components
 Because they soften greatly with the addition of water,
 aqueous solutions are not effectively incorporated into
these bases.
 Rather, they are better used for the incorporation of non
aqueous or solid substances.
 PEG are polymers of ethylene oxide and water.
 The chain length may be varied to achieve polymers
 having desired viscosity and physical (liquid, semisolid, or
solid) form.

Suppository bases
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 It remains solid at room temperature but softens,
melts, or dissolves readily at body temperature
 According to bases physical characteristics the
bases can be classified into
(1) fatty or oleaginous bases
(2)water-soluble or water-miscible bases

1. Fatty or oleaginous bases
(a) Cocoa Butter
-Seed of theobroma cacao, Chemically, it is a
triglyceride
-It melts between 30℃ to 36 ℃, an ideal suppository
base
- cocoa butter exhibits marked polymorphism
- Cocoa butter must be slowly and evenly melted
- Substances such as phenol and chloral hydrate
- have a tendency to lower the melting point of cocoa
butter
- solidifying agents like cetyl esters wax (about 20%) or
beeswax (about 4%) may be melted with the cocoa butter to
compensate for the softening effect of the added substance.
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Fatty or oleaginous bases,…
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(b) compounds of glycerin
 composed of mixtures of glycerides of higher saturated
fatty acids
 Such compounds as glyceryl monostearate and
glyceryl monopalmitate are examples of this type of
agent.
 More stable
 Not need of lubricating agents for mold.

2. Water-soluble or water-miscible bases
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A. Glycerinated gelatin
 This base is slower to soften and mix with the physiologic
fluids ,
 therefore provides a more prolonged release
 Must be protected from atmospheric moisture in order for
them to maintain their shape and consistency.
 may have a dehydrating effect and be irritating to the tissues
upon insertion.
 the suppositories may be moistened with water prior to
their insertion reduce the initial tendency of the base to draw
water
 most frequently used in the ppn of vaginal suppositories

B. Polyethylene glycols,PEG
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 The more commonly used being PEG
 200,400, 600,1000,1500,1540, 3350, 4000,6000, and 8000.
 Polyethylene glycol suppositories do not melt at body
temperature but rather
 dissolve slowly in the body's fluids.
 If the polyethylene glycol suppositories do not contain
at least 20% of water to avoid the irritation of the
mucous membranes after insertion,
 they should be dipped in water just prior to use.

1. Systemic Route
2. Local route
ROUTES OF DRUG
ADMINISTRATION
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Classification
A route of administration in pharmacy is the path by which a
drug is taken into the body.
In this route the drug is
applied on the
 skin and
 mucous membrane for the
local action.
1. Systemic Route 2. Local route
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Oral Route (per oral)
 In this route the drug is placed in the mouth and swallowed
 Advantages
 Convenient - Can be self-administered, painless, easy to take
 Cheap - not sterilization
 Variety – tablets, capsules,
 fast, slow release
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Oral Route,…
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 Disadvantages
 May be inefficient - high dose, low solubility (only part of the drug may
be absorbed)
 Food Interaction: Tetracyclines
 Irritation to gastric mucosa,NV, Aspirin and NSAIDs
 Destruction of drugs by gastric acid and digestive juices: Erythromycin
 Unconscious patient - not able to swallow
 Unpleasant test of some drugs: Quinine
 First-pass effect
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Oral Route,…
Hepatic first pass effect
 The hepatic metabolism of a pharmacological agent when it
is absorbed from the gut and delivered to the liver via the
portal circulation.
 The greater the first-pass effect, the less the agent will reach
the systemic circulation when the agent is administered
orally.
e.g Imipramine, Propranolol, Lidocaine
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Sublingual/Buccal route
 Drug is kept in the buccal cavity or under tongue
 where it disintegrates and absorption occurs in the mouth.
 Buccal -often harder – slower absorption
 4 hour disintegration
 Sublingual - softer - faster release
 2 min disintegration (Nitroglycerin)
 Examples - nitroglycerin, steriods, nicotine (chewing gum)
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Sublingual/Buccal route,…
 Advantages
Avoid first pass effect: direct to the blood (liver is by-
passed )
Rapid absorption: good blood supply to the area
Drug stability: not destroyed by the enzymes and acids
 Disadvantages
Inconvenient
Holding the dose in the mouth
Advantages lost if swallowed
Small dose limit: Small size is required to keep the drug in
the mouth
Unpleasant taste of some drugs
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Rectal Route
 By Suppository or Enema
E.g. aspirin, theophylline, chlorpromazine
 Advantages
By pass liver: Following absorption from the rectum, the
therapeutic agent enters the haemorrhoidal veins.
Blood from the upper haemorrhoidal vein enters the
portal vein,
Blood in the middle and lower haemorrhoidal veins
enters the general circulation.
Useful - children, non po
If patient is having nauseous or vomiting
 Disadvantages
Erratic absorption
Not well accepted
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Parenteral: Intravenous
 Injection into a peripheral vein over 1 to 2 minutes (bolus) or
longer as an infusion
 Advantages
Rapid response, Total dose ►by-passes absorption stage
larger doses by infusion
Can be given to unconscious patients
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Intramuscular
 In this route of administration the drug is given into the
muscles with the help of injection
 Advantages
Larger volume than SC
Depot or sustained effect is possible
 Disadvantages
Trained personnel
Site affects absorption: deltoid
Absorption may be erratic or incomplete
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Subcutaneous
In this route of administration the drug is given into the
subcutaneous layer with the help of injection(Just under the skin)
 Advantages
Can be given by the patient e.g. in the case of insulin
Absorption slow but generally complete
Massage or heat, Vasoconstriction
 Disadvantages
Painful
Tissue damage from irritant drugs
Maximum of 2 ml injection
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Inhalation
 In this class the drug is administered
 To the blood without going to the GIT
 Not administered with the help of injections
Local effect: bronchodilator
Systemic effect: general anesthesia
 Advantages
By pass liver
Absorption of gases efficient and rapid
 Disadvantage
Solids and liquids excluded if > 20 mincron and exhaled
if < 0.5 micron
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Local/Topical
 In this route the drug is applied on the skin and mucous
membrane for the local action
Dermal - Rubbing in of oil or ointment (local effect)
eg eye drops, antiseptic, sunscreen
Transdermal - Absorption of drug through skin (systemic
effect)
e.g. nitroglycerine ointment, scopolamine
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Local/Topical,…
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 Advantage
Stable blood levels
No first pass metabolism
 Disadvantage
Toxicity from topical absorption
Burn patients
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Other ROA’s
Intra-nasal - small dose, avoid first pass
Intra-arterial - cancer chemotherapy, localised delivery
Others routes with limited systemic absorption but with local
utility include:
Ocular
Aural
Vaginal
Urethral
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Onset of Action
Intravenous 30-60 seconds
Intraosseous 30-60 seconds
Inhalation 2-3 minutes
Sublingual 3-5 minutes
Intramuscular 10-20 minutes
Subcutaneous 15-30 minutes
Rectal 5-30 minutes
Oral 30-90 minutes
Topical/transdermal (topical): variable (minutes to hours).
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Ch1. intro pharmaceutical

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