TOPICAL SOLUTIONS

Dr. Wasfy Obeidat 1

 TOPICAL SOLUTIONS
► LEARNING OBJECTIVES
 Basic knowledge of topical solutions
 Be familiar with different topical solutions
 Know the composition and use of most widely
used topical solutions
 Be familiar with Douches, Enemas and
Collodions
 Otic solutions and compositions

Dr. Wasfy Obeidat 2

TOPICAL SOLUTIONS THIMEROSAL TOPICAL
SOLUTION
► What is a topical solution? Merthiolate Solution
A solution that is applied on the body surface or
cavity. Topical solutions are of two general types: ► Composition
 Thimerosal Topical Solution contains 0.1%
► Regular topical Solutions: Topical solutions thimerosal (Sodium salt of ethyl mercury
that employ an aqueous vehicle. thiosalicylic acid, C9H9NaO2S) .
► Other components include
► Topical tincture: Topical tinctures  Sodium borate
characteristically employ an alcoholic vehicle.
 Ethylene diamine
► These tincture cause stinging sensation.
 Monoethanolamine
► Use
► Composition of a typical topical solution
 All topical solutions are self-preserved and  Used topically for its bacteriostatic and mild
fungistatic properties.
contain a dye.
 antioxidants, humectants, scents, viscosity ► Storage
inducing agents  The solution is affected by light and must
be maintained in light-resistant containers.
► Topical solutions are available in
 Glass bottles having an applicator tip
 Plastic squeeze bottles

Dr. Wasfy Obeidat 3

► Burow’s Solution
Aluminum oxide to acetic acid at 1:3.52
► Modified Burow’s Solution (Aluminum
Subacetate Topical Solution)
Aluminum oxide to acetic acid is 1:2.35.
► Stronger than aluminum acetate
topical solution.
 Use
► Used as an ingredient in various
types of dermatological preparations,
as lotions, creams, and pastes.
► Widely applied topically as an
astringent wash or wet dressing after
dilution with 10 to 40 parts of
water
► Modified Burrow`s is used in the
preparation of the aluminum acetate
topical solution.
Dr. Wasfy Obeidat
► Composition
 Contain not less than 140 mg of
Ca(OH)2 in each 100 ml of
solution.
► Storage
 The solution should be stored in
tightly stoppered containers to deter
the absorption of carbon dioxide.
 Should be kept in a cool place.
► Use
 Only the clear supernatant liquid is
dispensed.
 The solution is categorized as an
astringent.
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► Compositions
 Coal tar topical solution is an alcoholic
solution containing 20% of coal tar and
5% of polysorbate 80.
► Preparations
 It is prepared by mixing the coal tar with
two and a half times its weight of washed
sand, adding the polysorbate 80 and
alcohol, and then macerating the mixture
for 7 days in a closed vessel with frequent
agitation followed by filtration and
adjustment to the proper volume with
alcohol.
 The final alcoholic content is between
81 and 86% ethyl alcohol.
► Use
 Antieczematic and for a wide variety of
chronic skin conditions.
Dr. Wasfy Obeidat
► Composition
 Hydrogen peroxide topical Solution
contains between 2.5 and 3.5% (w/v)
of hydrogen peroxide, H2O2.
► Storage
 It usually deteriorates upon long
standing with the formation of oxygen
and water, acetanilide, is used to
retard the solution’s decomposition
 Decomposition is enhanced by light
and by heat.
► Use
 Local anti-infective for use topically on
the skin and mucous membranes.
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 CHLORHEXIDINE
GLUCONATE SOLUTION

► Composition
 Chlorhexidine gluconate 4% (Hibiclins,
Stuart). ► Composition
 Chlorhexidine gluconate, 0.12%  A chemical complex of iodine with
(Peridex, Procter & Gamble) polyvinylpyrrolidone .
► Use
 Surgical scrub, hand wash and general  The povidone-iodine complex contains
skin cleanser approximately 10% of available iodine
 Peridex is used as antiplaque/antigingivitis and slowly releases it when applied to
drug with antimicrobial activity. the skin.
► Use
► Undesirable effects
 Surgical scrub
 Yellow-brown stain on the teeth and
tongue.  Nonirritating antiseptic solution.
 Increased with consumption of tannins
containing substances, e.g., tea, red wine.

Dr. Wasfy Obeidat 6

 DOUCHES
► Douches
 Douches are aqueous
solutions directed into cavity
of the body, it functions as a
cleansing and antiseptic
agents.
 Douches could be of eye,
pharyngeal, nasal and
vaginal.
 An eye douche is used to
remove particles and
discharges from the eyes.
 Pharyngeal douches are
used to prepare the interior
of the throat for an
operation and cleanse it in
supportive condition.
Dr. Wasfy Obeidat
 Vaginal douches are most
common type of douche and
are used for cleaning the vagina
and hygienic purposes.
► Forms of Douches:
 A unit package is designed to
contain the appropriate amount
of powder to prepare the
specified volume of douche
solution.
 The bulk powders are utilized
by the teaspoonful or
tablespoonful amounts in the
preparation of the desired
solution.
 Tablets for preparing solutions
are available.
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 VAGINAL DOUCHES

► Composition of a Vaginal
Douche
 Among the components of vaginal
douche powders are the following
► Boric acid or sodium borate.
► Astringents, as potassium, alum,
ammonium alum, zinc sulfate.
► Antimicrobials, as oxyquinoline sulfate,
povidone-iodine.
► Quaternary ammonium compounds, as
benzethonium chloride.
► Sodium lauryl sulfate.
► Sodium perborate.
► Salts, as sodium citrate, sodium chloride
► Aromatics, as menthol, thymol,
eucalyptol, methyl salicylate, phenol,

Dr. Wasfy Obeidat Applicator for douches8

 RECTAL SOLUTIONS
► ENEMAS
 Rectal injections employed to evacuate the bowel, influence
the general system by absorption or to affect a local disease.

 Enemas could be retention or evacuation enemas

► Retention enemas
 Administered rectally for the local effects of the medication
(e.g., hydrocortisone) or for systemic absorption (e.g.,
aminophylline).
► Evacuation Enemas
 Rectal enemas are used to cleanse the bowel.
Composition
 Solutions of sodium phosphate
 Sodium biphosphate,
 Glycerin
 Docusate potassium
 Light mineral oil.
Dr. Wasfy Obeidat 9
 TINCTURES
IODINE TINCTURE THIMEROSAL TINCTURE
► Composition: ► Composition
 Prepared by dissolving 2% of iodine  1% thimerosal in the vehicle of the
crystals and 2.4% of sodium iodide tincture composed of water, acetone,
in an amount of alcohol equal to half and about 50% alcohol.
the volume of tincture to be prepared ► Storage
and then diluting the solution to volume  Must be manufactured and stored in
with sufficient purified water. glass or suitably resistant containers.
► Use:  Monoethanolamine and
 Local anti-infective agent applied topically ethylenediamine are used as
to the skin. stabilizers
► Storage: ► Use
 Household antiseptic for application
 The tincture should be stored in tight
topically on the skin in abrasions and
containers to prevent loss of alcohol.
cuts
 Preoperative preparation of patients
for surgery.

Dr. Wasfy Obeidat 10

 COMPOUND BENZOIN TINCTURE
► Also called Tincture Friar’s Balsam;  Compound tincture of benzoin
Persian Balsam; Turlington’s Balsam serves as a delivery vehicle of
of Life podophyllum in the treatment
of venereal warts.
► Composition and Preparation
► Storage
 Prepared by the maceration in
alcohol of 10% benzoin and  Compound benzoin tincture is
best stored in tight, light-
lesser amounts of aloe, storax resistant containers.
and tolu balsam (fragrant  Exposure to direct sunlight or
exudations from certain trees). to excessive heat should be
avoided.
► Use
 Used to protect and toughen
skin in the treatment of
bedsores, ulcers, cracked
nipples, and fissures of the lips
and anus.
 Used as an inhalant in bronchitis
and other respiratory conditions Balsams are exudates of tree
Dr. Wasfy Obeidat 11
 COLLODIONS
► Composition
 Liquid preparations composed of
pyroxylin dissolved in a solvent
mixture usually composed of
alcohol and ether with or without
added medicinal substances.
► Pyroxylin is obtained by the
action of a mixture of nitric
and sulfuric acids on cotton
and consists chiefly of cellulose
tetranitrate.
► It is frequently available
commercially moistened with
about 30% alcohol or other
similar solvent.
 The products must be clearly
labeled “For External Use Only”.
 There are three types of
collodions:
Dr. Wasfy Obeidat
REGULAR COLLODION
► Composition
 Collodion is a clear or slightly
opalescent, viscous liquid prepared by
dissolving pyroxylin (4% w/v) in a 3:1
mixture of ether and alcohol.
► Storage
 The solution is highly volatile and
flammable and should be preserved in
tight containers at a temperature not
exceeding 30°C remote from fire.
► Use
 Form a protective film on application
to the skin and the volatilization of the
solvent.
 The film is useful in holding the edges
of an incised wound together.
 Its presence on the skin is
uncomfortable due to its inflexible
nature.
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FLEXIBLE COLLODION
► Composition:
 Flexible Collodion is prepared by adding
2% of camphor and 3% of castor oil to
collodion.
 The castor oil renders the product flexible,
permitting its comfortable use over skin
areas that are normally moved, such as
fingers and toes.
 The camphor makes the product
waterproof.
► Use:
 Physicians frequently apply the coating
over bandages or stitched incisions to
make them waterproof and to protect
them from external stress.
Dr. Wasfy Obeidat
► SALICYLIC ACID
COLLODION
Composition
 Salicylic acid collodion is a 10% solution
of salicylic acid in flexible collodion.
► Use
 Used for its keratolytic effects, especially
in the removal of corns a from the toes.
► Instruction for patients
 The product should be applied one drop
at a time onto the corn or wart allowing
time to dry before the next drop is
added.
 Because salicylic acid can be irritating to
normal, healthy skin every attempt must
be made to ensure application directly
onto the corn or wart.
 A useful preventive measure is to line
the adjacent healthy skin with some
white petrolatum prior to application of
the product.
 Proper tightening and storage of the
product after use is an absolute
necessity because of the volatility of the
vehicle.
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 OTIC SOLUTIONS
► What are Otic Solutions?
 Otic solutions are preparations that are
used for the treatment of different ear
condition, especially that require local
effect.
 Ear preparations are usually placed in
the ear canal by drops or in small
amounts for the removal of excessive
cerumen (ear wax) or for the treatment
of ear infections.
 Otic solutions contains buffers, solvent
and preservatives
What is cerumen removing solution?
Surfactants, vegetable oils, light
mineral oils are used as cerumen
removing solutions.
Example:
Debrox Drop (Carbamide peroxide
in glycerin/propylene glycol.
Cerumex Drop: triethnolamine
polypeptide oleate formulated in
propylene glycol.

► What is cerumen and how does it

form?
 Cerumen is a combination of the
secretions of the sweat and
sebaceous gland of the external
auditory canal.
 Form a sticky semisolid which hold shed
epithelial cells, fallen hair, dust and
other foreign bodies that make their
way into the ear canal

Dr. Wasfy Obeidat 14

 OTIC SOLUTIONS
► Anti-infective, Anti-inflammatory, and Analgesic Ear
Preparations
 Drugs used topically in the ear for their antiinfective activity
► Chloramphenicol,
► Colistinsulfate,
► Neomycin,
► Polymyxin B sulfate
► Nystatin,
 Formulated into eardrops (solutions or suspensions) in a vehicle of
anhydrous glycerin or propylene glycol which are Viscous and
hygroscopic vehicles.

Dr. Wasfy Obeidat 15

DR. WASFY OBEIDAT 1
 OPHTHALMIC SOLUTIONS
► LEARNING OBJECTIVES
 Basic knowledge of the anatomy and physiology of eye
 Recognize barriers and factors affecting ophthalmic drug
absorption
 Understand of Ophthalmic formulations
 Be familiar with the desired properties of an ophthalmic
preparation
 Basic knowledge of different ophthalmic formulations
 Be familiar with additives and packaging of ocular
preparations

DR. WASFY OBEIDAT 2

 OPHTHALMIC PREPARATIONS
 Pharmaceutical preparations
that are applied topically to the
eye to treat surface or
intraocular conditions,
including:
► Infections of the eye or eyelids
due to bacterial, fungal and
viral pathogens
► Allergic or infectious
conjunctivitis or
► Dry-eye due to an inadequate
production of fluids bathing the
eye.
► In treating certain ophthalmic
conditions such as glaucoma.

DR. WASFY OBEIDAT 3

 OPHTHALMIC PREPARATIONS
Eye Anatomy and Physiology
► Optic nerve (2nd cranial nerve)
► Spherical in shape (diameter ~
2.5cm)
► Fatty tissue for protection.

Structure
A. Layers:
- The outer fibrous layer: Sclera (white
fibrous tissue) and Cornea
- The middle vascular layer (Choroid),
ciliary body and the iris
- The inner nervous layer: The Retina
A. Inside
- Eye ball
- Lense
- Aqueous humor
- Vitreous body (humor) DR. WASFY OBEIDAT 4
 OPHTHALMIC PREPARATIONS
Cornea- Avascular
- Thin epithelial layer continuous
with the conjunctiva at the cornea- -Paracellular: mainly for ions
sclerotic junction.
(barrier for ionic and hydrophilic
drugs)
- Posterior surface: single thick
endothelial layer with some
lipophilic character.
(but the permeability resistance is
based on the size).
-Cornea is major route for most
ophthalmic drugs penetration by
diffusion transcellular (mostly).
penetration.
Sclera
-Made of the same collagen as the
cornea but more organized structure,
It is minor route for drug
penetration.

- The main bulk is the Stroma (90%)

in the middle and made of
collagen, proteins and
mucopolysacch, salts and water
(78%).
DR. WASFY OBEIDAT 5
 OPHTHALMIC PREPARATIONS
Aqueous humor
- A watery fluid, about 300 ML
filling the anterior chamber.
- Secreted by ciliary body
- Contributes much to the IOP
Lacrimal glands
-Tears to clean and lubricate
-About 7-10 µl
(Max vol in eye): 30 µl
Watery of pH 7.4 (6.9 - 7.5)

Conjunctiva - Isotonic (bicarbonate and NaCl)

- A thin, clear layer of skin
covering the front of the eye - With lysozymes and proteins
(except the cornea), including
the sclera and the inside of the
eyelids (upper and lower)
- It is a minor route for drug
penetration

DR. WASFY OBEIDAT 6

 OPHTHALMIC PREPARATIONS
Competing Factors: Limitations:
1. Drainage via nasolacrimal - Short precorneal residence
system to GI tract time (high clearance rates)
Stimulated by  vol in eye > - Poor drug penetration into
10l the ocular tissue
 systemic effects and taste - When absorption occurred,
  drop size ( conc) may it lasts shortly
 abs
2. Absorption into conjunctiva
(large SA, very vascular)
circulation
3. Transcorneal absorption

DR. WASFY OBEIDAT 7

DR. WASFY OBEIDAT 8
OPHTHALMIC SOLUTIONS

DR. WASFY OBEIDAT 9

► What is an ophthalmic suspension?
 When drug is dispersed in the
solvent and exist in fine particulate
form, the formulation is called
ophthalmic suspension (95% of the
particles should have a size 10 m or
less).

 Drug is present in finely divided in

an aqueous vehicle containing
suitable suspending and dispersing
agents.

 The particles in ophthalmic

suspensions must undergo
significant dissolution within the
residence time of the dose.

is applied to the eye. DR. WASFY OBEIDAT 10

DR. WASFY OBEIDAT 11
DR. WASFY OBEIDAT 12
DR. WASFY OBEIDAT 13
DESIRED PROPERTIES OF OPHTHALMIC
PREPARATIONS

DR. WASFY OBEIDAT 14

 Sterile gown Air flow in laminar hood

Laminar air flow hood

DR. WASFY OBEIDAT 15
DR. WASFY OBEIDAT 16
STABILITY

DR. WASFY OBEIDAT 17

BUFFERS AND pH ADJUSTING AGENTS

DR. WASFY OBEIDAT 19

 BUFFERS AND pH ADJUSTING AGENTS

► Sorensen’s Modified Phosphate Buffer

 Sorensen’s phosphate buffer is made using two stock solutions: one
acidic, containing NaH2PO4, and one basic, containing
Na2HPO4.
 These buffer solutions are not isotonic.
 Sorensen's Modified Buffer has a large buffer capacity and should
not be used outside the pH range of 6.5-8.0.

► Amount of buffer solution to use

 The buffer solution is often used as the tonicity adjustor for the
ophthalmic solution.
 One general rule states that the concentration of the buffer should
be 10 times that of the drug, the concentrations of both expressed
in molar quantities.

DR. WASFY OBEIDAT 20

► Tonicity adjusting agents that are added to ophthalmic
solution include:
 Sodium chloride,
 Sodium nitrate,
 Sodium sulfate, and
 Dextrose.

DR. WASFY OBEIDAT 21

► Preservatives
 Agents that are used as preservatives in ophthalmic preparations include
the following substances.
 Before adding a preservative, patient sensitivity, compatibility of the
preservative with all other ingredients in the formulation should be
checked.

► Antioxidants
 If oxidation is a problem, an antioxidant may be necessary or
recommended.

DR. WASFY OBEIDAT 22

 Polysorbate 80 1.0%
 Polysorbate 20 1.0%

DR. WASFY OBEIDAT 23

DR. WASFY OBEIDAT 24
► Glass Dropper Bottles
 The glass dropper bottles are
used for products that are
extremely sensitive to
oxygen or contains
permeable components that
are not sufficiently stable in
plastic.
 Glass containers remain a
convenient package material for
extemporaneous preparation of
ophthalmic solutions.
 Type 1 glass should be
used. The container may be
sterilized by autoclaving.
 Droppers should be
presterilized and packaged in a
convenient blister pack.

accidental or purposeful, has

DR. WASFY OBEIDAT occurred. 25
 The normal volume of tear fluid retained in
the cul-de-sac of the human eye is about 7-10 l.
 An eye that is maintained in a non-blinking state
can accommodate a maximum of about 30 l of
fluid but when blinked can retain only about
7-10 l.
 Because the capacity of the eye to retain liquid and
semisolid preparations is limited, topical
applications are administered in small
amounts; liquids drop-wise and ointments as
a thin ribbon applied to the margin of the eyelid.
 Larger volumes of liquid preparations may be used
to flush or bath the eye.
 The optimal volume to administer, based on eye
capacity would be 5 to 10 L.
DR. WASFY OBEIDAT 26
DR. WASFY OBEIDAT 27
DR. WASFY OBEIDAT 28
SOLUTION FORMULATION

DR WASFY OBEIDAT 2020

 ORAL SOLUTIONS
• LEARNING OBJECTIVES
– Understand the concept of oral solution type of dosage form
– Know the advantages and disadvantages of oral solutions.
– Be familiar with the excipients used in oral solution.
– Basic principles for the preparation of syrup, small and large scale.
– Be familiar with compounding of syrup.

DR WASFY OBEIDAT 2020

 Types of solutions
- Rectal preparations:
• NON-STERILE
Enemas
- Oral:
Syrups, Elixirs, Tinctures,
Linctuses, Mixtures and - Others (intermediate):
draughts. Spirits (solutions of aromatic
materials in alcoholic solvents),
- Topical: Aromatic Waters
(solutions of aromatic materials
Ear drops, Inhalations, in aqueous solvents), gels
Mouthwashes and
Gargles, Nasal drops and
sprays • STERILE SOLUTIONS
- Parenteral:
- Liquids for cutaneous injections,
application: Infusions (drips)
Lotions, Liniments, Paints
Collodions - Irrigations
DR WASFY OBEIDAT
-Eye2020
Drops
 Guidelines for solubility
• The solubility of a substance at a given temperature and
pressure is constant, however the rate of solution (which is
called dissolution rate) depends on:
- Particle size
- Extent of agitation

• The introduction of halogen atoms into a molecule tends to

decrease water solubility. For example, the solubility of CCL4<
CHCL3< CH2Cl2 (Increase in molecular weight without a
proportionate increase in polarity).

• Molecules with large molecular weight are generally water

insoluble.

DR WASFY OBEIDAT 2020

 ORAL SOLUTIONS
• What is an oral solution?
– Liquid preparation intended for oral
use
– They contain one or more
therapeutically active ingredients
dissolved in water or water-
cosolvent system
– Contain inactive ingredients to
improve
• Palatability,
• stability,
• Aesthetic property
– Some contain high concentration of
sucrose or other sugars (e.g. syrup
and elixir).

DR WASFY OBEIDAT 2020

ADVANTAGES OF ORAL SOLUTIONS

what are the advantages of oral

solutions?

DR WASFY OBEIDAT 2020

 ADVANTAGES OF ORAL SOLUTIONS
• Easy to Swallow: therefore particularly acceptable for pediatric
and geriatric use.

• Immediate Absorption: thus the therapeutic response is faster.

• Uniformity: A solution is a homogenous system and therefore

the drug will be uniformly distributed throughout the preparation.

• Reduced Side effects: Some drugs, including aspirin and

potassium chloride, can irritate and damage the gastric mucosa
particularly if localized in one area as often occurs after the
ingestion of a solid dosage form.
– Irritation is reduced by administration of a solution of a drug
because of the immediate dilution by the gastric contents.

DR WASFY OBEIDAT 2020

 ADVANTAGES OF ORAL SOLUTIONS

what are the disadvantages of oral

solutions?

DR WASFY OBEIDAT 2020

 DISADVANTAGES OF ORAL SOLUTIONS
• Bulky
– Liquids are bulky and therefore inconvenient to transport and
store. If breakage of the container should occur the whole of
the product is immediately and irretrievably lost.

• Instability
– The stability of ingredients in aqueous solution is often poorer
than if they were formulated as a tablet or capsule,
particularly if they are susceptible to hydrolysis.

• Microbial Contamination
– Solutions often provide suitable media for the growth of micro-
organisms and therefore require the incorporation of a
preservative.

DR WASFY OBEIDAT 2020

• Dose Inaccuracy
– Accurate dosage usually depends on the
ability of the patient to use a 5 ml spoon or,
more rarely, a volumetric dropper.

• Unpleasant Taste
– The taste of a drug, which is usually
unpleasant, is always more pronounced
when in solution than when in a solid form.

DR WASFY OBEIDAT 2020

 COMPONENTS/INGREDIENTS OF ORAL
SOLUTIONS

• The main components in an oral solution are

– Active ingredient
– Vehicles
– Sweeteners
– Flavors
– Colors
– Preservatives
– Buffers
– Antioxidants
– Perfumes

DR WASFY OBEIDAT 2020

 VEHICLES
• Water
– Water is the most widely used solvent for use as a
vehicle for pharmaceutical products because of its lack
of toxicity, physiological compatibility and its ability to
dissolve a wide range of materials.

– Ordinary drinking water obtained from the tap is not

generally acceptable for the manufacture of most
aqueous pharmaceutical preparations or for
extemporaneous compounding of prescription since it is
IMPURE, but can be used in preparing certain products
for external use. It must also meet the regulations with
respect to bacteriologic purity.

DR WASFY OBEIDAT 2020

Purified Water, USP, H2O
• Purified Water, USP is obtained by distillation, ion-exchange
treatment, reverse osmosis
• Solid impurities not more than 0.001% of the residue (1 mg of
solids per 100 ml of water).
• Employed in preparation of aqueous dosage forms except for
injections.
Distillation method
• Usual starting material is the drinking water.
• The first portion of aqueous distillate (10-20%), must be
discarded (contains foreign volatile substances).
• The last portion of water remaining in the apparatus, about
10%, must be discarded and not subjected to further
distillation (decomposition of the remaining solid impurities to
volatile substances).
DR WASFY OBEIDAT 2020
Ion Exchange Method
• Passage of water through a column of exchangers consisting
of water-insoluble synthetic polymerized phenolic, carboxylic,
amino, or sulfated resins of high molecular weights.
• Resins are mainly two types: Cation or acid exchangers,
and Anion or base exchangers
• Advantages over distillation:
– Elimination for the requirement of heat and thus costly and
troublesome maintenance of the more complex distillation
apparatus
– Simpler equipment and nature of the method
– Ease of operation
– Minimal maintenance.
– More mobile facility

DR WASFY OBEIDAT 2020

Reverse Osmosis
• In osmosis, a lower-concentrate solution will filter its solvent to
the higher concentrate solution. In reverse osmosis, we are
(literally) just reversing the process, by making our solvent filter
out of our high concentrate into the lower concentrate solution.
• Reverse osmosis takes place when pressure applied to a highly
concentrated solute solution causes the solvent to pass through
a membrane to the lower concentrated solution, leaving a higher
concentration of solute on one side, and only solvent on the
other.
• Reverse osmosis removes particles smaller than 0.001 m, virtually
all viruses, bacteria, pyrogens, and organic molecules and 90 to
99% of ions

DR WASFY OBEIDAT 2020

• Alcohol, USP, Ethyl alcohol, Ethanol, C2H5OH

– Next to water, alcohol is the most useful solvent in

pharmacy.
– Miscible with water in all proportions
– It is used as a primary solvent for many organic
compounds.
– Together with water it forms a hydroalcoholic mixture that
dissolves both alcohol-soluble and water-soluble
substances.
– It is also used in liquid products as an antimicrobial
preservative alone or as a co-preservative with parabens,
benzoates, sorbates, and other agents.

DR WASFY OBEIDAT 2020

Concerns:
• Undesired pharmacologic and potential toxic effects when
ingested particularly in children.
• FDA restricts the use of alcohol and includes appropriate
warning in the labeling for OTC oral drug products.

Age (years) Recommended limit

Under 6 0.5%.
6-12 5.0%
Over 12 10%

Types of Alcohol Percentage by volume

USP 94.9-96.0%
Dehydrated 99.5%
Diluted, NF 49%
Rubbing 70%

DR WASFY OBEIDAT 2020

• Glycerin, USP, (Glycerol), CH2OH.CHOH.CH2OH
– Glycerin is a clear syrupy liquid with a sweet taste.
– Glycerin has preservative qualities and is often used as a
stabilizer and as an auxiliary solvent in conjunction with water or
alcohol.
– Solutes are slowly soluble in it because of its high viscosity
unless it is rendered less viscous by heating

• Propylene Glycol, USP, CH3CH(OH)CH2OH

– A viscous liquid
– Miscible with water and alcohol.
– Frequently substituted glycerin in modern pharmaceutical formulations.

• Isopropyl Rubbing Alcohol (70%)

- Employed as rubefacient externally
- Skin disinfectant prior to injections (91%),
- Vehicle for topical preparations.
DR WASFY OBEIDAT 2020
 FLAVORS
• Why do we need to add flavor?
– Flavors are added to oral solutions to
improve patient acceptance of the
preparation.
– Flavors may be added to improve the
palatability of a bland preparation or
to mask the unpleasant taste of an
active ingredient.

Baby's bitter taste

reaction

DR WASFY OBEIDAT 2020

 HOW DO WE SELECT A FLAVOR?
• Flavor preference is somewhat age-related.
• Sweet, fruity, and bubblegum-type flavors for children
• Chocolate, coffee, licorice, maple, or butterscotch for adults.
• Personal preference; for example, some patients love the taste
of chocolate while others dislike it.
• Be aware that some patients associate bitter taste with drug
potency and effectiveness!!!!.

DR WASFY OBEIDAT 2020

 DETERMINATION OF TASTE OF A DRUG
• Sour taste: is the result of H+ ions and is proportional to the
hydrogen ion concentration and the compound’s lipid solubility

• Salty taste: is associated with inorganic or low-molecular-

weight ionic compounds, such as sodium chloride (thus the
name "salt"), ammonium chloride, and sodium salicylate.

• Bitter taste: When one of the ions in a salt is a high-molecular-

weight compound, such as diphenhydramine HCl, the taste is
usually bitter. Free bases and amides such as caffeine,
amphetamine, and codeine are also bitter.

• Sweet taste: is most often associated with the low-molecular-

weight polyhydroxy compounds, such as sucrose, sorbitol,
and mannitol.
– Imides such as saccharin, and amino acid combinations
such as those in aspartame are very sweet and widely
used as sweeteners.
DR WASFY OBEIDAT 2020
 FLAVORS
• Salty • Sweet
– Apricot – Vanilla
– Butterscotch – Fruits
– Licorice – Berries
– Peach
– Vanilla • Sour
– Citrus
– Fruits
• Bitter
– Licorice
– Anise – Raspberry
– Chocolate
– Mint
– Fruit
– Wild Cherry

DR WASFY OBEIDAT 2020

 SWEETNERS
• Why do we need to add sweeteners?
– sweeteners are added to oral
solutions to improve patient
acceptance of the preparation.

Baby's bitter taste

reaction

DR WASFY OBEIDAT 2020

 SWEETENERS
• Desirable properties of sweeteners include:
– Colorless
– Odorless
– Soluble in water at the concentration needed for
sweetness
– Pleasant taste with no bitter after-taste
– Chemically stable at normal temperatures of use and
storage
– Stable over a broad pH range
– Noncarcinogenic, and nontoxic.

DR WASFY OBEIDAT 2020

 SWEETENERS
• Polyhydroxy compounds
– Sucrose
– Sorbitol
– Mannitol

• Saccharin compounds
– Saccharin
– Saccharin sodium, also known as soluble
saccharin

• Aspartame
– Aspartame is a combination of two amino
acids L-aspartic acid and L-phenylalanine in
its methyl ester form.
– Not stable to heat.

DR WASFY OBEIDAT 2020

SWEETENERS

DR WASFY OBEIDAT 2020

 COLORS
• Colors are substances added to drug products solely for
the purpose of imparting color and thus enhance appeal.
– They must be nontoxic and inactive pharmacologically
– They may not be added to injectable or ophthalmic
preparations
– They may not be employed to disguise poor product
quality

• Colors are added to improve patient acceptance of a

product.
– The color added to an oral product should coincide with
the flavor given to the product; for example, cherry-
flavored products should be colored red and orange-
flavored productsDRshould be colored
WASFY OBEIDAT 2020 orange.
 COLORS
• The colors used in pharmaceutical products are either natural
colors or synthetic dyes.

• Natural colors that are used in drug products fall into two
classes:
• Mineral pigments: Red Ferric Oxide, Titanium Oxide, and
carbon black.
• Plant pigments: indigo, saffron, and beta-carotene

• Synthetic dyes
– Synthetic dyes are chemically synthesized.
– Dyes used in foods, drugs, and cosmetics must be certified
by the Food and Drug Administration for such use.
• FD&C dyes may be used in foods, drugs, and cosmetics.
• D&C dyes are certified for use in drugs and cosmetics
• External D&C dyes are restricted for use in externally
applied drugs and cosmetics.
DR WASFY OBEIDAT 2020
 VISCOSITY INDUCING AGENTS

• Why do we add viscosity

inducing agents to solutions?

DR WASFY OBEIDAT 2020

 VISCOSITY INDUCING AGENTS
• Viscosity inducing agents are added
– To increase the palatability of oral liquid
– To achieve desirable mouth feel.
– To improve perceived flavor of oral liquids
– Example of common viscosity inducing agents
• Methylcellulose
• Carboxymethylcellulose
• Hydroxypropyl cellulose
• Acacia
• Tragacanth gum

DR WASFY OBEIDAT 2020

 PRESERVATIVES
• Preservatives are added to prevent microbial contamination
– Among the preservatives commonly used with the usually
effective concentrations are:
• Benzoic acid (0.1 to 0.2%)
• Sodium benzoate (0.1 to 0.2%)
• Methyl-, propyl-, and butylparabens (0.1%).

• Syrups can also be preserved by

– By the maintenance of a high concentration of sucrose as a
part of the formulation.
– Storage at low temperature

DR WASFY OBEIDAT 2020

 OTHER EXCIPIENTS

• Buffers
– Maintain pH to protect the drug from pH
related instability.
• Antioxidant
– Used to prevent degradation due to oxidation

• Perfumes
– Add to give a particular smell to the product

DR WASFY OBEIDAT 2020

 TYPES OF ORAL SOLUTIONS

• Main categories of oral solutions in the

market:
– Syrups
– Elixir
– Dry mixture for solution

DR WASFY OBEIDAT 2020

 SYRUPS
• What is a syrup?
– Syrups are concentrated, aqueous preparations of a sugar or
sugar-substitute with or without flavoring agents and
medicinal substances.
– Syrups containing flavoring agents but not medicinal
substances are called nonmedicated or flavored vehicles
(syrups).

• Sucrose and non-sucrose based syrups

– Sucrose is the sugar most frequently employed in syrups,
other sugars is dextrose.
– Most syrups contain a high proportion of sucrose, usually 60
to 80% of sucrose.
– Non-sugars such as sorbitol, glycerin and propylene glycol
may be used. For example, Sorbitol solution, USP contains
64% by weight sorbitol.
DR WASFY OBEIDAT 2020
 SYRUPS
• The official syrup (Syrup, NF) has a specific gravity of
1.313 g/ml which means that each 100 ml of the syrup
weigh 131.3 g. Because 85 g of sucrose are present, the
weight of the purified water is 46.3 g. The solubility of
sucrose is 1g in 0.5 ml water. Thus only 3.8 ml of water is
excess in 100 ml syrup. This excess is not enough to be
amenable to the growth of microorganisms and it keeps the
syrup physically stable in varying temperatures.

• Concentrated sugar solutions are resistant to microbial

growth of microorganisms because of the unavailability of
water required for the growth of microorganisms.

DR WASFY OBEIDAT 2020

• Syrup is stable and resistant to crystallization and microbial
growth and requires no additional preservation if it is to be
used soon.

• If the syrup were completely saturated with sucrose, in cool

storage some sucrose might crystallize from solution and
by acting as a nuclei, initiate a chain reaction that would
result in separation of an amount of sucrose
disproportionate to its solubility at the storage temperature.
The syrup would be unsaturated and suitable for microbial
growth.

DR WASFY OBEIDAT 2020

Antimicrobial preservatives
• The amount of a preservative required varies
with:
– Proportion of water available for the growth.
– The nature an inherent preservative activity of some
formulation additives (flavoring oils).
– The capability of the preservative itself.
• Commonly used preservatives in syrups

Preservative Effective Concentration

Benzoic acid 0.1-0.2%
Sodium benzoate 0.1-0.2%
Combinations of methylparabens, 0.1%
propylparabens and butylbarabens
Alcohol 15-20%
37
 PREPARATION OF SYRUPS
• Syrups are most frequently prepared by several
methods, depending on the physical and chemical
characteristics of the ingredients:

• Solution with the aid of heat

– Sugar is generally added to the purified water,
and heat is applied until solution is effected.
– Heat-stable components are added to the hot
syrup
– Mixture is allowed to cool.
– Heat-labile agents or volatile substances, such
as volatile flavoring oils, are generally added to
the syrup after the solution of the sugar is
effected by heat, and the solution is rapidly
cooled to room temperature.
– Caution must be exercised against becoming
impatient and using excessive heat. Water jacketed
• Sucrose, a disaccharide, may be hydrolyzed mixers used to
(inverted) into monosaccharides, dextrose prepare syrups
(glucose), and fructose (levulose).
DR WASFY OBEIDAT 2020
 PREPARATION OF SYRUPS
• The speed of inversion is greatly increased by
the presence of acids.
• Invert sugar is sweeter than sucrose.
• The syrup darkens because the effect of heat
on levulose portion of the invert sugar.
• When the syrup is greatly overheated, it
becomes amber colored as the sucrose
caramelizes.
• Decomposed syrups are more susceptible to
fermentation and microbial.
• Syrups cannot be sterilized by autoclaving

Water jacketed
mixers used to
prepare syrups

DR WASFY OBEIDAT 2020

 PREPARATION OF SYRUPS
• Solution by agitation without the aid of
heat
– To avoid heat-induced inversion of
sucrose, a syrup may be prepared
without heat by agitation.
– More time-consuming than that utilizing
heat to facilitate the solution of sucrose,
but the product has maximum stability.
– Huge glass-lined or stainless steel
tanks affixed with mechanical stirrers or
agitators are employed in the large-
scale preparation of syrups.
Liquid mixer with propeller

DR WASFY OBEIDAT 2020

 PREPARATION OF SYRUPS
• Percolation method
- Percolation is the movement and filtering of fluids
through porous materials (e.g. movement of solvents
through filter paper (chromatography) (also coffee
percolation).
– In the percolation method, either sucrose is percolated to
prepare the syrup, or the source of the medicinal
component is percolated to form an extract to which
sucrose or syrup may be added.
– Ipecac syrup is prepared by adding glycerin and syrup to
an extract of powdered ipecac obtained by percolation.

DR WASFY OBEIDAT 2020

 EXAMPLE OF COMPOUNDING AND
DISPENSING SYRUP
• Potassium Gluconate Syrup 10 mEq/15 ml
– K Gluconate 56.16 g
– Orange oil 10 drops
– Na CMC 1% 20 ml
– Na Saccharin 30 mg
– Purified water q.s. 360 ml

• Compounding Procedure
– On an electronic digital balance, weigh 56.16 g of Potassium
Gluconate and put in a beaker.
– Add 168-170 ml Purified Water and stir to dissolve. With stirring,
add 20 to ml of Sodium CMC 1% solution, 30 mg of Sodium
Saccharin, and 10 drops of orange flavoring concentrate.
– Transfer the solution from the beaker into a precalibrated 360 ml or
12 oz prescription bottle (if not available, use a pint bottle), and qs
to the 360 ml mark with the water.

DR WASFY OBEIDAT 2020

– Saccharin, rather than sugar, was used in the preparation, you
may get some bitter after taste because of saccharin.

– Be sure to store this in a refrigerator, out of the reach of

children, and discard any unused portion after 14 days
(because this contains no preservative).

DR WASFY OBEIDAT 2020

 EXAMPLES OF COMMERCIALLY AVAILABLE
SYRUPs
• Albuterol Syrup (Proventil Syrup, Ventolin Syrup),
Bronchospasm
• Ipecac Syrup (Ipecac Syrup), induce vomiting
• Metoclorpromide Syrup (Reglan Syrup). Anti-vomiting
• Docusate Sodium Syrup (Colace Syrup), Stool Softener

DR WASFY OBEIDAT 2020

 ELIXIRS
• What is an elixir?
– Elixirs are clear, sweetened, hydroalcoholic solutions
intended for oral use, and are flavored to enhance their
palatability.
– Elixirs are usually less sweet and less viscous because they
contain a lower proportion of sugar. This why they are less
effective in masking the taste of medicinal substances
– The proportion of alcohol present in elixirs varies widely (5-
40%) since the individual components of the elixirs have
different water and alcohol solubility characteristics.
– Other solvents, such as glycerin and propylene glycol, are
frequently employed in elixirs as adjunct solvents.

DR WASFY OBEIDAT 2020

 PREPARATIONS OF ELIXIRS
• How elixirs are prepared?
– Alcohol-soluble and water-soluble components are generally
dissolved separately in alcohol and in purified water.

– The aqueous solution is added to the alcoholic solution,

rather than the reverse.

– When the two solutions are completely mixed, the mixture is

made to volume with the specified solvent or vehicle.

DR WASFY OBEIDAT 2020

 NONMEDICATED ELIXIRS
• What is the purpose of nonmedicated elixir?
– Nonmedicated elixirs may be useful to the pharmacist in the
extemporaneous filling of prescriptions involving:
1) The addition of a therapeutic agent to a pleasant tasting
vehicle,
2) The dilution of an existing medicated elixir

• How do we dilute medicated elixir with nonmedicated elixir?

– When a pharmacist is called on to dilute an existing medicated
elixir, the nonmedicated elixir he or she selects as the diluent
should have the approximate alcoholic concentration as the
elixir being diluted.
– The flavor and color characteristics of the diluent should not
be in conflict with the medicated elixir and all components
should be chemically and physically compatible.
DR WASFY OBEIDAT 2020
 MEDICATED ELIXIRS
• Employed for the therapeutic activity of the medicinal agent.
• Usually contain a single therapeutic agent.
• For patients taking more than a single medication, It desired
to take separate preparations of each drug.
• The advantage of having a single agent:
– The dosage of that agent can be increased or decreased
by taking more or less of the elixir without an automatic
adjustment of the other agent.

DR WASFY OBEIDAT 2020

 MEDICATED ELIXIRS
• Examples of medicated elixir
– Diphenhydramine HCl: (Benadrl Elixir), antihistamine
– Barbiturates elixir (hypnotic)
– Digoxin Elixir (Lanoxin Pediatric Elixir), heart failure, atrial
fibrillation
– Dexamethasone Elixir, (Decadron Elixir) used in the treatment
for allergies, inflammatory conditions
– Acetaminophen Elixir: (Tylenol Elixir) antipyretic and
analgesic

DR WASFY OBEIDAT 2020

Phenobarbital Elixir, USP:

Phenobarbital (therapeutic agent) 0.4% w/v

Alcohol 15% v/v
Glycerin 4.5 % v/v
Syrup (sweetener) 15% v/v
Orange oil 0.025% v/v
Color as required
Purified water ad. 100%

DR WASFY OBEIDAT 2020

 Tinctures:
• Tinctures are medicinal extracts of herbs in alcohol
• Alcohol content varies (15-80%) to protect against microbial growth
and to keeps the alcohol soluble extractives in solution.
• Other solvents such as glycerin may be employed.
• Due to high alcoholic content, some patients and physicians prefer
other forms of medication.
• Tinctures cannot be mixed successfully with liquids too diverse in
solvent character because the solute may precipitate.
• Tinctures must be stored in light resistant containers and protected
from direct sunlight.
• Examples of medicated tinctures are
– Paregoric, USP, or camphorated tincture of opium.
– Opium tincture, USP, or laudanum (more potent than
paregoric).

51
 DRY MIXTURES FOR SOLUTION
• What is dry powder for solution and what does it contain?
– Dry powder or granule form for reconstitution with a prescribed
amount of purified water immediately before dispensing to the
patient.
– A number of medicinal agents, particularly certain antibiotics,
have insufficient stability in aqueous solution to meet extended
shelf-life periods.
– The dry powder mixture contains all of the formulative
components including drug, flavorant, colorant, buffers, and
others, except the solvent.
– Once reconstituted by the pharmacist the resultant solutions
remain stable when stored in the refrigerator for the labeled
periods, usually from 7 to 14 days depending upon the
preparation

DR WASFY OBEIDAT 2020

 DRY MIXTURES FOR SOLUTION
• Examples:
• Cloxacillin Sodium for Oral
Solution (Teva) Antibioc
• Penicillin V Potassium for Oral
Solution (Pen-Vee K) Antibiotic
• Potassium Chloride for Oral
Solution (K-Lor), Potassium
supplement
• Oral rehydration solutions
• Oral Colonic Lavage Solution
• Sodium Citrate and Citric Acid
Oral Solution
Note: You should differentiate these
from suspensions
DR WASFY OBEIDAT 2020
 Oral Rehydration Solutions (ORS)
• Used to replace lost fecal water that is associated with
diarrhea which can lead to dehydration associated with
depletion of sodium, potassium and bicarbonate ions. If
sever, can result in acidosis, hyperpnea, vomiting and
hypovolemic shock and ultimately death in some
patients, particularly infants.
• ORS are effective in treatment of patients with mild
volume depletion, 5-10% of body weight.
• Solutions contain 45 mEq Na+, 20 mEq K+, 35 mEq Cl-,
30 mEq citrate, and 25 g dextrose per liter available in a
liquid or powder packet form for reconstitution with a
specific amount of water.
• These preparations should not be homemade or mixed
with or given with other electrolyte containing liquids,
such as milk or fruit juices.

DR WASFY OBEIDAT 2020

 Oral Colonic Lavage Solution
• A balanced solution of electrolytes with PEG-3350.
PEG-3350 236.00g
Sodium sulfate 22.74 g
Sodium bicarbonate 6.74 g
Sodium chloride 5.86 g
Potassium chloride 2.97 g
In 4800 ml disposable container

• Before dispensing it is reconstituted with water creating an isoosmotic

solution having a mildly salty taste (it results in no net absorption or
secretion of ions) and stored in the refrigerator (reduce the salty taste).

• Recommended dose is 4 L (240 ml quickly every 10 minutes). 1st bowel

movement occurs within 1 hr. Avoid food intake 3-4 hrs before beginning
taking the solution, except for clear liquids that are permitted after the
product is administered and prior to the examination.

DR WASFY OBEIDAT 2020

 Sodium Citrate and Citric Acid Oral Solution
• The official solution contains sodium citrate 100 mg and citric
acid 67 mg in each ml of the aqueous solution.
• Before taking, mix the dose with water. Administer orally in
doses of 10-30 ml as frequently as four times daily as an
alkalinizer.
• Used for systemic alkalinization.

DR WASFY OBEIDAT 2020

 Proper Administration and Use of liquid
Peroral Dosage Forms
• Preferably, these medications should be measured out in
calibrated devices rather than a teaspoon or tablespoon.
• Follow the administration with a glassful of water.
• Syrups that contain sucrose or another sugar are not
suitable for use in an oral prescription intended for a
diabetic patient.
• Elixirs are not suitable for use in patients who receive
concurrent medicines that possess an Antabuse-like
reactivity (Metronidazole and chlorpropamide when
mixed with alcohol the patient may get violently ill ).
• Elixirs may not be suitable for use in patients receiving
another drug that causes drowsiness.
57
NASAL PREPARATIONS

Dr. Wasfy Obeidat 1

NASAL PREPARATIONS

Dr. Wasfy Obeidat 2

Dr. Wasfy Obeidat 3
Dr. Wasfy Obeidat 4
► The nose serves to warm,
humidify and filter inhaled air.

► Nostrils are guarded by hair and

that prevents entry of dust
particles and insects.

► The floor of the nose and the roof

of the mouth are formed by hard
palatine bone and the palate.

► The soft palate that extends back

to the nasopharynx is pressed
upward and prevent lodging of
the food at the back of the nose.

Dr. Wasfy Obeidat 5

► The forward section of nasal cavity is
called vestibule.

► There are three thin elevations just behind

the vestibule and these elevated structures
are called turbinates.

► The lining of vestibule changes from skin

to squamous epithlium and then to
ciliated columnar secretory epithelium
at the turbinates.

► The olfactory region of the nose is located

toward the roof of nasal cavity and is lined
with non-ciliated neuroepithelium.
Dr. Wasfy Obeidat 6
► At the ends of nasal septum and turbinates, the nasal mucusa is
lined with ciliated epithelium.

► Mucociliary clearance is a defense mechanisms that entrap

hazardous substances within the viscoelastic mucus lining.

► The mucus is moved by claw like tips of the cilia, which is

beating in a coordinated manner with the periciliary fluid (also
called sol layer), toward the nasopharynx where the mucus or
entrapped particles is either swallowed or expectorated.

► In the nasal mucusa (also called gel layer), the frequency at

which cilia beats is 10 cm/min and clearance of bulk mucus
occurs from the nose to the nasopharynx in about 10-20
minutes.

Dr. Wasfy Obeidat 7

 FACTORS AFFECTING DRUG
ABSORPTION FROM THE NOSE
► Both physiological and ► Pharmaceutical factors
pharmaceutical factors may  Physicochemical
affect drug absorption from properties of drugs
the nose.
 Drug concentration
 Dosage form
► Physiological factors  Delivery device
 Blood supply
 Contact time
 Mucociliary clearance
 Pathological condition of
the nose
 Enzymatic activity
 Immunological clearance
 Mucus barrier
 Transport routes Dr. Wasfy Obeidat 8
 PATHOLOGICAL CONDITION OF THE
NOSE
► Excessive nasal
secretion may wash
away the nasally
administered drugs
before the drug gets
absorbed.

► Similarly, presence of
nasal polyps and
blockage can affect
nasal drug absorption
and distribution.

Dr. Wasfy Obeidat 9

 NASAL BLOOD SUPPLY
► The nasal surface is supplied with a dense network of blood
vessels from the external and internal carotid arteries.

► The nasal blood flow is very sensitive to a variety of agents

applied topically and systemically

► Changes in the ambient temperature and humidity, nasal

administration of vasoactive drugs, nasal trauma and
compression of large vein in the neck may adversely affect
blood flow in the nose.

► Fluctuation in the mood, hyperventilation and exercise can also

affect nasal blood flow.

Dr. Wasfy Obeidat 10

 ENZYMATIC ACTIVITY
► Drugs administered nasally may undergo extensive enzymatic
degradation by the enzymes present in the nose.

► In addition to P450 enzymes, oxidative phase I and conjugative

phase 2 enzymes are also present in the nasal mucosa.

► The phase I enzymes available in nasal mucosa include aldehyde

dehydrogenase, carboxyl esterase and carbonic anhydrases and
phase II enzymes are glucuronyl and sulphate transferase and
glutathione transferase.

► Drugs that have been shown to be metabolized by nasal

enzymes include progesterone, testosterone and insulin are
hydrolysed by steroid hydrolyses in rat nasal mucosa.

Dr. Wasfy Obeidat 11

► Increase in the mucociliary clearance rate decreases residence
or contact time between drug and the epithelium.

► Residence time can be increased by using bioadhesive polymers,

microspheres or by increasing the viscosity of the formulation

► Ciliated epithelium is present in the middle and posterior part of

the turbinates, but there is little or no ciliary epithelium in the
anterior regions of nasal cavity.

► For this reason, a drug deposited in the posterior part of the

nose is washed away more quickly than a drug deposited in the
anterior site of the nasal cavity.

Dr. Wasfy Obeidat 12

► The human nose can accommodate a dose of 25-200 µl per
nostril and consequently, a dose higher than this volume will be
drained off the nose.

► Formulation to the anterior part of the nose provides greater

contact between nose and drug but formulation in the posterior
portion is removed rapidly by the mucociliary clearance
mechanism of the nose.

► However, permeability of the posterior portion of the nose

is higher than that of the anterior portion.

► Slowly absorbing drug should be deposited in the anterior part

and fast absorbing drug in posterior part of the nose.

Dr. Wasfy Obeidat 13

Dr. Wasfy Obeidat 14
► Nasal solutions are mainly water based but may
contain alcohol or other solvent. They may be
available as nose drop and nose sprays.

► The presence of preservative may cause

impairment of mucociliary clearance and
subsequent irritation.

► Short residence time is another disadvantage of

nasal solutions. Nasal residence time can be
increased by adding viscosity inducing agent.

► Potent drugs that are delivered for systemic effect

may not be suitable to be administered as nose
drops.

Dr. Wasfy Obeidat 15

► Nasal suspension is not used as widely as nasal solution. Particle
size of nasal suspension should be carefully tailored to prevent
nasal irritation.

► May also contain preservatives, antioxidants and suspending

agent.

► Nasal suspension type dosage form may provide longer

residence time compared to nasal solution.

► Suspensions can also be delivered by using metered dose nasal

actuator system.

Dr. Wasfy Obeidat 16

 NASAL GEL

► Nasal gels are highly viscous

solutions or suspension. Nasal gel
formulation reduces post-nasal drip
and anterior leakage.

► One of the major disadvantages of

nasal gel would be discomfort
associated with the presence of a
semisolid in the nose.

► Vitamin B12 in a nasal gel for

systemic delivery has recently been
introduced in the US market.

Dr. Wasfy Obeidat 17

Dr. Wasfy Obeidat 18
 Humectants

► Absorption promoters

Dr. Wasfy Obeidat 19

► Nasal solutions could be administered as nasal
spray using a squeeze bottle.

► Squeeze bottles do not give reproducible dosing.

Otherwise, sprays are also available in metered
dose devices.

► Nasal sprays tend to deposit at their impaction

site in the anterior nasal cavity, where
airflow is high and mucocliliary clearance in
slow.

Dr. Wasfy Obeidat 20

 NASAL DROPS
► Nasal drops are administered by instillation
from a dropper with a flexible rubber teat or
directly from a squeezable plastic container.

► Nasal drops deposit drug throughout the

nasal cavity that offers a larger surface area
for immediate absorption.

► Some of the dose is deposited on ciliated

regions and therefore available for
immediate clearance. Some of the dose may
actually deposit at nasopharynx where it
may be swallowed.

Dr. Wasfy Obeidat 21

► After nasal administration by drops or sprays, 40% of the
administered dose is cleared within 20 minutes followed by a
second slower phase of elimination

► In the second phase of elimination clearance of the drops is

much faster than the clearance of the spray.

► Drugs administered by nasal spray bottles and inhalers only

penetrate a small portion of the nasal cavity.

► Many patients who use nasal spray bottles to administer

prescription drugs do not get the intended result or relief.

Dr. Wasfy Obeidat 22

Dr. Wasfy Obeidat 23
Dr. Wasfy Obeidat 24