Principles of Topical Therapy
Moderator:- Dr. R. S. Meena
• The skin has a surface area of 1.6-2 m2
• This area enables the enhancement of
systemic treatment measures
• An extensive region for the application and
absorption of topical medications
• The active ingredients penetrate the skin
either via transepidermal or transfollicular
• Sensible topical drug therapy involves not only the selection of an
appropriate agent, but also a thoughtful consideration of the areas
of the body affected.
• Basic principles1. State of the diseased skin(Pathologic changes)
2. Age of patient
3. Area of the body
4. Concentration of the drug
5. Type of vehicle (e.g., ointment, cream, lotion)
6. Method of application
7. A defined duration of use that both maximizes efficacy and
minimizes adverse side effects.
FACTORS THAT AFFECT ABSORPTION
Therapeutic efficacy-relates to both its inherent potency and its ability
to penetrate the skin. Percutaneous absorption necessitates passage
through the stratum corneum, epidermis, papillary dermis, and into
the bloodstream. Topical medicines generally have a poor total
absorption . But it does not necessarily translate into low efficacy.
Stratum Rate-limiting barrier to percutaneous drug delivery. Composed of
Corneum ceramides, free fatty acids, and cholesterol in a 1:1:1 molar ratio and
By weight 50%, 35 % and 15% respectively. Drug penetration, will vary
depending on body site, due to its thickness. Diseased skin- Abraded
or eczematized skin presents less of a barrier.
Solvents, surfactants, and alcohols can denature the cornified layer
and increase penetration
Range from application under an airtight dressing such as vinyl gloves
or plastic wrap, to occlusion with cotton gloves or socks at night for
treatment of hands and feet, to application of a medication already
impregnated into an airtight dressing, as seen in flurandrenolide
Greatest benefit-should hydrate the skin by immersion in water.
It increased- both efficacy and side effects .
Regional Differences in Penetration in decreasing orders
5.Chest and back
6.Upper arm and legs
7.Lower arm and legs
8.Dorsa of hand and feets
9.Palmer and planter skin
Frequency of Application
• Must be specified in order to maximize the response whilst
avoiding side effects such as irritation.
• Emollients should be applied frequently enough to maintain
their physical effect.
• Active preparations are usually applied just once or twice a
• As a general rule, twice daily application of drugs such as
corticosteroids or deltanoids is only marginally more effective
than once daily application.
• Increasing the interval between applications can be a useful
method of gradually reducing the intensity of a
treatment, especially when it is difficult to do so by using a
lower concentration or less potent agent.
• The concentration is usually written as a percentage
representing the proportion of the formulation, by weight,
which is the active constituent.
• A concentration of 1% indicates that 1 g of drug will be
contained in 100 g of the formulation.
• 1% solution contains 1 g of drug in 100 ml of the formulation.
• Abbreviations w/w (weight in weight) and w/v (weight in
volume) are often employed to indicate which convention is
• Concentration of a solution is in ‘parts’; thus a 1 part in 1000
solution of potassium permanganate contains 1 g in 1 L of
solution, which could be expressed as 0.1% (w/v).
Quantity of Application
• The total quantity to be dispensed should be specified and it
is helpful to inform the patient how long the prescribed
quantity is expected to last.
• Estimates of the quantity of cream or ointment have varied.
• In one study a range of 12–27 g (average 18 g) was required
for applications by ‘trained operators’, whilst a range of 8–115
g (average 44 g) was required when the treatment was self
• In a more recent study, male patients treating themselves
applied an average of 20 g of ointment, and females applied
• Quantity required for 1 week of once-daily application to the
whole body would be approximately 140 g for males and 120
g for females.
Quantities (g) of medication required for twice daily
application to the entire body at various ages.
Daily (g) 8
Approximate quantities (g) required for each application of
Medication to different anatomical regions.
Trunk (including buttocks)
One arm and forearm
Face, neck and ears
Fingertip unit- An approximate but practical measure of
topical medication is the fingertip unit.
•This is the quantity of ointment, extruded from a tube with
a nozzle of 5 mm diameter (note that nozzles do vary
somewhat), extending from the distal crease of the
forefinger to ventral aspect of the fingertip.
•This unit weighs approximately 0.49 g in males and 0.43 g in
females and covers, on average, an area of approx 300 cm2.
The fingertip unit.
Fingertip units required for a single treatment of various
regions in children and adults adapted from. The unit is
measured using an adult finger.
Face and One upper One lower Trunk
• Generally, adherence to a treatment regimen is associated
with female gender, employment, being married, and low
• Lower adherence is seen for patients with extensive
disease, and paradoxically, Disease on the face.
• Furthermore, compliance is negatively affected by
depression, which is common in people with chronic skin
conditions and found in up to 20 percent of patients with
• Vigorous rubbing or massaging of the drug -increases the
surface area and blood supply to the area locally, augmenting
systemic absorption .
• Presence of hair follicles on a particular body site also
enhances drug delivery with the Scalp and beard areas
presenting less of a barrier when compared with the relatively
Hairless body sites.
• Skin of older individuals is poorly hydrated, with fewer hair
follicles and therefore may impede drug delivery.
• Reducing the particle size of the active ingredient increases its
surface area-volume ratio, allowing for a greater solubility of
the drug in its vehicle.
CLASSIFICATION AND CLINICAL APPLICATION
OF TOPICAL FORMULATIONS
• The vehicle is the inactive part of a topical preparation that
brings a drug into contact with the skin.
• Beneficial non-specific effectsCooling, protective, emollient, occlusive, or astringent
• Functions optimally when it is stable both chemically and
physically and does not inactivate the drug.
• It also should be nonirritating, nonallergenic, cosmetically
acceptable, and easy to use.
• Additionally, the vehicle must release the drug into the
pharmacologically important compartment of the skin.
• Finally, the patient must accept using the vehicle or else
compliance will be poor.
Used in the
and on the feet
Contain zinc oxide eg. calamine
(antiseptic and covering
properties), talc (lubricating and
drying properties), and stearate
Poultices Wet solid mass
(cataplasm of particles,
heated, that is
Used as wound
absorptive agents in
such as decubiti and
Historically, contained meal,
herbs, plants, and seeds. Modern
poultice often consists of porous
beads of dextranomer.
Protective, hydrating, Classified into five categories:
Emulsions of water-in-oil,
Emulsions of oil-in-water, and
Dermatologists commonly refer to the hydrocarbon bases and absorption bases as
ointments and the water-in-oil/oil-in-water emulsion bases as creams.
In pharmaceutical terms, all of these preparations are ointments.
Composed of a
Greasy and can
stable and do not
not used for watersoluble drugs.
silicon ointments are
composed of alternating
oxygen and silicon atoms
bonded to organic groups,
such as phenyl or methyl,
and are excellent skin
allow for the
Greasy but easier to
remove, do not contain
Eg. anhydrous lanolin and
water, with oil
and provide a
of oil, slow
the water phase
Emulsifier( or surfactant) is soluble in
both phases and surrounds the dispersed
drops to prevent their coalescence.
Preservatives are frequently added to
increase the emulsion's shelf life.
Eg. surfactants- sodium lauryl sulfate, the
quaternary ammonium Compounds,
Spans( sorbitan fatty acid esters), and
Tweens (polyoxyethyiene sorbian fatty
such as the
easily, are water
less greasy, and
the skin and
Contain a humectant (an agent that
draws moisture into the skin), such as
glycerin, propylene glycol, or
polyethylene glycol(PEG), to prevent the
cream from drying out.
oil phase may contain either cetyl or
stearyl alcohol (paraffin alcohols) to
impart a stability and velvety smooth feel
upon application to the skin.
Water- Consist either primarily Water soluble,
soluble or completely of
Depending on their
M.W., PEGs are either
liquid (eg. PEG 400) or
solid (PEG 4000).
easiiy washed off
of the skin
Made from watersoluble bases by
and/or PEGs with a
cellulose derivative or
carbopol. Newer gel
contain the humectant
glycerin, the emollient
dimethicone, or the
Clear and ease of
Easy to use on the
It will be useful in scenarios
where the practitioner desires
a high surface concentration
and low percutaneous
absorption of the drug. e.g.
topical antifungal and
They lack any protective or
If they contain high
concentrations of alcohol or
propylene glycol, they tend to
be drying or cause stinging.
Gels require preservatives.
After application the aqueous
or alcoholic component
evaporates, and the drug is
deposited in a concentrated
of powders (up to 50
%) into an ointment
such as a
hydrocarbon base or
Must be insoluble in
Stiffer than the
Commonly used are
zinc oxide, starch,
Dissolution of two or Liquid vehicle may be
more substances into aqueous,
homogenous clarity hydroalcoholic, or
(alcohol, oils, or
solutions of drugs in
oil or alcoholic
solutions of soap.
Function- localize the effect
of a drug that may be staining
or irritating (i.e. anthralin).
Impermeable barriers that
serve as protectants or
Less greasy than ointments,
more drying, and less
Aqueous solution- aluminum
acetate or Burow's solution.
Hydroalcoholic solution with
50% alcohol is called a
Base of oil or soap
Used as counterirritants,
facilitates application astringents, antipruritics,
to the skin with
emollients, and analgesics.
rubbing or massage.
Non-aqueous solution Flexible collodions have added castor oil
of pyroxylin in a
and camphor and are used, eg. to deliver
mixture with ether and 10% salicylic acid as a keratolytic agent.
applied to the skin
with a soft brush
Suspension Two-phase system
consisting of a finely
divided, insoluble drug
dispersed into a liquid
in a concentration of
up to 20%.
Eg. calamine lotion, steroid lotions, and
emollients containing urea or lactic acid
easier to apply and allow for uniform
coating of the affected area, and are often
the favorite preparation in treating
children. more drying than ointments.
Application of shake lotions effectively dries
and cools wet and weeping skin.
consist of zinc oxide, talc, calamine,
glycerol, alcohol, and water, to which
specific drugs and stabilizers may be added.
Powder is added to
Lotions to increase the
surface area of
Formulating the drug in
a solution within a pure
propellant. Propellant is
a blend of nonpolar
Used to deliver drugs formulated as
solutions, suspensions, emulsions,
powders, and semisolids. applied to
abraded or eczematized skin, aerosols lack
the irritation of other formulations.
Contains the drug within
an emulsion formulated
with a foaming agent(a
A solvent system (such
as water and ethanol),
and a propellant.
Used to deliver corticosteroids such as
betamethasone valerate and clobetasol
On application, a foam lattice forms
transiently until it is broken by both the
heat of the skin and the heat of rubbing the
foam onto the skin.
Thickening Increase the viscosity of
products or suspend
ingredients in a
Eg. beeswax and carbomers. Addition to
functioning as an ointment vehicle,
petrolatum may be added to an emulsion
to increase its viscosity. Ingredient ay have
a therapeutic effect as well as acting as part
of a vehicle.
• Non-therapeutic ingredients and include the preservatives,
antioxidants, and chelating agents.
• Preservatives protect the formulation from microbial
• The ideal preservative is effective at a low concentration
against a broad spectrum of organisms, nonsensitizing,
odor free, color free, stable, and inexpensive.
• Unfortunately, the ideal preservative does not exist.
• The parabens are the most frequent added preservatives,
and are active against molds, fungi, and yeasts, but less
effective against bacteria.
• Alternative agents include the halogenated phenols,
benzoic acid, sodium benzoate, formaldehyde, the
formaldehyde-releasing agents, and previously, thimerosal.
• Most commonly used preservatives may act as contact
• Antioxidants or preservatives prevent the drug or vehicle
from degrading via oxidation.
• Examples include butylated hydroxyanisole and burylated
hydroxytoluene, used in oils and fats.
• Ascorbic acid, sulfites, and sulfur-containing amino acids
are used in water soluble phases.
• Chelating agents, such as sodium EDTA and citric acid, work
synergistically with antioxidants by complexing heavy
metals in aqueous phases.
When do we use topical treatment?
• If a patient has a skin disorder covering <
30% of body, the topical medication
may be considered.
Choice of vehicles
• Three main determinants to choose the right
Patient’s skin type
Degree of acuity of the disease
Nature of the lesions
Choice of vehicles
• Skin type: About 50% of individuals have oily skin
• They do better with creams, lotions, or shake
lotions while the ones with dry skin do better
with ointments or pastes.
• Degree of acuity: Acute inflammatory processes
are best treted with creams or lotions.
• If the lesions are weeping, shake lotions are fine.
Hazards associated with topical
• M.C. - Localized irritant or allergic reactions.
• This can be minimized by applying treatment at the optimal
concentration and treatment intervals and by selection of the
• Sensitization is more difficult to anticipate and to prevent.
• Contact allergy can develop not only to the active
medicament but also to constituents of the vehicle.
• Almost any component may sensitize; notable examples
include ethylenediamine, propylene glycol, emulsifiers, sorbic
acid , cetyl and stearyl alcohols and fragrances.
• Patients with chronic venous eczema or leg ulcers appear to
be particularly susceptible.
Systemic Side Effects
• Absorption varies very considerably depending on the region
of skin being treated.
• Occlusion greatly enhances absorption.
• Systemic exposure can be greater than expected in children
due to their relatively high ratio of skin surface to body mass.
• In the elderly, penetration of drugs may be increased as a
result of changes in the structure of the skin.
• This effect is most pronounced in drugs which are most
• Inflammation of the skin impairs barrier function and
significantly increases drug absorption.
• This is especially significant in the erythrodermic patient
• Class I (weakest):
• Class II: Methylprednisolone
• Class III: Betamethasone 17-valerate
• Class IV (strongest): Clobetasol 17-propionate
drug put into
zinc oxide, talc
acute and subacute inflammation
and decrease friction
but no effusion
astringency, protection, cooling
Used in the intertriginous areas and
on the feet Eg. antifungals
liquid and soluble drug cooling, clear raw surface 、 acute inflammation
dissolution of two or
with lots of effusion
more substances into eg. Aqueous solutionhomogenous clarity
aluminum acetate or Burrow’s solution
powder and liquid
acute and subacute
mixture- two phase
system (conc. Up to 20%) astringency, more drying
effusion, favourite for
Eg. Calamine , steroid lotions,
emolient containing urea or lactic acid
consisting of aqueous
subacute or chronic
and oily components
O/W emulsion being readiy reduce inflammation
diluted with water,W/O
emulsion with oil Solution
Propanediol gelatin protection, lubrication subacute or chronic
of organic polymer reduce inflammation
Clear and ease of both
application and removal.
Easy to use on the
hair-bearing body sites
dosage form component
cream including protection、astringency
ointment vehicle with vaseline
strong action of
tincture resolve or steep
drug by alcohol
and aqueous solution
compound or film agent