topical therapy, factors that affect absorption, frequency of applicatoin, preparations, creams, ointments, lotions, gels

1. Seminar presentation
Principles of Topical Therapy
Moderator:- Dr. R. S. Meena

2. • 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
pathways

3. • 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.

4. FACTORS THAT AFFECT ABSORPTION
CUTANE
OUS
DRUG
DELIVERY
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
Occlusio
n
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
(Cordran) tape.
Greatest benefit-should hydrate the skin by immersion in water.
It increased- both efficacy and side effects .

5. •
•
•
•
•
•
•
•
•
•
•
Regional Differences in Penetration in decreasing orders
1.Mucous membrane
2. Scrotum
3. Eyelids
4. Face
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
10.Nails

6. 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
day.
• 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.

7. Drug concentration
• 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
being used.
• 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).

8. 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
administered.
• In a more recent study, male patients treating themselves
applied an average of 20 g of ointment, and females applied
17 g.
• 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.

9. Quantities (g) of medication required for twice daily
application to the entire body at various ages.
Age
Requirement
Daily (g) 8
Weekly (g)
3 months
8
56
6months
10
67
12 months
12
84
18 months
13
93
2 years
14
95
3 years
16
112
4 years
19
135
5 years
20
140
7 years
25
172
10 years
30
210
12 years
37
256

10. Approximate quantities (g) required for each application of
Medication to different anatomical regions.
Anatomical region
Males
Females
Trunk (including buttocks)
6.6
5.8
One leg
2.9
2.5
One foot
0.9
0.7
One arm and forearm
1.7
1.3
One hand
0.6
0.5
Face, neck and ears
1.3
0.9
Whole body
20
17

11. 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.
fingertip unit
•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.

12. Fingertip units required for a single treatment of various
regions in children and adults adapted from. The unit is
measured using an adult finger.
Age
Face and One upper One lower Trunk
neck
limb
limb
Whole body
3–6 month
1
1
1.5
2.5
8.5
1–2 years
1.5
1.5
2
5
13.5
3–5 years
1.5
2
3
6.5
18
6–10 years
2
2.5
4.5
8.5
24.5
Adult
2.5
4.5
7.6
13.5
40

13. Compliance
• Generally, adherence to a treatment regimen is associated
with female gender, employment, being married, and low
prescription costs.
• 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
psoriasis.

14. Miscellaneous Factors
• 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.

15. 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
properties.
• 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.

16. Frequently employed constituents of vehicles
Lipids
Castor oil, Cetyl alcohol, Cocoa butter, Isopropyl myristate,
Isopropyl palmitate, Lanolin, Liquid paraffin, Shea butter, Stearic acid,
Stearyl alcohol, White soft paraffin (petrolatum)
Emulsifiers
Alkyl sulphates and sulphonates, Glyceryl monostearate, Lanolin and
derivatives, Phosphoric acid esters, Polyethylene glycols, Polyvalent
metallic soaps, Propylene glycol fatty acid esters, Quaternary
ammonium cationic compounds, Sorbitan monolaurate,
monopalmitate and mono-oleate, Triethanolamine oleate
Humectants
Gelatine, Glycerin, Propylene glycol, Pyrrolidone carboxylic acid,
Sorbitol, Urea
Penetration
enhancers
Azone, Dimethyl sulphoxide, Propylene glycol, Salicylic acid, Urea
Preservative
s
Benzyl alcohol, Butylated hydroxyanisole, Butylated hydroxytoluene
Chlorocresol, Edetic acid/disodium edetate, Hydroxybenzoates
(parabens), Propylene glycol, Sodium metabisulphite, Sorbic
acid/sorbates
Solvents
Acetone, Ethanol, Ether, Chloroform, Glycerin, Isopropyl alcohol
Methanol, Propylene glycol, Water

17. Powders
Absorb
moisture and
decrease
friction
Used in the
intertriginous areas
and on the feet
Eg. antifungals
Contain zinc oxide eg. calamine
(antiseptic and covering
properties), talc (lubricating and
drying properties), and stearate
(improved adherence)
Poultices Wet solid mass
(cataplasm of particles,
)
sometimes
heated, that is
applied to
diseased skin
Used as wound
cleansers and
absorptive agents in
exudative lesions
such as decubiti and
leg ulcers.
Historically, contained meal,
herbs, plants, and seeds. Modern
poultice often consists of porous
beads of dextranomer.
Ointments Semisolid
preparations
that spread
easily.
Protective, hydrating, Classified into five categories:
and lubricating.
Hydrocarbon bases,
Absorption bases,
Emulsions of water-in-oil,
Emulsions of oil-in-water, and
Water-soluble bases.
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.

18. HYDR0CARB0N
BASES
(oleaginous
bases)
Composed of a
mixture of
hydrocarbons of
varying
molecular
weights, m.c.
petrolatum
Greasy and can
stain clothing.
stable and do not
contain
preservatives.
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
protectants.
ABSORPTI0N
BASES
Contain
hydrophilic
substances that
allow for the
absorption of
water-soluble
drugs.
Lubricating and
hydrophilic, can
form emulsions.
Function as
emollients and
protectants
Greasy but easier to
remove, do not contain
water.
Eg. anhydrous lanolin and
hydrophilic petrolatum.

19. CREAMS(
WATERIN-0IL
EMULSIO
N)
By definition,
contains <25%
water, with oil
being the
dispersion
medium.
two-phase
systems may
separate
unless shaken
Less greasy,
spread easily,
and provide a
protective film
of oil, slow
evaporation of
the water phase
provides a
cooling effect
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
acid esters).
Oil-inwater
Emulsion
s
Contains >31
% water.
Contain
preservatives,
such as the
parabens, to
inhibit the
growth of
molds.
Spread very
easily, are water
washable and
less greasy, and
are easily
removed from
the skin and
clothing.
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.

20. Water- Consist either primarily Water soluble,
require no
soluble or completely of
various PEGs.
preservative
bases
Depending on their
M.W., PEGs are either
liquid (eg. PEG 400) or
solid (PEG 4000).
Gels
additives.
nonstaining,
greaseless, and
easiiy washed off
of the skin
Made from watersoluble bases by
formulating water,
propylene glycol,
and/or PEGs with a
cellulose derivative or
carbopol. Newer gel
contain the humectant
glycerin, the emollient
dimethicone, or the
viscoelastic
polysaccharide
hyaluronic acid
Clear and ease of
both application
and removal.
Easy to use on the
hair-bearing body
sites
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
antibiotics (mupirocin).
They lack any protective or
emollient properties.
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
form.

21. Pastes
High concentrations
of powders (up to 50
%) into an ointment
such as a
hydrocarbon base or
a water-in-oil
emulsion
Must be insoluble in
the ointment.
Stiffer than the
original ointment.
Commonly used are
zinc oxide, starch,
calcium carbonate,
and talc.
Solution
Dissolution of two or Liquid vehicle may be
more substances into aqueous,
homogenous clarity hydroalcoholic, or
non-aqueous
(alcohol, oils, or
propylene glycol).
Liniment
s
Non-aqueous
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
sunblocks.
Less greasy than ointments,
more drying, and less
occlusive.
Aqueous solution- aluminum
acetate or Burow's solution.
Hydroalcoholic solution with
50% alcohol is called a
tincture.
Base of oil or soap
Used as counterirritants,
facilitates application astringents, antipruritics,
to the skin with
emollients, and analgesics.
rubbing or massage.

22. Coliodion
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.
ethanol
applied to the skin
with a soft brush
Suspension Two-phase system
or Lotion
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.
Shake
lotions
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
evaporation

23. Aerosols
Formulating the drug in
a solution within a pure
propellant. Propellant is
a blend of nonpolar
hydrocarbons.
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.
Aerosol
foams
Contains the drug within
an emulsion formulated
with a foaming agent(a
surfactant),
A solvent system (such
as water and ethanol),
and a propellant.
Used to deliver corticosteroids such as
betamethasone valerate and clobetasol
propionate.
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
agents
products or suspend
ingredients in a
formulation
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.

25. Stabilizers
• Non-therapeutic ingredients and include the preservatives,
antioxidants, and chelating agents.
• Preservatives protect the formulation from microbial
growth.
• 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.

26. • 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
sensitizers.

27. • 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.

28. When do we use topical treatment?
• If a patient has a skin disorder covering <
30% of body, the topical medication
may be considered.

29. Choice of vehicles
• Three main determinants to choose the right
vehicle are:
Patient’s skin type
Degree of acuity of the disease
Nature of the lesions

30. Choice of vehicles
• Skin type: About 50% of individuals have oily skin
or seborrhea.
• 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.

31. Choice of vehicles for different lesions

32. Topical agents Ⅰ
Classification
Action
Smooth agents
reduce friction
avoid stimulation
Antimycotics
Antiseptics
Drug
Concentration(%)
calamine
talc
zinc oxide
kill or inhibition
sulphur
Glacial Acetic Acid
benzonic acid
salicylic acid
clotrimazole
Miconazole
Terbinafine
kill or inhibition
boracic acid
potassium
permanganate
Neomycin
revanol
10-15
10-70
20-50
5—10
5--30
6--12
5--10
2---3
2
1
3---4
1/2000
1/5000
0.5-1
0.1

33. Topical agents Ⅱ
Classification
Antipruritics
Action
narcotism、
dimimish inflammation
stop itchness
Drug
Concentration(%)
cool
mint
carbolic acid
bendazolecain
dexamethasone
triamcinolone
Keratoplastics promote normal keratosis
pityrol
shrink blood vessel
coal tar
reduce effusion and
resorcinol
inflammatory infiltration
salicylic acid
1---5
0.2-3
1---2
3---5
0.025
0.025
3---5
5--40
2---5
3

34. Topical agents Ⅲ
Classification
Action
Concentration(%)
keratolytics
Drug
hyperkeratosis
salicylic acid
make keratinocytes loose resorcinol
separate and fall off
Glacial Acetic Acid
urea
Caustics
remove granulation
carbolic acid
tissue and neoplasm
Glacial Acetic Acid
salicylic acid
trichloroaceticacid
sunscreen absorb or prevent
Titanium dioxide
ultraviolet radiation
depigmenting reduce pigmentation
Hydroquinone
agents
Azelaic Acid
6--15
6--15
10-30
20-40
pure
>30
>20
>30
5
3
20

35. Topical corticosteroids
Potency
Ultra high
Class
Formulation
II
Clobetasol propionate
Cream, 0.05%
Diflorasone diacetate
High
I
Topical corticosteroid
Ointment, 0.05%
Amcinonide
Ointment, 0.1%
Betamethasone dipropionate Ointment, 0.05%
Desoximetasone
Fluocinonide
Cream, ointment or gel,
0.05%
Halcinonide
III
Cream or ointment, 0.025%
Cream, 0.1%
Betamethasone dipropionate Cream, 0.05%
Betamethasone valerate
Ointment, 0.1%
Diflorasone diacetate
Cream, 0.05%
Triamcinolone acetonide
Ointment, 0.1%

36. Moderate
IV
Ointment, 0.2%
Triamcinolone acetonide
Cream, 0.1%
Betamethasone dipropionate
Lotion, 0.02%
Betamethasone valerate
Cream, 0.1%
Fluocinolone acetonide
Cream, 0.025%
Fludroxycortide
Cream, 0.05%
Hydrocortisone butyrate
Cream, 0.1%
Hydrocortisone valerate
Cream, 0.2%
Betamethasone valerate
Lotion, 0.05%
Desonide
Cream, 0.05%
Fluocinolone acetonide
VII
Ointment, 0.05%
Hydrocortisone valerate
VI
Ointment, 0.025%
Fludroxycortide
Low
Cream, 0.05%
Fluocinolone acetonide
V
Desoximetasone
Solution, 0.01%
Dexamethasone sodium phosphate Cream, 0.1%
Hydrocortisone acetate
Cream, 1%
Methylprednisolone acetate
Cream, 0.25%

38. Side effects of topical corticosteroids
•
•
•
•
•
Epidermis : Atrophy
Hair follicles: Steroid acne
Dermis: Atrophy, striae
Pigmentation: Hypopigmentation
Vessels: Erythema, telangiectases

39. Hazards associated with topical
treatment
• 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
correct vehicle.
• 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.

40. Systemic Side Effects
• Rare
• 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
hydrophilic .
• Inflammation of the skin impairs barrier function and
significantly increases drug absorption.
• This is especially significant in the erythrodermic patient

41. •Thanks

42. Topical agents
•
•
•
•
•
•
•
•
•
Keratolytic agents
Cytotatic agents: Podophyllin, 5-fluorouracil
Retinoids
Antibiotics, antifungals, antiviral agents
Corticosteroids
Combination products
Tacrolimus, pimecrolimus
Nonsteroidal antiinflammatory agents
Sunscreens

43. • Class I (weakest):
Hydrocortisone, prednisolone
• Class II: Methylprednisolone
aceponate, triamcinolone
• Class III: Betamethasone 17-valerate
• Class IV (strongest): Clobetasol 17-propionate

44. Formulation Ⅰ
Dosage form
Powder
Solution
Lotion
Cream
component
action
indications
drug put into
zinc oxide, talc
and stearate
Absorb moisture
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
reduce inflammation
with lots of effusion
more substances into eg. Aqueous solutionhomogenous clarity
aluminum acetate or Burrow’s solution
powder and liquid
protection, cooling
acute and subacute
mixture- two phase
reduce inflammation
inflammation without
system (conc. Up to 20%) astringency, more drying
effusion, favourite for
Eg. Calamine , steroid lotions,
children
emolient containing urea or lactic acid
consisting of aqueous
protection、lubrication
subacute or chronic
and oily components
intenerate crust
inflammation ,pruritus
O/W emulsion being readiy reduce inflammation
diluted with water,W/O
emulsion with oil Solution

45. Formulation Ⅰ
Dosage form
Gel
•
component
action
indications
Propanediol gelatin protection, lubrication subacute or chronic
of organic polymer reduce inflammation
inflammation ,pruritus
drug
Clear and ease of both
application and removal.
Easy to use on the
hair-bearing body sites

46. Fomulation Ⅱ
action
dosage form component
Paste
indications
cream including protection、astringency
25%-50% powder
intenerate crust
diminish inflammation
ointment vehicle with vaseline
or lanolin
strong action of
lubrication、penetration
intenerate crust
tincture resolve or steep
diminish inflammation
drug by alcohol
antipruritic
subacute inflammation,
scar,erosion
chronic inflammation
ulcer
chronic inflammation
sterilization
pruritus

47. Fomulation Ⅱ
dosage form
Plastics
component
action
organic menstruum
and aqueous solution
contain macromolecule
compound or film agent
indications
protection
strong percutaneous
strong percutaneous
action
chronic
inflammation