Topical Preparation

(Topical drug delivery system)

Definition

• A topical medication is a medication that is applied to a particular

place on or in the body.
• Most often topical medication means application to body
surfaces such as the skin or mucous membrane to treat ailments via a
large range of classes including creams, foams, gels, lotions, and
ointments
• Many topical medications are epicutaneous, meaning that they are
applied directly to the skin.
• Topical medications may also be inhalational, such as asthma
medications, or
• applied to the surface of tissues other than the skin, such as eye
drops applied to the conjunctiva, or
• ear drops placed in the ear, or medications applied to the surface of
a tooth.
Advantages
There are many advantages for this drug delivery system -

• avoiding first pass metabolism which can increase its bioavailability,

• being convenient and easy to apply to a large area,

• being easy to terminate the medication and

• avoiding gastro-intestinal irritations.

All these can increase the patient compliance.

 Disadvantages
There are several disadvantages for this system -
• causing skin irritations and symptoms like rashes and itchiness may
occur.
• Also, only small particles can pass through the skin, which limits the
choice of drugs.
• Since skin is the main medium of topical drug delivery system, its
conditions determine the rate of skin penetration leading to affecting
the pharmacokinetics of the drug. The temperature, pH value and
dryness of the skin need to be considered
Depending on dermatologic applications there are 2 types of medicated
topical preparations:

1) Dermatological product:
- delivers drug into the skin in treating dermal disorders - skin is the
target organ

2) Transdermal product:
- delivers drug through the skin (percutaneous absorption) to the
general circulation for systemic effects
- skin is not the target organ
Transdermal Drug Delivery (TDD)

The drug initially penetrates through the stratum corneum and

then passes through the deeper epidermis and dermis without
drug accumulation in the dermal layer. When drug reaches the
dermal layer, it becomes available for systemic absorption via the
dermal microcirculation
Factor affecting topical drug absorption

• Topical drug absorption depends on two major factors - biological and

physicochemical properties.
• The degradation of drugs can be affected by the site of applications. Some
studies discovered different Percutaneous absorption patterns.
• Age also affects the absorption as the skin structure changes with age. The
lowered collagen and broadened blood capillary networks happen with
ageing. These features alter the effectiveness of absorption of both
hydrophilic and lipophilic substances into stratum corneum underneath the
surface of skin.
• The skin surface integrity can also affect the permeability of drugs such as the
density of hair follicles, sweat glands or disintegrated by inflammation or
dehydration.
• The other factor concerns metabolism of medications on skin. When the
percutaneous drug is applied on skin, it will be gradually absorbed down
the skin. Normally, when the drugs are absorbed, they will be metabolised
by various enzymes in our body and the amount will be lower.
• For the topical drug delivery way, degradation of drugs in skin is very low
compared to liver. The metabolism of drugs is mainly by metabolic
enzyme cytochrome P450, and this enzyme is not active in skin. The
CYP450 actively metabolized drugs can then maintain high concentration
when being applied on skin.
• The partition coefficient (K) determines the activity of topical drugs. For
transdermal activity, medicines with higher K value are harder to get rid of the
lipid layer of skin cells. The trapped molecules then cannot penetrate into the skin.
This reduces the efficacy of the transdermal drugs.
• The drugs target cells underneath the skin or need to diffuse into blood capillary to
exert their effect. Meanwhile, the size of particles affects this transdermal process.
The smaller the drug molecules, the faster the rate of penetration.
• Polarity of the drugs can affect this diffusion rate too. If the drug shows lower
degree of ionization, it is less polar. Therefore, it can have a faster absorption rate.
Ideal properties of a transdermal drug
delivery system
Dose: less than 200 mg /day
Half-life: less than 10 hours
Molecular weight: less than 400 Dalton
Melting Point: less than 20 degree C
Partition co-efficient (K): 1-4
Aqueous solubility : Less than 1mg/ml
pH (formulation): 5-9
Skin reaction: Non irritating and sensitive
Topical dosage forms:
Ointments

• Ointments are semi-solid, greasy preparations for application to the

skin, rectum or nasal mucosa.

• The base is usually anhydrous and immiscible with skin secretions.

• Ointments may be used as emollients or to apply suspended or

dissolved medicaments to the skin.
Topical dosage forms
Creams
▪ Creams are semi-solid emulsions, that is mixtures of oil and water.
▪ They are divided into two types:
A- oil-in-water (O/W) creams: which are composed of small droplets of oil dispersed in a continuous
aqueous phase.
Oil-in-water creams are more comfortable and cosmetically acceptable as they are less greasy and
more easily washed off using water.
B- water-in-oil (W/O) creams: which are composed of small droplets of water dispersed in a
continuous oily phase.
Water-in-oil creams are more difficult to handle but many drugs which are incorporated into
creams are hydrophobic and will be released more readily from a water-in-oil cream than an oil-in-
water cream.
Water-in-oil creams are also more moisturising as they provide an oily barrier which reduces water
loss from the stratum corneum, the outermost layer of the skin.
Topical dosage forms
Gels (Jellies)

• Gels are semisolid system in which a liquid phase is constrained within

a 3-D polymeric matrix (consisting of natural or synthetic gum) having a
high degree of physical or chemical cross-linking.

• They are used for medication, lubrication and some miscellaneous

applications like carrier for spermicidal agents to be used intra vaginally
Topical dosage forms

Pastes

▪ Pastes are basically ointments into which a high percentage of insoluble

solid has been added

▪ The extraordinary amount of particulate matter stiffens the system.

▪ Pastes are less penetrating and less macerating and less heating than
ointment.

▪ Pastes make particularly good protective barrier when placed on the skin.
Topical dosage forms

There are two types of pastes:

a) Fatty pastes
b) Non greasy pastes

Dusting powders
- These are free flowing very fine powders for external use.
- Not for use on open wounds unless the powders are sterilized.
Topical dosage forms

Liniments
- Liniments are fluid, semi-fluid or, occasionally, semi-solid preparations
intended for application to the skin.
- They may be alcoholic or oily solutions or emulsions.
- Most are massaged into the skin (e.g. counter-irritant).
- Liniments should not be applied to broken skin.
Topical dosage forms
Lotions
- These are fluid preparations (aqueous) for external application
without friction.

- They are either dabbed on the skin or applied on a suitable dressing

and covered with a waterproof dressing to reduce evaporation.

- Calamine lotion
Topical dosage forms
Transdermal patch

- A transdermal patch or skin patch is a medicated adhesive patch that

is placed on the skin to deliver a specific dose of medication through the
skin and into the bloodstream.

- An advantage of a transdermal drug delivery route over other types such as

oral, topical, etc is that it provides a controlled release of the medicament into
the patient.

- The first commercially available patch was scopolamine for motion sickness.
Transdermal drug delivery sytems (TDDS)

• Advantages
• Elegant alternative to injectables
• Pain and stress-free
• No need for trained specialist
• Good compliance
• Disadvantages
• Not feasible for all API !
• Well balanced lipohilicity
• High potency (high doses can not be accommodated and delivered)
• Local relations (irritation, disruption of barrier skin function)
•
• Implants
• Controlled drug delivery for over a long time (months/years)

• Principle
• Reservoir (Osmotic/diffusion) systems

• Matrix systems
• Non-biodegradable

• Biodegrable polymeric materials with dispersed drug

• Advantages – largely overcomes problems with individual compliance

• Disadvantages – mini-surgery is needed, uneasy to simply discontinue the therapy, local

reactions

• Examples: hormones/contraception