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Review Article
Keywords: Gelling agents, pecutaneous penetration of drug, penetration enhancers, transdermal drug
delivery, transdermal gel
Received 20 August 2015 Received in revised form 8 Sept 2015 Accepted 10 Sept 2015
Advantages of transdermal gels [8, 9] because of the natural limits of drugs entry
1. Avoids the first pass hepatic metabolism imposed by skins impermeability.
2. Drug delivery can be easily eliminated in Many drugs with a hydrophilic structure
case of toxicity. permeate the skin too slowly are of less
3. Fewer side effects as there is reduced therapeutic effect.
plasma concentrations of drugs. Desirable properties of gels:
4. Dosing frequency get reduced which It should be inert, compatible with other
increases the patient compliance. additives and non-toxic.
5. Through transdermal gels drug is It should be stable at storage condition.
delivered in a steady rate over an extended It should be free from microbial
period of time. contamination.
6. Conventional dosage forms follow a peak It should maintain all rheological
and valley pattern of drug release kinetics properties of gel.
in blood and tissue. Transdermal drug It should be washable with water and free
delivery system is designed to release from staining nature.
drugs at a predetermined rate and It should not affect biological nature of
continuously avoiding unnecessarily high drug.
peaks and sub therapeutic troughs in It should be convenient in handling and its
plasma drug levels. application.
7. Increases the therapeutic value of many It should possess properties such as
drugs as it avoids the problems associated
thixotropic, greaseless, emollient, non-
with drugs e.g. GI irritation, nausea, staining etc.
vomiting, heartburn and increased
Classification of gels [10]
appetite after oral therapy. 1. On the basis of phase system:
8. Provides ease of rapid identification of
Two phase system: The gel may consist of
medication in emergencies, non-
floccules of small molecules rather than
responsive patients, unconscious or
large molecules. The gel structure is not
comatose patients.
always stable in these systems. These gels
9. Equivalent therapeutic effect with lower
may be thixotropic, semi-solid on standing
dose of drug can be achieved than is
and become liquid on agitation.
necessary when drug is given orally.
Single phase system.
10. Drugs that are degraded by enzymes and
2. On the basis of chemical nature:
acids in the gastrointestinal system can
be administrated by incorporating in Inorganic gel
transdermal gels. Organic gel
11. Continuity of drug administration 3. On the basis of structure:
permitting the use of a drug with short Physical gels: unstable at high temperature
biological half-life. or in solvents.
Limitations of transdermal gels Chemical gels: not tough due to uneven
Transdermal gels are unsuitable for drugs temperature.
that irritate or sensitize the skin. Slide ring gels: in that polymer chains are
Transdermal gels are not suitable for covalently cross did not link nor
drugs which have very low or high attractively interacted rather they are
partition coefficient. Drug should have interlocked.
favourable partition coefficient (logP 1-3). ORGANOGELS [11]
For heavy drug molecules (>500Da) it Organogel, a viscoelastic system, is a semi-
becomes to penetrate the stratum cornea. solid preparation which has an immobilized
external apolar phase. Organogels are
Transdermal gels are not favorable for
thermodynamically stable in nature and
drugs which are extensively metabolized
regarded as matrices for the delivery of
in skin.
bioactive agents. The thermodynamic
Only relatively potent drugs are suitable
behavior of the organogels results in the
candidates for transdermal delivery
formation of fibrous structure because of
a) Whether the drug molecules are dissolved used. Some of the desirable properties of
or suspended in the delivery system. penetration enhancers are:
b) The interfacial partition coefficient of the They should be non toxic, non irritating
drug from the delivery system to skin. and non allergic.
c) pH of the vehicle. The activity and duration of action of
2. Enhancement of transdermal permeation: penetration enhancers should be
Majority of drugs will not penetrate the predictable and reproducible.
skin at rates sufficiently high for They should not have any
therapeutic efficacy. The permeation can pharmacological action in the body.
be improved by the addition of The penetration enhancers should work
permeation enhancer into the system. unidirectional i.e. should allow therapeutic
III. Physiochemical and pathological agents into the body whilst preventing the
conditions of skin: loss of endogeneous material from the
1. Reservoir effect of horny layer: The horny body.
layer especially is deeper layer can The penetration enhancers should be
sometimes act as a depot and modify the compatible with drugs and excipients.
transdermal permeation of drugs. This Types of penetration enhancers
effect is due to irreversible binding of a 1. Chemical penetration enhancers
part of the applied drug with the skin. 2. Physical penetration enhancers
2. Lipid film: The lipid film on the skin Chemical penetration enhancers:
surface acts as a protective layer to Chemical penetration enhancers involves the
prevent the removal of moisture from the use of chemicals to allow the entry of poorly
skin and helps in maintaining the barrier penetrating molecules to across the skin
function of stratum corneum. barrier. Substances reported to render the
3. Skin hydration: Hydration of stratum stratum corneum more permeable include
corneum can enhance permeability. Skin alcohols, polyalcohols, pyrrolidones, amines,
hydration can be achieved simply by amides, fatty acids, sulphoxides, esters,
covering or occluding the skin with plastic terpenes, alkanes, surfactants and
sheeting, leading to accumulation of sweat. phospholipids.
Increased hydration appears to open up Physical penetration enhancers: In this
the dense closely packed cells of the skin physical and electrical methods are used as
and increases its porosity. penetration enhancers. This includes the
4. Regional variation: Differences in nature iontophoresis, phonophoresis,
and thickness of the barrier layer of skin electroporation and photomechanical waves.
causes variation in permeability. Mechanism of action of penetration
5. Pathological injuries to the skin: Injuries enhancers [27]
that disrupt the continuity of the SC There are so many ways by which
increases permeability due to increased penetration enhancers increases the
vasodialtion caused by removal of the penetration of drug. They can act by their
barrier layer. direct action on skin or by modifying the
6. Skin temperature: Raising the skin formulation. Mechanism of action of
temperature results in an increase in the penetration enhancers which directly act on
rate of skin permeation; this may be due to skin are:
availability of thermal energy required for i. They directly act on stratum corneum
diffusivity. intercellular keratin, denature it or modify
7. Cutaneous self-metabolism: Catabolic their confirmation by causing swelling and
enzymes present in the epidermis may by increasing hydration.
render the drug inactive by metabolism ii. They act on desmosomes which maintain
and the topical bioavailability of the drug the cohesion between corneocytes.
is gently reduced. iii. They cause the disruption of the lipid
PENETRATION ENHANCEMENT [26] bilayer and the enhancer gets
To increase the penetration of drug across heterogeneously concentrated within the
stratum corneum, penetration enhancers are domains of bilayer lipids.
iv. They alter the solvent nature of the 10. Gupta S, Singh Ravindra P, et al. Organogel. A
stratum corneum to modify partitioning of viable alternative for existing carrier system.
IJCP, 2004, 1-4.
the drug or of a cosolvent into the tissue.
11. Sahoo S, Kumar N, Bhattacharya C, Sagiri SS, Jain
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