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Indian Journal of Pharmacy and Pharmacology

Indian Journal of Pharmacy and Pharmacology (IJPP) is an open-access, peer-reviewed pharmacy journal, published quarterly, as print and online by the Innovative Education and Scientific Research Foundation (IESRF) since 2014. IESRF is dedicated to the transfer of technology and research by publishing scientific journals, research content, providing professional membership, and conducting conferences, seminars, and award programs. With the aim of faster and better dissemination of knowledge, we will be publishing artic...

Transdermal drug delivery system: A review

Author Details:  Neha Choudhary * ,  Ajeet Pal Singh ,  Amar Pal Singh
DOI:  10.18231/j.ijpp.2021.002

Abstract

Transdermal Drug Delivery System is controlled medicated that is set on the skin to deliver a particular portion of medicine through the skin and into the circulatory system. It is likewise significant because of its interesting benefit such as less absorption, more uniform plasma levels, improved bioavailability, decrease side effect, efficacy and quality of the product. Transdermal dose structures may give clinicians a chance to offer more therapeutic alternatives to their patients to upgrade their consideration.

Introduction

Now a day many drugs are administered orally, but they are observed not more effective as desired so to upgrade such character TDDS was created. Drug delivery administered by the skin and attain a systemic effect of drug is called as transdermal drug delivery system.[1] These are kind of dosage form which includes drug transport to reasonable epidermis and potentially dermal tissue of the skin locally therapeutic effect.[2] While an exceptionally significant division of the drug is transported in systemic blood circulation. A transdermal dermal patch is characterized as a medicated adhesive patch which is set over the skin to deliver a particular dose of medication by the skin with a foreordained rate of release to reach into the circulation system.[3]

Advantages of transdermal drug delivery system[4], [5]

Self-medication is possible

Side effect gets reduced

Plasma drug concentration becomes maintained

Drug duration of action are extendable

GIT incompatibilities get avoided

Number of dosage frequency reduced

Easier to remember and used

Large area of application in comparison with nasal and buccal cavity

Disadvantages of transdermal drug delivery System[6], [7]

Chances to allergic reaction

High molecular drug level cannot to attain therapeutic level

It is deliver to ionic drug

It requires significant lag time

Anatomy and physiology of skin

Human skin consist of three distinct which are discuss follow as

Epidermis

The epidermis is a stratified, squamous, keratinizing epithelium. The complex layer of epidermis varies in contingent upon cell size, thickness and number of cell layers of epidermis which are going from 0.8 mm on palms and soles down to 0.06 mm on the eyelids. About 90% epidermal cells are keratinocytes or chest rated in five layers and creates keratin protein and 8% melanocytes are available. They create melanina yellow or dark colored dark shade that adds to skin shading and ingests harming UV light. A Langerhans cell emerges from red bone marrow and moves to epidermis, where they constitute little portion of epidermis cells. Markel cells are slightest several of epidermal cells.[8]

Dermis

Dermis is 3 to 5 mm thick layer and is made out of a lattice of connective tissue, which contains veins, lymph vessels and nerves. The cutaneous blood supply has basic capacity in direction of body temperature. It additionally gives supplements and oxygen to the skin while removing toxins and squander items. Vessels reach to inside 0.2 mm of skin surface and give sink conditions to most atoms entering the skin hindrance. The blood supply in this manner keeps the dermal centralization of a saturate low and the subsequent fixation contrast over the epidermis gives fundamental focus inclination to transdermal penetration.[9]

Hypodermis

The hypodermis or subcutaneous fat tissue underpins the dermis and epidermis. It fills in as a fat storage area. This layer controls temperature, gives wholesome help and mechanically security. It conveys chief veins and nerves to skin and may contain tangible weight organs. For transdermal medication conveyance, sedate needs to infiltrate through all these three layers and venture into foundational flow while if there should be an occurrence of topical medication conveyance just entrance through stratum corneum is fundamental and after that maintenance of medication in skin layers is desired.[10]

Mechanism of transdermal permeation[11], [12]

Transdermal permeation of a drug delivery system based on the

Permeation of drug by feasible epidermis

Sorption through stratum corneum

take up of the drug moiety through the capillary system in the dermal papillary layer

The rate of transdermal drug permeation, dQ/dt, through several layers of skin tissues which can be expressed as

dQ/dt =Ps(Cd - Cr)……(1)

Where

dQ/dt = Rate of skin permeation

Cd and Cr = the concentrations of skin penetrate in the donor phase (stratum corneum) and the receptor phase (systemic circulation)

Ps = overall permeability coefficient of the skin

Ps is defined as by L john

PS = KSDSS/HS……………….(2)

Where,

Ks = Partition coefficient of the penetrant

Dss = Apparent diffusivity of penetrant

Hs = Thickness of skin

At constant rate of drug permeation is achieved when Cd>Cr Then equation (1) becomes

dQ/dt = PS.CD…………………………….(3)

(dQ/dt) becomes as constant when Cd value remains genuinely constant done the span of skin permeation. To retain the Cd at a constant value, it is simple to make the drug to be released at a rate (Rr) which is regularly more prominent than the rate of skin take-up (Ra) therefore Rr>>Ra.

Thusly, the drug concentration on the skin surface (Cd) is kept up at a level which is constantly more prominent than the equilibrium (or saturation) solubility of the drug in the stratum corneum (CeS), i.e., Cd>>CeS; and a most extreme rate of skin permeation (dQ/dt)m, as written by equation.

(dQ/dt)m = PSCeS

Where (dQ/dt)m=Magnitude of Rate of skin permeation

PS = the skin permeability coefficient of drug

CeS- equilibrium solubility in the stratum corneum

Physicochemical properties of permeation[13], [14]

Partition coefficient

Lipid and Water Soluble containing drugs are positively absorbed through the skin. Intercellular route which are capable for drugs with moderate partition coefficient (logK 1 to 3) and having high lipophilicity. The transcellular route presumably prevails for more hydrophilic atoms (logK < 1).

Molecular size

Molecular size of drugs are very effective for designated as candidates for transdermal delivery which have tend to fall inside thin range of molecular weight of 100 to 500 Dalton.

Solubility/melting point-

Lipophilic molecules have a tendency to permeate through the skin quicker than more hydrophilic molecules. Drugs with high melting points have moderately low aqueous solubility at ordinary and Pressure and temperature.

Ionization

According to pH-partition theory only the unionized form of the drug can permeate by the lipid barrier in important quantities.

Physiological & pathological conditions of skin[15], [16]

Reservoir effect of horny layer

This is present in deeper layer because of irreversible binding of a part that have applied drug with the skin.

Lipid film

The lipid film on the skin surface goes about as a defensive layer to keep the expulsion of moisture from the skin and aides in keeping up the barrier function of stratum corneum.

Skin hydration

Skin hydration can be accomplished essentially by covering the skin with plastic sheeting, prompting amassing of sweat and improve the infiltration by opening the densed, closely packed cells of the skin and rises its porosity

Skin temperature

Rises in skin temperature rises the rate of skin penetration this is expected to accessibility of energy required for diffusivity.

Regional variation

Contrasts in nature and thickness of the barrier of skin cause variety in the permeability

Pathological injuries to the skin

Wounds that disturb the coherence of the stratum corneum, expands penetrability because of expanded vasodilatation caused by removal of the barrier layer

Self-metabolism

Catabolic catalysts present in the epidermis which may reduce the drug inactive over digestion or this method the topical bioavailability of the drug.

Skin barrier properties in the neonate and young infant

The pH of skin surface of new borns is higher than those in adult skin. The skin surface of the infant is marginally hydrophobic and moderately dry and harsh when looked at to that of older infants. Stratum corneum hydration stabilizesby the age of 3 months.

Skin barrier properties in aged skin

There are changes in the physiology of matured skin (>65 a long time). The corneocytes are appeared to rises in surface area which may have suggestions for stratum corneum function because of the subsequent diminished volume of intercorneocyte space per unit volume of stratum corneum.

Body site

Skin structure are differs at various places in body. Genital tissue typically gives the most permeable site to transdermal drud delivery system. The skin of the head and neck is moreover moderately porous contrasted with different locales of the body for example, the arms and legs.

Penetration enhancers

Low permeability of drugs over the skin can be enhanced by the advancement of penetration enhancers.(Patel et al,2012)
Table 1 Factors affecting permeation

Basic components of transdermal system[17]

Polymer matrix / Drug reservoir[18]

Polymers are the essential parameter of TDDS, which control the release of the drug from the gadget. Polymer matrix can be set up by dispersion of drug in solid or liquid state synthetic polymer base.

The following criteria should be satisfied for a polymer to be used in transdermal system.

Drug should be non-reactive and stable

Polymer easily available, manufactured in desired formulation

It should be constant release of drug through the life of system

Mechanical properties should not be change uncertainty big amount of drug include.

Polymers

Example

Natural Polymers:

Zein, gelatin cellulose derivatives, gums, natural rubber, shellac, waxes and chitosan etc.

Synthetic Elastomers

Hydrin rubber, Polyisobutylene, polybutadiene, silicon rubber, nitrile, Neoprene, Butyl rubber, Acrylonitrile etc.

Synthetic Polymers

Polyvinylchloride, polyethylene, polyvinyl alcohol, polypropylene, polyamide, Polyacrylate, polyuria, Polyvinylpyrrolidone, Polymethylmethacrylate etc.
Table 2 The polymers used in transdermal system

Drug

For developing a TDDS, the drug is very important part of chosen with great care. The some of the desire properties of TDDS are

Physiochemical properties

A molecular weight of drug should be less than nearly 1000 Dalton

It should have low melting Point.

It should have affinity for both hydrophilic and lipophilic phases.

Biological properties

Half-life of drug should be short.

Drug must not encourage a cutaneous allergic and irritant. response.

Daily dose of the order of a few mg/day.

Drugs should be administered for a long period of time.

Permeation enhancers

By the rises the permeability of stratum corneum in order to achieve greater therapeutic levels of the drug penetration enhancer associate with basic part of stratum corneum i.e Lipids and proteins. It is two types’ chemical and physical Permeation enhancers.[19]

Physical Permeation enhancers

Chemical Permeation enhancers

Chemical enhancers

Example

Terpenes

Carvone, menthol

Fatty acids

Lauric acid

Alcohols

Ethanol

Pyrollidones

Azone

Table 3 Classification of chemical enhancers

Physical enhancers

Techniques are instances of actual methods for improvement that have been utilized for upgrading percutaneous entrance (and absorption) of different remedial specialists.[20]

Backing laminate

Backing laminate layer are following points must be considerable-

It should be chemical resistance

It must be flexible

It is having good tensile strength

It should be non-irritant

Examples of backings laminate are polyester film and polyethylene film, polyolefin film

Release liner

It is the essential packaging material which can be secure the patch that will remove amid use of patch to the skin. It is comprised of base layer which might be non-occlusive (example paper fabric) or occlusive such as polyethylene, polyvinylchloride.

Evaluation of transdermal patches[21], [22]

Thickness

Weight uniformity

Content uniformity test

Moisture content

Tensile Strength

Drug content

Shear adhesion test

Peel adhesion test:

Thumb tack test:

Rolling ball test:

Probe tack test:

In vitro release studies

In vivo Studies

Disclosure Statement

There are no conflicts of interest.

Conclusion

TDDS used for the used for drug therapy for a less absorption, more uniform plasma levels, improved bioavailability, decrease side effect, efficacy and quality of the product. A patch has some simple components, which perform a vital role in the release of drug through the skin. Future prospective of TDDS would be focused on the controlled therapeutic use.

Source of Funding

None.

Conflict of Interest

None.

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  • DOI 10.18231/j.ijpp.2021.002
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  • Received Date March 15, 2021
  • Accepted Date March 17, 2021
  • Publication Date April 21, 2021