Transdermal drug delivery system: A review
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 system4, 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 System6, 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 permeation11, 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
Table 1
Factors affecting permeation
|
Physicochemical properties of permeation13, 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 skin15, 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)
|
Basic components of transdermal system17
Polymer matrix / Drug reservoir18
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.
Table 2
The polymers used in transdermal system
|
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.
|
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
Table 3
Classification of chemical enhancers
|
Chemical enhancers
|
Example
|
|
Terpenes
|
Carvone, menthol
|
|
Fatty acids
|
Lauric acid
|
|
Alcohols
|
Ethanol
|
|
Pyrollidones
|
Azone
|
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 patches21, 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.
Conflict of Interest
None.
Acknowledgment
The authors acknowledge the chairman of Mr. Anil Chopra, Vice Chairperson Ms. Sangeeta Chopra & Pro-Chairman Mr. Prince Chopra, St. Soldier Group of Educational Society, Jalandhar for providing the necessary facilities to complete this review work.
References
S Kandavilli
V Nair
R Panchagnula
Polymers in transdermal drug delivery systemsPharm Technol20022656281
A Divya
MK Rao
K Gnanprakash
A Sowjanya
N Vidyasagar
M Gobinath
A review on current scenario of transdermal drug delivery systemInt J Res Pharm Sci201234494502
D Bhowmik
Chiranjib
M Chandira
B Jayakar
K P Sampath
Recent advances in transdermal drug delivery systemInt. J Pharm Tech Res2010216877
YW Chein
Transdermal Controlled Systemic MedicationMarcel Dekker IncNew York and Basel1987159176
D Patel
SA Chaudhary
B Parmar
N Bhura
Transdermal drug delivery system: a reviewPharm Innov201216675
RK Sharma
E Keleb
EB Mosa
AAZ Aljahwi
Transdermal drug delivery system- design and evaluationInt J Adv Pharm Sci2010120111
S Dhiman
GS Thakur
AK Rehni
Transdermal patches: a recent approach to new drug delivery systemInt J Pharm Pharm Sci2011352634
JR Robinson
VH Lee
Controlled drug delivery fundamentals and applications2nd EditionNew York200552336
R Wilson
A Waugh
A Grant
Anatomy and physiology in health and illness9th edition20013636
D Kumar
N Sharma
A C Rana
G Agarwal
ZA Bhat
A review: transdermal drug delivery system: tools for novel drug delivery systemInt. J Drug Dev Res2011337084
V Yadav
Transdermal drug delivery system: reviewInt J Pharm Sci Res20123237682
V Mathur
Y Satrawala
MS Rajput
Physical and chemical penetration enhancers in transdermal drug delivery systemAsian J Pharm20104317310.4103/0973-8398.72115
J Wiechers
Use of chemical penetration enhancers in Transdermal drug delivery-possibilities and difficultiesActa pharm19924123
SK Govil
P Tyle
Drug Delivery DevicesMarcel DekkerNew York1988388
SB Jayaswal
R Sood
Transdermal drug delivery system- A ReviewEastern Pharm1987303574750
Y Kavadya
B Behera
P Mohanty
D Routray
S Ghosh
L Das
Study of physiological and pathological skin changes in neonates: An east indian perspectiveIndian J Paediatr Dermatol20181914010.4103/ijpd.ijpd_21_17
NK Jain
SK Jain
Controlled and Novel Drug DeliveryCBS Publishers and DistributorsNew Delhi200210710
YW Chien
Novel drug delivery systems, Drugs and the Pharmaceutical SciencesMarcel DekkerNew York199279799
S Parivesh
D Sumeet
D Abhishek
Design, Evaluation, Parameters and Marketed Products of transdermal patches: A ReviewJ Pharm Res20103223540
S Mitragotri
D Blankschtein
R Langer
Transdermal drug delivery using low-frequency sonophoresisPharm Res199613341120
S Sharma
G Khurana
R Gupta
A Review on Pharmaceutical Validation and Its ImplicationsIndian J Pharm Biol Res20131031001010.30750/ijpbr.1.3.14
L John
Review on Transdermal Drug Delivery SystemInt J Pharma Res Health Sci20142426172
