INTRODUCTION:

The transdermal drug delivery systems are patches which are in the form of topically applied drugs. This drug delivery system promotes various advantages over conventional injectable and oral methods¹. The delivery of a drug across the skin layer has become a great challenge for the pharmacist and hence to overcome these problems the transdermal patches were prepared and introduced in the market, and this system of drug delivery had become very helpful for the patients. In TDDS, the drug comes in direct contact with the release liner. This is why nowadays this system is the most promising method of delivery of the drug through skin^2,3. These TDDS patches are extremely advantageous in developing the new formulations and their applications for the increase in their therapeutic activities and also reduce the first pass metabolism of the drug in the systemic circulation.

The transdermal drug delivery system promotes various advantages over conventional injectable and oral methods⁴.

In the present study, graduates have gathered the information from the available resources and compiled the article so that it can be available to them in published form. Although the subject is explored one, the intention for the publication of the present work is to seed the interest towards the publication.

BASIC COMPONENTS OF TRANSDERMAL DRUG DELIVERY SYSTEMS

1. Polymer Matrix: These polymers control the release of the drug from the drug reservoir.

Synthetic polymers: polyvinyl alcohol, polyamide, polyethylene, polypropylene, Polyurea, polymethylmethacrylate, etc^1,5.

Natural polymers: Shellac, gelatin, waxes, gums, starch, etc.

2. Drug: the drug and its component should be chosen with great care. The desirable properties of the drug for the preparation of transdermal delivery system are as follows:

· The drug should have the molecular weight approximately 1000 daltons.

· It should have an affinity for both the lipophilic and hydrophilic phase.

· It should have a low melting point.

3. Permeation Enhancers: These compounds help in accentuating skin permeability by altering the skin as a barrier to the influx of a medicament. These may be classified under the following main headings:

a) Solvents: Solvents increase the penetration by swallowing the polar pathway by fluidizing the lipids.

· Alcohols: methanol and ethanol

· Alkyl methyl sulfoxides: dimethyl sulfoxide

· Alkyl homologs of methyl sulfoxide dimethylacetamide and dimethylformamide

· Pyrrolidones: 2 pyrrolidone, N-methyl, 2-pyrrolidone, laurocapram (Azone).

· Miscellaneous solvents: propylene glycol, glycerol, silicone fluids, isopropyl palmitate.

b) Surfactants: Surfactants enhance polar pathway transport, especially of hydrophilic drugs. This property of a surfactant to alter penetration is a function of the polar head group and the hydrocarbon chain length.

· Anionic Surfactants: e.g., Dioctyl sulphosuccinate, Sodium lauryl sulfate, Decodecylmethyl sulphoxide, etc.

· Non-ionic Surfactants: e.g., Pluronic F127, Pluronic F68, etc.

· Bile Salts: e.g., Sodium ms taurocholate, Sodium deoxycholate, Sodium tauroglycocholate.

· Biliary system: These systems apparently open up the heterogeneous multilaminate pathway as well as the continuous pathways. e.g., Propylene glycol-oleic acid and 1, 4-butane diol-linoleic acid⁹.

c) Other Excipients: Some other excipients which were used here are as follows:

i. Adhesives

The fastening TDDS of the skin is done by using a pressure sensitive adhesive which can be placed either on the front face or the back side of the device and extend peripherally. Both the adhesive systems should full-fill the following criteria which are: should adhere to the skin aggressively, should be easily removed, should not leave a non-washable residue on the skin, should not irritate or sensitize the skin⁵. Ex: Silicones, Polyisobutylene¹⁰.

ii. Backing membrane

Backing membrane protects TDDS patch from the outer environment. Ex: Cellulose derivatives, Polypropylene silicon rubber (fig. 1).

Fig 1: Components of TDDS patch

FACTORS THAT ARE INFLUENCING TDDS

Biological factors include:

· Skin condition: many chemicals and solvents like chloroform, methanol, acids, and alkalis bring about damage to the skin cells and promote penetration. The fact that patients are diseased also alters the skin conditions. The better barrier would be the intact skin, but the above-mentioned conditions affect penetration.

· Skin age: Children have more sensitivity to skin absorption of toxins as young skin is more permeable than older. Hence, the skin age is one of the major factor affecting penetration of drug.

· Blood flow: Any change in peripheral circulation can majorly affect transdermal absorption.

· Skin metabolism: metabolism of some chemical carcinogens, steroids, hormones and some drugs occurs in Skin. So skin metabolism determines efficacy with which a drug shall permeate through the skin.

Applications of TDDS

•It is a safe, convenient and pain-free self-administration for the patients¹¹.

•Drugs that possess short half-life can be administered to avoid the frequent dosing administration.

•It can substitute oral administration of the medicament when the route is unsuitable as with diseases like vomiting and diarrhea. [5]

•TDDS may be terminated rapidly by removal of the application from the surface of the skin.

Pros and Cons of TDDS:

The pros of TDDS include avoiding difficulties of gastrointestinal drug absorption, avoid the first pass metabolism by it bypassing the liver, rapid termination by removal of the application from the surface of the skin, easy self-administration is possible as well as non-invasiveness. The cons include contact dermatitis at the site of application, erythema, itching, and local edema due to the use of adhesives and another excipient in the patch, drugs suitable for the transdermal patch are less because of limited drug permeation into the skin. Also, while coming in contact with water, long-time duration of adhering is difficult in transdermal patches^{12, 13, 14}.

TYPES OF TRANSDERMAL PATCHES

1. Single layer drug in adhesive: This patch has the drug in a single layer. This adhesive layer not only adheres the various layers together but also responsible for the releasing drug to the skin. A temporary liner and a backing membrane enclose the adhesive layer¹⁵(fig. 2).

Fig 2: Single layer drug in adhesive

2. Multilayer drug in adhesive: This patch contains an immediate drug release layer, and another layer will be a controlled release along with the adhesive layer wherein the adhesive layer is responsible for the releasing of the drug. This also has a temporary liner-layer and a permanent backing memberane¹⁶ (fig. 3).

Fig 3: Multilayer drug in adhesive

3. Vapour patch: In this type of TDDS patch the adhesive layer not only adhere the various layers together but also serves to release vapor mostly of essential oils¹⁷ (fig. 4).

Fig 4: Vapour Patch

4. Reservoir system: This system consists of a drug reservoir embedded between an impervious backing layer and a rate controlling membrane. The drug releases through the rate controlling membrane which is microporous or non-porous, wherein the drug is in the form of a solution, suspension, gel or dispersed in a solid polymer matrix¹⁸ (fig. 5).

Fig 5: Reservoir system

5. Drug matrix-in-adhesive: In this system inclusion of semisolid matrix is there, in which the drug solution or suspension is directly in contact with the release liner¹⁹ (fig. 6).

Fig 6: Drug matrix – in- adhesive

METHOD OF PREPARATION

1. By using “IPM membranes” method

In this method, the drug is dispersed in a mixture of water and the propylene glycol containing carbomer 940 polymers it is then stirred for 12 hrs. using a magnetic stirrer. The dispersion is then neutralized and made it viscous by the addition of triethanolamine. The7.4 pH buffer is used to improve the solubility of the poorly soluble drugs. This gel will be finally incorporated in the IPM membrane^{18, 19}.

2. “EVAC membranes” method

In this method, polyethylene (PE), 1% carbopol reservoir gel, ethylene vinyl acetate copolymer (EVAC) membranes are to be used as membranes for rate control. Propylene glycol can be used for the preparation of gel if the drug is not soluble in water. Firstly the drug is dissolved in propylene glycol then the carbopol resin is added to this solution, and the solution is made neutral by adding 5% w/w sodium hydroxide solution. The drug is now in gel form. It is then placed on a sheet of the backing layer. Over the gel, a rate controlling membrane is placed, and the edges are sealed with heat to receive a leak-proof device²⁰.

3. Aluminum backed adhesive film method

An unstable matrix is produced in case of the higher loading dose (> 10 mg). In this Case, aluminum backed adhesive film method may be a suitable one. Chloroform is choice of solvent for this method of preparation as most of the drugs as well as adhesive are soluble in chloroform. Chloroform is used to dissolve the drug, and adhesive material will be added to the drug solution and dissolved. An aluminum former that is custom-made is lined with aluminum foil and with tightly fitting cork blocks, the ends are blanked off ²¹.

EVALUATION OF TDDS

1. Interaction studies: The drugs and excipients to be used should be stable and compatible with each other.

2. The thickness of the patch: By using a digital micrometer, the thickness of the drug loaded in the patch should be measured at various points, and the average of their thickness and their standard deviation is determined for the same to ensure the thickness of the prepared patch.

3. Weight uniformity: For 4hrs, the prepared patches are to be dried at about 60 degree Celsius, cut in several parts and weighed in the digital balance and the average weight and their standard deviation value have to be determined

4. Folding endurance: A particular area of the patch is to be folded some times to give the folding endurance of the transdermal patch.

5. Percentage Moisture content: Under a desiccator containing fused calcium chloride, the films were prepared and are to be individually weighed and kept at room temperature for 24 hrs. The films should be weighed again, and the percentage of moisture content will be obtained by formula mentioned below

Percentage moisture content = [Initial weight- Final weight/ Final weight] ×100.

6. Percentage Moisture uptake: After keeping the patch for 24 hrs. In the desiccator at room temperature, containing the saturated solution of potassium chloride to maintain 84% RH, the films were to be reweighed and percentage moisture calculated using formula mentioned below

Percentage moisture uptake = [Final weight- Initial weight/ initial weight] ×100.

7. Water vapor permeability (WVP) evaluation: The water vapor permeability can be determined by foam dressing method by using a formula mentioned below

WVP=W/A

Where VWP is expressed in gm. /m2 per 24hrs,

W is the amount of vapor permeated via a patch, and it is expressed in gm. /24hrs, and

A is the surface area of the exposed sample, and it is also expressed in m².

8. Drug content: A specific area of the patch will be dissolved in a solvent of specific volume, and the solution is filtered via filter medium and analyzed the drug content with UV or HPLC technique^22,
23.

9. Uniformity of dosage unit test: An accurately weighed portion of the patch is cut into small pieces and transferred to as volumetric flask and then is further dissolved in a suitable solvent for complete extraction of the drug from the patch.

10. Shear Adhesion test: For shear adhesion test of the patch it is measured by the testing the cohesive strength of the adhesive polymer.

11. Peel Adhesion test: Peel adhesion is tested by applying force for removing the patch from the skin.

12. Flatness test: Three longitudinal strips are cut; one from the left side, and another one from the right side and checked for uniform flatness

CONCLUSION:

The transdermal drug delivery system is the novel technology for drug delivery via the skin. Due to this recent advancement in technology TDDS is now becoming the most widely accepted route of drug administration. This type of delivery system has the immense scope of being able to be used for both hydrophobic and hydrophilic API. Newer investigations to reform the cons of TDDS are required so that more and more new drug products can be introduced for transdermal delivery. The study also showed better understandings is required to optimize the mechanism of this drug delivery system. This delivery system is not only realistic but also a very practical approach to the next generation drug delivery system. With further research, this delivery system could be one of the most versatile drug delivery systems. In all, it was good to see that the students were propelled towards the said target and they have now know the basics of the publication process. Henceforth, this article will prove to be a milestone in their future research carrier.

AKNOWLEDGMENT:

The author wants to show a sincere gratitude to the Rungta College of Pharmaceutical Sciences and Research for providing necessary facilities for the completion of work.

CONFLICT OF INTEREST:

None.

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