Recent Advances in Transdermal Drug Delivery System (TDDS): A Review

Abstract

The transdermal route of administration has many advantages over more traditional routes of drug administration. They contain high bioavailability, lack of first-pass hepatic metabolism, stable plasma drug concns., and fact that the treatment is non-invasive. The biggest barrier to the penetration of medicinal molecules is the outer layer of the skin, stratum corneum. Thus, research to improve transdermal drug delivery (TDD) is worthwhile this layer is the area of interest. This review article is written to provide coverage commentary recent advances in TDD improvement techniques. Techniques that improve the permeability of the skin have been used developed to improve bioavailability and increase the choice of topical and transdermal drugs is a viable option. This review describes enhancement techniques based on drug/vehicle optimization, e.g selection of drugs, prodrugs and ion pairs, supersaturated drug solutions, eutectic systems, complexes, liposomes, vesicles and particles. Strengthening by changing the shell with moisturizing chemical enhancers partitioning and solubility effects affecting crustal lipid and keratin structure discussed Mechanism of action of penetration enhancers and retarders and their potential for clinical use application is described.

Introduction

I. INTRODUCTION

Drug delivery system and#40;DDSAnd#41; is a general name for a series of physicochemical technologies that can control the transport and release of pharmacologically active substances into cells, tissues and organs, so that these active substances can provide optimal effects . In other words, DDS involves administration routes and drug formulations that efficiently distribute the drug to maximize therapeutic efficacy while minimizing potential side effects (1). Depending on the route of administration, there are many different routes of administration, such as oral administration, transdermal administration, pulmonary inhalation, transmucosal administration, and intravenous injection. Among them are the transdermal drug delivery system and#40;TDDSand#41; represents an attractive approach(2). Several important advantages of transdermal medicine delivery there are limitations, enhancement of the primary metabolism of the liver maintaining remedial efficacity and stable tube medicine position The first transdermal system, TransdermSCOP, was approved by the FDA in 1979 nausea and puking associated with ravel,e.g the ocean There may be signs of percutaneous immersion of the medicine grounded on measurable medicine attention, sensible excretion of the medicine and its metabolites through urine and the case's clinical response given medicine treatment.2 Common constituents which The following are used to make TDDS(3). Transdermal medicine administration is defined as independent, separate lozenge forms that still, administer the medicine at a controlled rate through the skin if applied to complete skin. systemic rotation. Transdermal medicine delivery system and# 40; TDDSand# 41; established himself an integral part of new medicine delivery systems(4).

II. ADVANTAGES OF TDSS

1. Avoids first pass hepatic metabolism.
2. Maintains constant blood levels for longer period of time.
3. Decrease the dose of administration.
4. Decrease unwanted/ side effects.
5. Decreases gastro-intestinal side effects.
6. Easy to discontinue in case of toxic effects.
7. Increased patient compliance.
8. Great advantage for patients who are unconscious.
9. Provides an ability to modify the properties of biological barriers to improve absorption.
10. Relatively large area of application in comparison to buccal/nasal cavity.(5)

III. DISADVANTAGES OF TDDS

1. Daily dose of more than 10mg is not possible.
2. Local irritation is a major problem.
3. Drug requiring high blood levels are unsuitable.
4. Drug with long half life can not be formulated in TDDS.
5. Uncomfortable to wear.
6. May not be economical.
7. Barrier function changes from person to person and within the same person.
8. Heat, cold, sweating (perspiring) and showering prevent the patch from sticking to the surface of the skin for more than one day.
9. A new patch has to be applied daily(6).

IV. TRANSDERMAL PATCHES

A transdermal patch or skin patch is a medical tenacious a patch that's placed on the skin to deliver a specific cure medicine through the skin and into the bloodstream. It frequently promotes mending of the injured body area. Advantages of the transdermal medicine delivery route in comparison other types similar as oral, topical,etc. is that it provides a controlled release of the medicine to the case. A still, the lack of development is due to circumstance that the skin is a veritably effective hedge.

Transdermal patch may include the following components:

1. Liner - Protects the patch during storage. The liner is removed prior to use.
2. Drug - Drug solution in direct contact with release liner.
3. Adhesive - Serves to adhere the components of the patch together along with adhering the patch to the skin.
4. Membrane - Controls the release of the drug from the reservoir and multi-layer patches.
5. Backing - Protects the patch from the outer environment(7).

A. Asymmetric TPX Membrane Method

In this method, a prototype label is created using heat-sealable polyester film with a backing film. 1 cm in diameter with a concave. The concave membrane is covered by a polysymmetric membrane made of TPX bound to an asymmetric TPX membrane prepn. A dry/wet inversion is used produce an asymmetric TPX membrane. TPX is co-dissolved in cyclohexane, a solvent non-solvents to create a polymer solution.(10)

B. Circular Teflon Mold Method

They use results that contain polymers in different proportions organic detergent. The calculated quantum of drug is dissolved half the quantum of the same organic detergent. goods on different attention dissolve in the other half organic detergent and also add. Di- N- butyl phthalate is added as a plasticizer for medicinal polymer result. All contents stirred for 12 hours and also tossed around teflon form. The forms must be placed on a flat face to the face and covered with an reversed channel to check the solvent evaporation in a laminar inflow hood model at air haste m/ s. The detergent is allowed to dematerialize for 24 hours. The dried flicks must be kept for another 24 hours at 25 ±0.5 °C in a desiccator containing silica gel beforehand assessment to exclude growing goods. kidney pictures should be estimated within a week of their medication.(11)

C. Mercury Substrate Method

In this method, the drug is dissolved in a polymer solution with softener.    The above solution is stirred at a temperature of 10-15 °C minutes to form a homogeneous dispersion and pour on a flat surface of mercury covered with an inverted funnel controls solvent evaporation.(12)

D. By using IPM Membranes” Method

In this  system, the  medicine is dispersed in a admixture of water and  carbomer 940 polymer containing propylene glycol and  stirred for 12 hours on  glamorous   shifting. There must be diversification  annulled and rendered  thick by addn  triethanolamine. A buffer of pH7.4 can be used to  gain it  detergent gel if the solubility of the  medicine in waterless  result is  veritably high  bad The formed gel is added to IPM  movie(13).

E. By using Free Film Method

Free cellulose acetate film is produced by casting mercury surface. The polymer solution should be 2% by weight prepared with chloroform. Plasticizers should be with a polymer concentration of 40% (w/w). weight Five ml of the polymer solution was poured into a glass a ring that is placed on top of the mercury surface in a petri dish advice The solvent evaporation rate is regulated placing the inverted funnel on top of the Petri dish. Movie formation is detected by monitoring the mercury surface after complete evaporation of the solvent. A dry film will come separated and kept between sheets of wax paper a Dryer until use. There may be loose membranes of varying thickness is prepared by changing the volume of the polymer solution.[13].

A. Polymer Matrix or Drug Reservoir 

Reservoir Polymers are the backbone of TDDS that control drug release from the device.[17]

The following criteria should be preferred in selecting the polymer to be used in Tdds :

1. Reservoir Polymers are the backbone of TDDS that control medicine release from the device.
2. The polymer must be stable, non-reactive with the drug, easy to prepare and manufacture into the desired product, and expensive.[18].

B. Membrane

The membrane can be back- sealed to form a fund girding the medicine- containing matrix, or can be used as a single sub caste in a patch structure.

The prolixity parcels of the membrane are used to control the vacuity of the drug and/ or excipients to the skin.[19]

{Example. Ethylene vinyl acetate}

C. Drug Substances

Drug selection is the most important decision in the successful development of a transdermal product.

1. Physicochemical Properties of Drug Sub

The molecular weight of the medicine must be lower than 600 daltons.

a. Log P should be between 1- 7.

b. Melting point should be lower than 200 0C.

c. Hydrogen relating groups should be lower than 2.

d. It should have a favorable oilwater partition measure.

e. Largely acidic or alkaline medicines aren't suitable for transdermal administration.

f. Solubility in both mineral oil painting and water must be above 1 mg/ ml.[20,21]

2. Biological Properties of Drug Sub 

The diurnal systemic cure should be lower than 20 mg.

a. The half- life of the medicine must be short.

b. The drug mustn't directly irritate the skin.

c. The drug mustn't stimulate an vulnerable response in the skin.

d. Medicines suitable for transdermal administration that are broken down in the gastrointestinal tract or are inactivated in the liver during the first pass.

e. With the near- zero release profile of transdermal administration, medicine forbearance shouldn't do. • medicines that must be administered over a long period of time or that beget adverse goods on non-target up skins can also be formulated for transdermal delivery.[22,23].

D. Backing Membrane

Protects the patch from the outside world. The background layer must be impermeable to medicinal substances and permeable substances. It holds the whole system and protects the drug container from the atmosphere. Often used the basic materials are polyesters, aluminized polyethylene terephthalate and silicified polyethylene terephthalate .[24].

E. Drug Liner 

The release liner is the protective film on the TDDS patch that is removed before it is applied to the skin. It usually consists of a base layer, which can be non-occlusive (e.g. paper fabric) or occlusive (e.g. polyethylene, polyvinyl chloride) and a release layer of silicon (Aqil et al., 2006; Dimas et al., 2000.[25,26].

IX. EVALUATION PARAMETERS OF TDDS

A. Thickness of the Patch 

The thickness of the drug-filled patch is measured at various points with a digital micrometer, and its average thickness and standard deviation are determined to confirm the thickness of the finished patch.[27].

B. Weight Uniformity

Prepared patches should be dried at 60°C for 4 hours before testing. A specific patch area is cut from different parts of the site and weighed on a digital scale. Average weights and standard deviation values are calculated based on individual weights. [27].

C. Excipients

Excipients are important components of almost all dosage forms. Stability  the design depends on, among other factors compatibility of the drug with excipients. Medicine and excipients mustbe compatible to produce a product that is stable, so it is a must  identify possible physical or chemical interactions as such may affect the bioavailability and stability of the drug. If The excipients are new and have not been used in the case of active ingredient formulations compatibility studies play an important role in the formulation development Interaction studies are usually conducted  in thermal analysis, FT-IR, UV and chromatography techniques comparing their physicochemical properties such as determination, melting endotherms, characteristic wave numbers, absorption maxima, etc.[28,29].

D. Determination of Drug Control

A precisely weighted portion of the film( about 100mg) is dissolved in 100 ml of a suitable detergentwhich medicine is answerable and also a resultwas shaken continuously for 24 hours in a shaking incubator.The entire result is also sonicated. afterultrasonic treatment and posterior filtration, medicine inthe result is estimated spectrophotometrically proper dilution.[30,31].

D. Percentage Moisture Content

Weighed films are placed in a desiccator at room temperature contains a saturated potassium chloride solution to maintain 84% relative humidity (RH). Movies  then reweigh and determine the percentage of moisture absorbed.[32].

X. ADVANCED DEVELOPMENT IN TDDS

The most popular method for passive transdermal distribution is drug-in-adhesive technology; adhesives and excipients are the main subjects of formulation research. The goals of adhesive research are to decrease lag time, boost medication solubility and stability, improve skin adherence during the wear period, and accelerate the rate of distribution.[33]

XI. ACKNOWLEDGEMENT

I am very happy for the completion of this product. I would like to express my special thanks of gratitude to my guide Miss. Anjali Mali Ma’am. Who gave me the golden opportunity to do this wonderful project and have valuable guidelines and constant support with all necessary help in my work.  

I am also thankful to all my teachers and collage staff who helped me to complete this project. Secondly, I would also like to thank my parents who helped a lot by encouraging me to finish this project in a given time. And the lastly, thanks to all my friends and those who directly or indirectly helped me during this project.

Conclusion

An interesting aspect associated with transdermal drug delivery is the need to improve drug permeation across the skin. The limitations of conventional dermatotherapy are a continual driving force for the need to develop more enhanced and optimized topical and transdermal drug delivery systems. The implementation of nanotechnology for the development of advanced therapeutic tools is increasingly getting more scientific attention as it offers multiple advantages over conventional topical dermatotherapy. Although this review has demonstrated the great potential of nano-based carriers, it is important to consider prospective advancements in technology and approaches that improve targeted transdermal delivery to address some of the gaps and challenges transdermal delivery still faces.

References

[1] Woo Yeup Jeong, Mina Kwon, Hye Eun Choi & Ki Su Kim. Recent advances in transdermal drug delivery systems. [2] Woo Yeup Jeong, Mina Kwon, Hye Eun Choi & Ki Su Kim. Recent advances in transdermal drug delivery systems: a review. [3] Kumar P, Sankar C, Mishra B. Delivery of macromolecules through skin. The Indian Pharmacist 2004,5(3): 7-17. [4] Chien, YW, Novel drug delivery systems, Drugs and the Pharmaceutical Sciences, Vol.50, Marcel Dekker, New York, NY;1992;797. [5] google.com/search?q=advantages+and+disadvantages+TDDS&sca_esv=575127353&tbm=isch&source=lnms&sa=X&ved=2ahUKEwiT4YeHm4SCAxXqamwGHeYPBOsQ_AUoAXoECAIQAw&biw=1280&bih=683&dpr=1#imgrc=GjqN7d206myhDM. [6] https://www.google.com/search?q=advantages+and+disadvantages+TDDS&sca_esv=575127353&tbm=isch&source=lnms&sa=X&ved=2ahUKEwiT4YeHm4SCAxXqamwGHeYPBOsQ_AUoAXoECAIQAw&biw=1280&bih=683&dpr=1#imgrc=rV3re83FM_e5FM. [7] Valenta, C. and Almasi-Szabo, I. (1995). In vitro diffusion studies of ketoprofen transdermal therapeutic system. Drug Dev.Ind. Pharm, 21:1799-1805. [8] Punasiya R, Joshi A, Gupta S, Punasiya J. Transfersomes- A Novel Carrier for Transdermal Drug Delivery. Research J. Pharma. Dosage Forms and Tech. 2010; 2(2):133-138. [9] Shrivastava D. Transdermal Approach of Antidiabetic Drug Glibenclamide: A Review. W J Pharm Pharma Sci 2012; 1:532-544. [10] Zhang H, Zhang J, Streisand JB. Oral mucosal drug delivery: clinical pharmacokinetics and therapeutic applications. Clin Pharmacokinet. 2002;41(9):661-80. [11] Wiechers J. Use of chemical penetration enhancers in Transdermal drug delivery-possibilities and difficulties. Acta pharm. 1992 : 4: 123. [12] Yamamoto T, Katakabe k, Akiyoshi K, Kan K and Asano T. Topical application of glibenclamide lowers blood glucose levels in rats. Diabetes res. Clin. Pract. 1990; 8: 19-22. [13] Crawford R.R and Esmerian O.K. Effect of plasticizers on some physical properties of cellulose acetate phthalate films. J. Pharm. Sci. 1997;60: 312-314. [14] Balakrishnan P, Shanmugam S, Lee WS, Lee WM, Kim JO, Oh DH, et al. Formulation and in vitro assessment of minoxidil niosomes for enhanced skin delivery. Int J Pharm. 2009 Sep;377(1-2):1-8. [15] Jain.N.K, Controlled and novel drug delivery, first edition, CBS publishers and distributors, New Delhi.1997. [16] Mathiowitz.Z. E, Chickering, Lehr.C.M, Bio adhesive drug delivery systems; fundamentals, novel approaches and development, Marcel Dekker, Inc. New York. Basel. [17] Arunachalam A, Karthikeyan M, Kumar DV, Prathap M, Sethuram S, Kumar AS. Transdermal drug delivery system: A review. Curr Pharma Res 2010;1:70-81. [18] Sugibayashi K, Morimoto Y. Polymers for transdermal drug delivery systems. J Control Release 1994;29:177-85. [19] Patel RP, Baria AH. Formulation and evaluation consideration of transdermal drug delivery system. Int J Pharm Res 2011;3:1-9. [20] Finnin, B.C. and Morgan, T.M. Transdermal penetration enhancers: applications, limitations and potential, J. Pharm. Sci. 1999; 88(10): 955. [21] Guy, R.H., Hadgraft, J. and Bucks. D.A.W. Xenobiotica. 1987; 17: 325.For physicochemical properties. [22] Flynn, G.L. and Stewart, B. Percutaneous drug penetration: choosing candidates for transdermal development. Drug Dev. Res. 1988; 13: 169-185. [23] Guy, R.H., Hadgraft, J. and Bucks. D.A.W. Xenobiotica. 1987; 17: 325. For biological properties. [24] Chad RW. Development and Selection of Components for Transdermal Drug Delivery Systems, [ Internate]. [25] Aqil, M., Ali, A., Sultana, Y., Dubey, K., Najmi, A. K., Pil-lai, K.K., 2006. In vivo characterization of monolithic matrix type transdermal drug delivery systems of pi-nacidil monohydrate: A technical note. AAPS Pharm Sci Tech, 7(1), Article 6. [26] Dimas DA, Dallas PP, Rekkas DM, Choulis NH. Effect of several factors on the mechanical properties of pres-sure- sensitive adhesives used in transdermal thera-peutic systems. AAPS PharmSciTech. 2000; 1(2): Ar-ticle 16. [27] Aarti N, Louk A.R.M.P, Russsel.O.P and Richard H.G.Mechanism of oleic acid induced skin permeationenhancementin vivoin humans. Jour. control. Release 1995;37: 299-306. [28] Yan-yu X, Yun- mei S, Zhi-Peng C and Qi-nerg P. Preparation of silymarin proliposomes; A new way to increase oral bioavailability of silymarin in beagle dogs. Int. pharm. 2006; 319: 162-168. [29] Wade A, Weller P.J. Handbook of pharmaceutical Excipients. Washington, DC: American Pharmaceutical Publishing Association; 1994: 362-366 [30] Patel D, Chaudhary SA, Parmar B, Bhura N. Transdermal drug delivery system: a review. The Pharm Innovation. 2012;1(4):66-75. [31] Sharma A, Saini S, Rana AC. Transdermal drug delivery system: A review. Int. J Res Pharm Biomedical Sci.2013;4(1):(286-292). [32] Dipali A. Chavan*, Pravin B. Suruse, Lokesh G. BardeRECENT ADVANCES IN TRANSDERMAL DRUG DELIVERY SYSTEM (TDDS). [33] Lee WR, Shen SC, Wang KH, Hu CH, Fang JY. The human skin barrier is organized as stacked bilayers of fully extended ceramides with cholesterol molecules associated with the ceramide sphingoid moiety. J Invest Dermatol. 2012 Aug;132(8):2215-25.

Copyright

Copyright © 2023 Mr. Shrikant Raju Wadekar, Miss. Anjali Mali, Dr. Gajanan Sanap. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.