INTRODUCTION:

Transdermal drug delivery systems (TDDS) allow drugs to be absorbed through the skin. There is no need to administer intravenous or oral medications to systemic or local organs. As a result, the drugs are delivered at a controlled ratio, which reduces the burden of intravenous administration and the loss caused by the first-pass effect of the liver. The stratum corneum and epidermal layer must be broken to develop formulations of TDDS1.

Besides preventing thrombosed entrance into the systemic circulation, TDDS also allows controlled and continuous administration of drugs with short biological half-lives. Motion sickness, nausea, and vomiting have been treated with TDDS since 1981. As a system for systemic drug administration, the transdermal patch has been approved as a form of delivery where no visible amounts of the drug can penetrate the skin.

Drugs were previously only administered trans dermally through passive patches that were dependent on their diffusion through the skin. Agents that are delivered across a barrier enable, in some ways, an extensive range of properties, including compounds with extremely challenging physical properties. In response, active patches for pain management, protein delivery, and immunization were developed. These patches are generally smaller and adhere better. TDDS is becoming an integral part of a novel drug delivery system. TDDS is defined as the application of self-controlled, distinct dosage forms to intact skin to deliver drugs at a controlled rate into the system. These include TDDSs that increase the rate of drug absorption, the rate of drug absorption, and ultimately the bioavailability of the drug. A TDDS delivers the drug trans dermally.

Components of Tdds:

The main components of TDDS are³:

Drug: The drug should be in the form of a solution, and it must be potent.

Liner: The patch is protected during storage. The liner has to be removed before using the patch.

Adhesive: The adhesive serves both to adhere the patch to the skin and to adhere the constituents of the patch together.

Rate controlling membrane: The reservoir adjusts the release of the drug

Backing layer: The patch is protected from the outside environment.

Permeation Enhancers: These are infusion promoters for drugs, which increase the entry of the drug into the blood

Matrix Fillers: Bulk to the matrix, and some act as matrix stiffening agents.

Other components: stabilizers, preservatives, etc.,

TYPES OF TDDS

TDDS patches are of the following types⁴:

Single-layer Drug-in-Adhesive:

The drug is also contained in the adhesive layer. The adhesive layer serves as both a binding agent and a mechanism to release the medication from the patch, as well as adhere the various layers of the patch together. It comes with a temporary liner and a backing that surround the adhesive layer.

Multi-layer Drug-in-Adhesive:

A multi-layer patch is an addition to a single-layer patch, adding layer of drug-in-adhesive between two membranes (but not always). In the first layer, the drug is released immediately, and in the second layer, it is released in a controlled manner. In addition to the permanent backing, the patch has a temporary liner. Drugs are released from this by a combination of diffusion and membrane permeability.

Reservoir type:

Over the single-layer and multilayer drugs-in-adhesive systems, the reservoir TDDS has a separate drug layer. In addition, there is an adhesive layer separating the drug layer from the liquid compartment. Polymer membranes made of vinyl acetate are used to control the rate of drug release on the surface of a shallow compartment made of metallic plastic laminate. There is also a backing layer on this patch. A zero-release rate is required for such a system.

Matrix type:

A semisolid matrix containing a drug suspension or solution forms the drug layer of the matrix system. The adhesive layer partially covers the drug layer in this patch. Monolithic devices are also known as patches.

Vapour Patch:

Vapour patches have an adhesive layer that adheres the several layers together as well as releases vapor. Essential oils are released from vapour patches for up to six hours and are chiefly used to relieve congestion. On the market, there are also vapour patches that improve sleep quality or help smokers quit.

Methodology in Making TDDS

The following are the methods do adopt for TDDS⁵

Asymmetric TPX membrane method:

Patch prototypes can be made. As a backing membrane, we will use heat-stable polyester film (type 1009, 3m) with a concave of 1 cm diameter (Chart 1).

Chart 1: Preparation method by Asymmetric TPX membrane method

Circular Teflon mould method:

This approach proceed as follows (chart 2)

Chart 2: Preparation method by Circular Teflon mould method

In a laminar flow hood model with an air speed of 0.5 m/s, the molds are placed on a flat surface and covered with an inverted funnel to prevent solvent vaporization. The solvent evaporates after 24h. To avoid aging effects, it is suggested that the desiccators contain silica gel for an additional 24h at 25±0.5°C before evaluating dried films. A week after preparing dried films should be sufficient for evaluation.

Mercury substrate method:

This approach is proceeded as follows (chart 3)

Chart 3: Mercury substrate method

IPM membranes method:

This tactic runs as described in chart 4.

Chart 4: IPM membranes method

EVAC method:

To prepare the target TDDS, 1% Carbopol Reservoir gel, Polyethylene (PE), ethylene vinyl acetate copolymer (EVAC) membranes can be used as rate control membranes. If the drug is insoluble in water, Propylene Glycol is used for the preparation of the gel (chart 5).

Chart 5: EVAC method

Aluminium supported adhesive film method:

When the loading dose is more than 10 mg, TDDS may produce uneven matrices. An aluminum-backed adhesive film is a suitable method. The solvent of choice is chloroform because most drugs and adhesives can be dissolved in it (chart 6).

Chart 6: Aluminium supported adhesive film method

ADVANTAGES OF TDDS:

TDDS have the following merits and pitfalls^{6, 7}.

· Avoids first-pass metabolism.

· Gastrointestinal compatibility

· Activity duration should be extended and predictable.

· Reduce undesirable side effects.

· Allows for the use of drugs with a short biological half-life and a narrow therapeutic window.

· Enhance the efficacy of therapy.

· With the removal of the patch, drug administration stops.

· Patients who can’t take oral medications can take their medications by an alternate route.

· Easy, non-invasive, and painless application increases patient compliance and comfort.

Disadvantages of TDDS:

· Drugs can currently only be delivered in small, lipophilic quantities.

· The patch size limits the amount of drug molecules, so they must be potent.

· Very low or very high partition coefficients prevent drugs from reaching the bloodstream.

· Due to their low miscibility in both water and fat, highly melting drugs can be given this way.

· Drugs, adhesives, or other excipients in the patch formulation can cause erythema, itching, and local edema.

The past successful attempts so made in TDDS were illustrated in table 1.

Table 1: Hitherto approaches and methods adopted in making TDDS

Drug	Polymer	Type	Reference
Gatifloxacin	Carboxy Methyl Cellulose	Matrix	⁸Ullah et al., 2021
Gliclazide	Duro Tak 87-4098	Ionic liquid	⁹Zhou et al., 2021
Propranolol	Eudragit RL	Matrix	¹⁰Musazzi et al., 2021
Pregabalin	Hydroxypropyl methylcellulose (HPMC), Polyvinyl alcohol (PVA) and Polyvinylpyrrolidone (PVP)	Matrix	¹¹Bhatia et al., 2021
Cissus quadrangularis	HPMC E-15	Matrix	¹²Das et al., 2021
Rotigotine	Duro Tak 87-2054 and Durotak 6908	Matrix	¹³Shailesh et al., 2020
Lornoxicam	HPMC	Matrix	¹⁴Sharma et al., 2020
Rasagiline Mesylate	Eudragit L 100	Matrix	¹⁵Hulyalkar et al., 2020
Piroxicam	HPMC, PVP and Ethyl Cellulose (EC)	Matrix	¹⁶Mahajan et al.,2020
Mefenamic acid	Eudragit RL	Matrix	¹⁷Suksaeree et al., 2019
Benzylpiperidine	Duro Tak 87-2516 and Duro Tak 87-2287	Matrix	¹⁸Ganti et al.,2019
Eptazocaine	Eudragit E	Matrix	¹⁹Furuishi et al.,2019
Estrogen	Chitosan	Matrix	²⁰Chauhan et al., 2019
Tetrahydro Curcumin	Poly (ethylene glycol) poly(ε-caprolactone) copolymers (PEG-PCL)	Matrix	²¹Rramaswamy et al., 2018
Timolol	Ethyl Cellulose and EudragitRS-100	Matrix	²²Panchayya et al.,2018
Ketoprofen	PEG 400, PVP K30	Matrix	²³Yani et al., 2018
Nicotine	Ethyl cellulose and Eudragit RL-100	Matrix	²⁴Sunitha et al., 2018
Ibuprofen	Poly Urethane Ether	Matrix	²⁵Tombs et al., 2018
Topiramate	Eudragit L-100	Matrix	²⁶Cherukuri et al., 2017
Fentanyl	Eudragit L 100, HPMC K 4 M and HPMC K15M	Matrix	²⁷Sandhya et al., 2017
Irbesatran	Poly Vinyl alcohol	Matrix	²⁸Srilakshmi et al., 2017
Seligiline	(HPMC), PVA and Methyl Cellulose (MC)	Matrix	²⁹Sandip et al., 2017
Rivastigmine	Chitosan	Matrix	³⁰Sadeghi et al., 2016
Atenolol	HPMC K4M and PVP	Matrix	³¹Budhathoki et al.,2016
Tamoxifen	Poly Sebacic Acid- co-ricinoleic acid	Reservoir	³²Saleem et al.,2016
Mentha	Chitosan	Reservoir	³³Saleem et al., 2016
Doneprazil	Eudragit S-100 and HPMC	Matrix	³⁴Madan et al., 2015
Fluoxetine	Duro Tak 87-502	Matrix	³⁵Jung et al., 2015
Isosorbid Dinitrate	Polyethylene and Ethylene-vinyl acetate (EVAC)	Reservoir	³⁶Zhan et al., 2015
Zingiber	Chitosan	Reservoir	³⁷Suksaeree et al., 2015
Cefdinir	Polymethacrylate and PVP	Matrix	³⁸Kanabar et al., 2015
Insulin	HPMC and PVP K30	Matrix	³⁹Sadhasivam et al., 2015
Nitroglycerine	Duro-Tak 2516 and Duro-Tak 2054	Matrix	⁴⁰Savoji et al., 2014
Lidocaine	Lysine modified Chitosan	Matrix	⁴¹Wang et al., 2013
Stavudine	Eudragit RX-100 and Eudragit RL-100	Matrix	⁴²Kumar et al.,2013
Ondansetron	PVA and PVP	Matrix	⁴³Mohd et al., 2012
Fexofenadine	HPMC and EC	Matrix	⁴⁴Chaudhary et al., 2012
Scopolamine	Hydroxy Propyl Cellulose	Matrix	⁴⁵Shaoul et al., 2012
Clonidine	(Eudragit L-100-55 PVP K-30, 3:1)	Matrix	⁴⁶Verma et al., 2012
Aceclofenac	Ethyl Cellulose	Matrix	⁴⁷Patel et al., 2012
Aspirin	HPMC	Reservoir	⁴⁸Banerjee et al., 2012
Budesonide	Eudragit RL 100, Ethyl Cellulose and PVP	Matrix	⁴⁹Lade et al., 2011
Repaglinide	HPMC K100 and PVP	Matrix	⁵⁰Prajapati et al., 2011
Nifedipine	PVA and PVP	Matrix	⁵¹Ahmed et al., 2010
Curcumin	HPMC and Ethyl Cellulose	Matrix	⁵²Saraswathi et al., 2010
Flurbiprofen	HPMC	Reservoir	⁵³Charoo et al., 2008
Glipizide	PVP, Eudragit RL-100 and Eudragit RS-100	Matrix	⁵⁴Mutalik et al., 2006
Metoclopramide	PVA and PVP	Matrix	⁵⁵Saxena et al, 2006
Ephedrine	Eudragit RL-100 and Eudragit RS-100	Reservoir	⁵⁶Jain et al., 1990

CONCLUSION:

TDDS has gained realistic potential as the next-generation drug delivery system for the prolonged, controlled release of both hydrophobic and hydrophilic drugs, efficiently addressing the low oral bioavailability and inconvenience of injections. Future research will be aimed at better transdermal device design with a greater understanding of the different mechanisms of biological interactions with permeation enhancers and improving the flux for a wide variety of molecules, especially macromolecules and vaccines, using cost-effective, novel physical enhancement techniques along with the existing chemical enhancers.

ACKNOWLEDGMENTS:

The authors are thankful to RIPER management for the encouragement.

REFERENCES:

1. Ahad HA, Kumar BP, Haranath C, Reddy KS. Fabrication and evaluation of glimepiride Ficus benghalensis fruit mucilage matrix transdermal patches. International Journal of Chemical Sciences. 2009;7(4):2294-8.

2. Swetha T, Ahad HA, Reddy KK, Sekhar AC, Sivaji S, Kumar BA. Formulation and in-vitro permeation studies of Ketoprofen-Ficus reticulata fruit mucilage transdermal patches. Der Pharmacia Lettre. 2010;2(6):190-9.

3. Ahad HA, Kiranmaye N, Yasmeen R, Ruksana H, Muneer S. Designing and Evaluation of Glimepiride Ficus glomerata Fruit Mucilage Matrix Transdermal Patches. Asian Journal of Chemistry. 2010 Apr 20;22(4):2935.

4. Shravani Y, Ahad HA, Haranath C, gari Poojitha B, Rahamathulla S, Rupasree A. Past Decade Work Done on Cubosomes Using Factorial Design: A Fast-Track Information for Researchers. (2021). Int. J. Life Sci. Pharma Res.;11(1): P124-135.

5. Anuradha CM, Ahad HA, Sreekanth K, Abhilash A, Prabhuraj KJ, Swapna K. Pharma Research Library International Journal of Medicine and Pharmaceutical Research 2013, Vol. 1 (1): 127-134.

6. Ahad HA, Sreeramulu J, Bindu VH, Ramyasree P, Padmaja BS, Sravanthi M. Isolation and physicochemical characterization of Ficus reticulata fruit mucilage. International Journal of Green Pharmacy (IJGP). 2011;5(2).

7. Ahad HA, Reddy BK, Ishaq BM, Kumar CH, Kumar CS. Fabrication and in vitro evaluation of glibenclamide Abelmoschus esculentus fruit mucilage-controlled release matrix tablets. Journal of Pharmacy research. 2010;3(5):943-6.

8. Ullah W, Nawaz A, Akhlaq M, Shah KU, Latif MS, Alfatama M. Transdermal delivery of gatifloxacin carboxymethyl cellulose-based patches: Preparation and characterization. Journal of Drug Delivery Science and Technology. 2021 Dec 1;66: 102783.

9. Zhou B, Liu S, Yin H, Qi M, Hong M, Ren GB. Development of Gliclazide ionic liquid and the transdermal patches: an effective and noninvasive sustained release formulation to achieve hypoglycemic effects. European Journal of Pharmaceutical Sciences. 2021 Jun 17:105915.

10. Musazzi UM, Gennari CG, Franzè S, Minghetti P, Cilurzo F. Printing of cutaneous patches loaded with propranolol for the treatment of infantile haemangiomas. Journal of Drug Delivery Science and Technology. 2021 Dec 1;66: 102767.

11. Bhatia C, Sachdeva M, Bajpai M. Formulation and evaluation of transdermal patch of pregabalin. International Journal of Pharmaceutical Sciences and Research. 2012 Feb 1;3(2):569.

12. Das R, Kolhe SN, Patil A, Wadher KA, Umekar M. Development and evaluation of transdermal patches with cissus quadrangularis plant extract. Int. J. Life science and Pharma Res. 2018 Apr 1;8(2), 29-34.

13. Shailesh T. Prajapati, Vipul Bhai Mandi. Formulation Development of Rotigotine Transdermal system using Dot-Matrix Technology. International Journal of Pharmaceutical Drug Sciences and Research. 2020. Volume 12 Issue 4. 404-414.

14. Sharma N, Sharma S, Kaushik R. Formulation and Evaluation of Lornoxicam Transdermal patches using various Permeation Enhancers. International Journal of Drug Delivery Technology. 2019 Dec 22;9(04):597-607.

15. Hulyalkar S, Shivakumar HN, Patil AS, Rao R. The Formulation and Evaluation of Rasagiline Mesylate Transdermal Patch for Enhanced Topical Delivery: Rasagiline Mesylate Transdermal Patch for Enhanced Topical Delivery. Journal of Tropical and Infectious Diseases. 2020 Aug 11;1(1), 1-6.

16. Mahajan NM, Zode GH, Mahapatra DK, Thakre S, Dumore N, Gangane PS. Formulation development and evaluation of transdermal patch of piroxicam for treating dysmenorrhoea. J Appl Pharm Sci. 2018 Nov;8(11):35-41.

17. Suksaeree J, Piamsap K, Paktham S, Kenprom T, Monton C, Pichayakorn W. Formulation development of matrix type transdermal patches containing mefenamic acid: physicochemical characterization and in vitro release evaluation. Monatshefte für Chemie-Chemical Monthly. 2017 Jul;148(7):1215-1222.

18. Ganti SS, Bhattaccharjee SA, Murnane KS, Blough BE, Banga AK. Formulation and evaluation of 4-benzylpiperidine drug-in-adhesive matrix type transdermal patch. International journal of pharmaceutics. 2018 Oct 25;550(1-2):71-78.

19. Furuishi T, Kunimasu K, Fukushima K, Ogino T, Okamoto K, Yonemochi E, Tomono K, Suzuki T. Formulation design and evaluation of a transdermal drug delivery system containing a novel eptazocine salt with the Eudragit E adhesive. Journal of Drug Delivery Science and Technology. 2019 Dec 1;54: 101289.

20. Chauhan SB, Naved T, Parvez N. Formulation, and development of transdermal drug delivery system of ethinylestradiol and testosterone: in vitro evaluation. International Journal of Applied Pharmaceutics. 2019 Jan 7:55-60.

21. Rramaswamy R, Mani G, Venkatachalam S, Venkata RY, Lavanya JS, Choi EY. Tetrahydro curcumin loaded PCL-PEG electrospun transdermal nanofiber patch: preparation, characterization, and in vitro diffusion evaluations. J Drug Deliv Sci Technol. 2018 Apr 1;44: 342-348.

22. Panchayya Hiremath SS, Reddy JJ, Jamakandi VG. Design and evaluation of transdermal patches of timolol maleate. Current drug delivery. 2018 Jun 1;15(5):658-663.

23. Yani F, Arianto A, Noersal R. Formulation of Ketoprofen Transdermal Solid Dispersion Patch as an Analgesic and Anti-Inflammatory. Asian Journal of Pharmaceutical Research and Development. 2020 Jun 15;8(3):51-8.

24. Sunitha C. Formulation and evaluation of nicotine transdermal patches by the using of hydrophilic and hydrophobic polymers. World journal of pharmaceutical Research, 2018, 7 (16); 1101-1115.

25. Tombs EL, Nikolaou V, Nurumbetov G, Haddleton DM. Transdermal delivery of ibuprofen utilizing a novel solvent-free pressure-sensitive adhesive (PSA): TEPI® technology. Journal of pharmaceutical innovation. 2018 Mar;13(1):48-57.

26. Cherukuri S, Batchu UR, Mandava K, Cherukuri V, Ganapuram KR. Formulation, and evaluation of transdermal drug delivery of topiramate. International journal of pharmaceutical investigation. 2017 Jan;7(1):10.

27. K. Sandhya Rani, Sunil Reddy, A.Venkatesham. Formulation development and invitro evaluation of fentanyl patches for transdermal drug delivery system. Journal of Pharmaceutical and Biological Sciences, 2017; 5(5):188-193.

28. Srilakshmi A, Teja VR, Lakshmi K, Thippesh M, Salma SU, Nagendrababu B. Formulation and evaluation of transdermal patches of Irbesartan. Indian Journal of Research in Pharmacy and Biotechnology. 2017;5(3):212-215.

29. Sandip A. Murtale, Doddayya Hiremath, Vishnu A. Kangralkar, Veerrendra C. Yeligar, Sachinkumar V. Patil, Shitalkumar S. Patil Development and Evaluations of Transdermal Delivery of Selegiline Hydrochloride. International Journal of Innovative Science and Research Technology. 2017; 2 (6), 391-404.

30. Sadeghi M, Ganji F, Taghizadeh SM, Daraei B. Preparation and characterization of rivastigmine transdermal patch based on chitosan microparticles. Iranian journal of pharmaceutical research: IJPR. 2016;15(3):283.

31. Budhathoki U, Gartoulla K, Shakya S. Formulation and evaluation of transdermal patches of atenolol. Indonesian Journal of Pharmacy. 2016 Dec 23;27(4):196.

32. Saleem MN, Adhyapak AA, Desai BG. Formulation and evaluation of liposomal transdermal patch for targeted drug delivery of tamoxifen citrate for breast cancer. Indian Journal of Health Sciences and Biomedical Research (KLEU). 2016 Jan 1;9(1):40.

33. Saleem MN, Idris M. Formulation design and development of a unani transdermal patch for antiemetic therapy and its pharmaceutical evaluation. Scientifica. 2016 Jun 15;2016, 1-5.

34. R Madan J, S Argade N, Dua K. Formulation and evaluation of transdermal patches of donepezil. Recent patents on drug delivery & formulation. 2015 Apr 1;9(1):95-103.

35. Jung E, Lee EY, Choi HK, Ban SJ, Choi SH, Kim JS, Yoon IS, Kim DD. Development of drug-in-adhesive patch formulations for transdermal delivery of fluoxetine: In vitro and in vivo evaluations. International journal of pharmaceutics. 2015 Jun 20;487(1-2):49-55.

36. Zhan X, Mao Z, Chen S, Chen S, Wang L. Formulation and evaluation of transdermal drug-delivery system of isosorbide dinitrate. Brazilian Journal of Pharmaceutical Sciences. 2015 Apr; 51:373-82.

37. Suksaeree J, Charoenchai L, Madaka F, Monton C, Sakunpak A, Charoonratana T, Pichayakorn W. Zingiber cassumunar blended patches for skin application: Formulation, physicochemical properties, and in vitro studies. asian journal of pharmaceutical sciences. 2015 Jul 1;10(4):341-9.

38. Kanabar VB, Patel VP, Doshi SM. Formulation and evaluation of transdermal patch of Cefdinir with various polymers. The Pharma Innovation. 2015 Aug 1;4(6, Part B):74.

39. Sadhasivam LI, Dey N, Francis AP, Devasena T. Transdermal patches of chitosan nanoparticles for insulin delivery. Int J Pharm Pharm Sci. 2015;7(5):84-8.

40. Savoji H, Mehdizadeh A, Ramazani Saadat Abadi A. Transdermal nitroglycerin delivery using acrylic matrices: design, formulation, and in vitro characterization. International Scholarly Research Notices. 2014;2014, 1-9.

41. Wang Y, Su W, Li Q, Li C, Wang H, Li Y, Cao Y, Chang J, Zhang L. Preparation and evaluation of lidocaine hydrochloride-loaded TAT-conjugated polymeric liposomes for transdermal delivery. International journal of pharmaceutics. 2013 Jan 30;441(1-2):748-756.

42. Kumar SS, Behury B, Sachinkumar P. Formulation and evaluation of transdermal patch of Stavudine. Dhaka University Journal of Pharmaceutical Sciences. 2013 Sep 2;12(1):63-69.

43. Mohd F, Bontha LS, Bontha VK, Vemula SK. Formulation and Evaluation of Transdermal Films of Ondansetron Hydrochloride. MOJ Bioequiv Availab. 2017;3(4):00039.

44. Chaudhary H, Saini S, Singh G. Formulation and evaluation of fexofenadine hydrochloride transdermal patch. Journal of Drug Delivery and Therapeutics. 2012 Sep 15;2(5), 20-23.

45. Shaoul E, Ayalon A, Tal Y, Lotan T. Transdermal delivery of scopolamine by natural submicron injectors: in-vivo study in pig. PLoS One. 2012 Feb 21;7(2): e 31922.

46. Verma A, Verma B, Prajapati S, Tripathi S. Formulation and evaluation of transdermal therapeutic system of matrix type clonidine hydrochloride. Der Pharmacia Letter. 2012;4(4):1137-42.

47. Patel RP, Patel G, Patel H, Baria A. Formulation and evaluation of transdermal patch of aceclofenac. Research Journal of Pharmaceutical Dosage Forms and Technology. 2009;1(2):108-15.

48. Banerjee A, Chakraverty MH, Dey S, Basak D, Biswas C. Preparation and evaluation of aspirin transdermal patch using HPMC. Int J Pharma Sci Rev Res. 2012;15(1):45-6.

49. Lade UB, Amgaonkar YM, Chikhale RV, Biyani DM, Umekar MJ. Design, formulation and evaluation of transdermal drug delivery system of budesonide. Pharmacology & Pharmacy. 2011 Jul 26;2(03):199.

50. Prajapati ST, Patel CG, Patel CN. Formulation and evaluation of transdermal patch of repaglinide. International Scholarly Research Notices. 2011; 2011, 1-9.

51. Ahmed MG, Kumar KG, Kumar SB. Formulation and evaluation of nifedipine transdermal patches. Journal of Pharmacy Research. 2010;3(8):1785-7.

52. Saraswathi R, Krishnan PN, Dilip C, Ali TS. Formulation and evaluation of transdermal patches of curcumin. Der Pharmacia Lettre. 2010;2(5):117-26.

53. Charoo NA, Shamsher AA, Kohli K, Pillai K, Rahman Z. Improvement in bioavailability of transdermally applied flurbiprofen using tulsi (Ocimum sanctum) and turpentine oil. Colloids and surfaces B: Biointerfaces. 2008 Sep 1;65(2):300-7.

54. Mutalik S, Udupa N, Kumar S, Agarwal S, Subramanian G, Ranjith AK. Glipizide matrix transdermal systems for diabetes mellitus: Preparation, in vitro and preclinical studies. Life sciences. 2006 Sep 13;79(16):1568-77.

55. Saxena M, Mutalik S, Reddy MS. Formulation and evaluation of transdermal patches of metoclopramide hydrochloride. Indian Drugs. 2006;43(9):740-5.

56. Jain SK, Vyas SP, Dixit VK. Effective and controlled transdermal delivery of ephedrine. Journal of Controlled Release. 1990 May 1;12(3):257-63.

Received on 20.11.2021 Modified on 09.01.2022

Res. J. Pharma. Dosage Forms and Tech.2022; 14(2):157-162.

DOI: 10.52711/0975-4377.2022.00025