EFFECT OF TRANSDERMAL PATCH ON SKIN

Effect of Transdermal Patch on Skin

Skin [1 - 3] is a very important site of drug application for each native and general effect. The skin is that the largest organ within the body; it protects against the flow of poisons and also the flow of water and is basically impermeable to the penetration of foreign molecules. Human skin consists of 3 main layers: the stratum, dermis, and layer. The stratum [4, 5], above all the horny layer, acts because the major barrier to drug absorption. The horny layer contains solely 2 hundredth of water and could be an extremely oleophilic membrane; it is 10–20 μm thick depending on its state of association. The thickness of the stratum varies from zero.06 millimeter on eyelids to 0.8 millimeter on the soles of the feet.

An applied drug should traverse these structural layers, encountering many oleophilic and deliquescent domains on the way to the corneum [6 - 10] wherever absorption into the circulation is fast owing due to the large capillary bed. Removing the corneum speeds the diffusion of little soluble molecules into the circulation by up to a thousand times or else, deliquescent compounds will reach the corneum via shunt pathways like hair follicles, sweat glands, nerve endings, and blood and liquid body substance vessels. These routes contribute minimally to steady-state drug flux. The corneum is that the thickest layer of the skin (3–5 mm) [11, 12] and possesses hair follicles, sweat glands, nerve endings, and blood and liquid body substance vessels. It acts as the general absorption web site for medicine.

There are variations between people within the rate at that drugs are absorbed via the skin owing to factors like thickness of the corneum, skin association, underlying skin diseases[13, 14] or injuries, ethnic variations, and vital sign.

The idea of percutaneous drug delivery system (delivering medicine through skin) is recent, because the use of it is reported back in16th century B.C [15 - 17]. Throughout the last years, developments in percutaneous drug delivery are incremented focusing primarily on overcoming issues related to the skin barrier properties [18].

Transdermal drug delivery system [19] is the trendy delivery system to deliver the drug by passing the first pass metabolism drawback. Once the patch is applied, the drug begins flowing through the skin into the blood at a rate regulated by the membrane, pre-programmed to stay the drug at levels that give effectiveness with acceptable adverse effects.

Currently over thirty five TDDS merchandise are approved in us for the wide range of condition like high blood pressure, angina, sickness, severe pain, native pain[20 - 25] etc.

Transdermal drug delivery systems having several advantages and disadvantages it includes:

1. Longer length of action leading to a decrease in dosing frequency [26].

2. Increased convenience to administer medication which might otherwise need frequent dosing.

3. Improved bioavailability [27, 28].

4. More uniform plasma levels [29].

5. Reduced facet effects and improved medical aid attributable to maintenance of plasma levels up to the tip of the dosing interval [30].

6. Flexibility of terminating the drug administration by merely removing the patch from the skin.

7. Improved patient compliance and luxury through non- invasive, painless [31] and easy application.

8. Prevent the first-pass metabolism of drug [32].

9. When drug is not possible to require orally like in continuous unconditioned reflex condition and unconscious patient.

10. Possibility that a neighborhood irritation at the location of application.

11. Erythema, itch [33] and edema [34, 35] may be caused by the drug, the adhesive, or different excipients within the patch formulation.

Transdermal patch [5] consists of 4 layers of skinny, versatile membranes:

1. Impermeable backing membrane: Protects the patch from the setting.

2. Drug reservoir: Drug in direct contact with the discharge liner.

3. Rate-controlling membrane: Controls the discharge of the drug from reservoir and multi-layer patches, and

4. Adhesive: Adheres the elements of the patch along and sticks the patch to the skin.

Several differing types of transcutaneous patches [36 - 38] are presently available:

1. Single-layer drug-in-adhesive patch: The adhesive layer adheres the various layers on and sticks the system to the skin; that is chargeable for the drug unleash.

2. Multi-layer drug-in-adhesive patch: Each adhesive layers are accountable for removing of the drug; one in all the layers is for immediate unharness and also the alternative layer is to manage unharness of the drug from a reservoir.

3. Reservoir patch: It features a separate drug layer as a liquid compartment, containing a drug suspension, between a backing layer and a rate-controlling membrane; this leads to a zero-order rate of unharness. Reservoir patches mustn't be cut.

4. Matrix patch: Features a drug layer of a semi-solid matrix containing a drug answer or suspension spread inside a chemical compound pad in direct contact with the skin. The adhesive layer during this patch surrounds the drug layer part overlaying it.

Various methods for skin enhancement of TDDS:

1. Active/ vehicle interaction

• Drug/ prodrug

• Chemical potential

• Ion pairs

• Eutectic system

2. Vesicles and particles

• Liposomes and analogues [39,40]

• Microemulsions [41]

• Lipid nanoparticles [42]

• High velocity particles

3. Strateum corneum bypassed/ removed

• Microneedles [43-46]

• Follicular delivery

4. Electrically assisted methods

• Iontophoresis [47]

• Electroporation [48-50]

• Phonophoresis [51,52]

• Photomechanical waves [53-55]

• Magnetophoresis [56]

Factors affecting transdermal drug delivery system:

1. Physicochemical properties of penetrants: pHconditions, partition coefficient, penetrant concentration.

2. Physicochemical properties of drug delivery system: release characteristics, composition of TDDS

3. Physiological and pathological conditions of the skin: skin hydration, skin temperature, lipid film.

Conclusion

Transdermal Drug Delivery System (TDDS) is another to traditional delivery by lowering the issues related to the oral and parental administration of medication. TDDS additionally bypasses the first pass metabolism and results in low bioavailability of the drug, to achieving a constant\controlled unharness of drug with minimize facet effects earned by exploitation kind of polymers (applied as a nano-carrier for microspheres, nanoparticles). Another necessary advantage is easy and painless application. The patch can also be used for management of acute and chronic pain.

References

1. Branvold A and Carvalho M. Pain Management Therapy: The Benefits of Compounded Transdermal Pain Medication. J Gen Practice. 2014; 2:188.
2. Shakeel F et al. Comparative Pharmacokinetic Profile of Aceclofenac from Oral and Transdermal Application. J Bioequiv Availab. 2009; 1:013-017.
3. Jampilek J. Transdermal Application of Drugs and Techniques Affecting Skin Barrier. J Bioequiv. 2013; 5:233-235.
4. Silva HR et al. Surfactant-based Transdermal System for Fluconazole Skin Delivery. J Nanomed Nanotechnol. 2014; 5:231.
5. Barakat N et al. Formulation Design of Indomethacin-Loaded Nanoemulsion For Transdermal Delivery. Pharm Anal Acta. 2011; S2:002.
6. Malika V et al. Nano-Carrier for Accentuated Transdermal Drug Delivery. J Develop Drugs. 2014; 3:121.
7. Elshafeey AH et al. Enhanced Bioavailability of Fenoterol Transdermal Systems in Rabbits. J Bioequiv Availab. 2011; 3:097-100.
8. Pandey A et al. Role of Surfactants as Penetration Enhancer in Transdermal Drug Delivery System. J Mol Pharm Org Process Res. 2014; 2:113.
9. Lu Y et al. Development and Optimization of a RP-HPLC Method to Quantify Midazolam in Rat Plasma after Transdermal Administration: Validation and Application in Pharmacokinetic Study. Pharm Anal Acta. 2015; 6:329.
10. Szczygiel M et al. Real-time Non-invasive Transdermal Monitoring of Photosensitizer Level in vivo for Pharmacokinetic Studies and Optimization of Photodynamic Therapy Protocol. J Anal Bioanal Tech. 2014; 5:22.
11. Svensson CK. Biotransformation of Drugs in Human Skin. Drug Metab Dispos. 2009; 37:247-253.
12. Patel D et al. Transdermal drug delivery system: review. Int J Biopharm & Tox Research. 2011; 1:61-80.
13. Lauretti GR et al. Transdermal Ketamine and S(+)-Ketamine as Adjuvants Following Orthopaedic Surgery under Bupivacaine Spinal Anaesthesia. 2014.
14. Lakshmi PK et al. Transdermal Permeation Enhancement of Lamotrigine Using Terpenes. J Pharma Care Health Sys. 2014; 1:103.
15. Lin SL et al. Using Topical Applications of Tamoxifen and a Combination of Phytonutrients Based on Breast MRI to Inhibit Estrogen-Related Proliferation of Human Breast Tissue. Pharm Anal Acta. 2014; 5:281.
16. Delicou S et al. Hyper-Acute Toxic Delirium in a Patient Using Transdermal Fentanyl. J Pain Relief. 2013; 2:125.
17. Kamimura M et al. Transdermal Application of Steroid to Cervical Trachea for the Cough in Patients with Bronchial Asthma and Cough Variant Asthma-A Pilot Study. J Allergy Ther. 2013; 4:152.
18. Basu Sarkar A et al. Chemical Stability of Progesterone in Compounded Topical Preparations using PLO Transdermal Creamâ„¢ and HRT Creamâ„¢ Base over a 90-Day Period at Two Controlled Temperatures. J Steroids Horm Sci. 2013; 4:114.
19. El-Khordagui LK Microneedles: An Emerging Approach for Active Transdermal Delivery of Insulin. J Bioequiv. 2012; 4:xxxi-xxxiii.
20. Meier-Davis SR, et al. Comparison of Metabolism of Donepezil in Rat, Mini-Pig and Human, Following Oral and Transdermal Administration, and in an in vitro Model of Human Epidermis. J Drug Metab Toxicol. 2012; 3:129.
21. Parthasarathi D et al. Analysis of Pharmacokinetic & Pharmacodynamic Models in Oral and Transdermal Dosage Forms. J Bioequiv 2011; 3:268-276.
22. Wujian J et al. A Simple Protein Precipitation-based Simultaneous Quantification of Lovastatin and Its Active Metabolite Lovastatin Acid in Human Plasma by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry using Polarity Switching. 2015.
23. Agatonovic-Kustrin S et al. Biorelevant Dissolution Studies of Pioglitazone HCL Immediate Release Tablets and the Determination of an In Vitro In Vivo Correlation. J Bioequiv 2015; 7:086-089.
24. Hendawy OM et al. Effect of Atorvastatin and Vitamin D on Freund’s Adjuvant-Induced Rheumatoid Arthritis in Rat. J Bioequiv. 2015; 7:090-094.
25. Pillay TK et al. The Influence of Culture on Chronic Pain: A Collective Review of Local and International Literature . J Psychiatry. 2015; 18:234.
26. Chein YW. Transdermal drug delivery & delivery systems. Novel drug delivery systems. New York: Marcel Dekker. 1992; 301-380.
27. Santos FI. The Key in the Initial Success of Chronic Pain Treatment. J Yoga Phys Ther. 2014; 4:163.
28. Nalamachu S et al. Acute Pain Management in the Emergency Department: Emphasis on NSAIDs. Emergency Med. 2013; 4:171.
29. Reszka E et al. Expression of Bitter Taste Receptors in the Human Skin In Vitro. J Clinic Res Bioeth. 2015; 6:218.
30. Vyas SP and Khar RK. Transdermal drug delivery. Controlled drug delivery-concepts and advances. New Delhi, India: VallabhPrakashan. 2002; 411-447.
31. Rein H. Experimental electroendosmotic studies on living human skin. Z Biol. 1924; 81:124-128.
32. Walker RB and Smith EW. The role of percutaneous penetration enhancers. Adv Drug Deli Rev. 1996; 18: 295-301.
33. Barry BW. Lipid-protein-partitioning of skin penetration enhancement. J Control Release. 1991; 15:237-248.
34. Benson HA. Transdermal drug delivery: penetration enhancement techniques. Curr Drug Deliv. 2005; 2:23-33.
35. Finnin BC and Morgan TM. Transdermal penetration enhancers: applications, limitations, and potential. J Pharm Sci. 1999; 88:955-958.
36. Vasilev AE et al. Transdermal therapeutic systems for controlled drug release. Pharm Chem J. 2001; 35:613-626.
37. Barry BW. Novel mechanisms and devices to enable successful transdermal drug delivery. Eur J Pharm Sci. 2001; 14:101-114.
38. Ledger PW. Skin biological issues in electrically enhanced transdermal delivery. Adv Drug Deliv Rev. 1992; 9: 289-307.
39. Cooper ER. Increased skin permeability for lipophilic molecules. J Pharm Sci. 1984; 73:1153-1156.
40. Williams AC and Barry BW. Skin absorption enhancers. Crit Rev Ther Drug Carrier Syst 1992; 9:305-353.
41. Godavarthy SS et al. Design of improved permeation enhancers for transdermal drug delivery. J Pharm Sci. 2009; 98:4085-4099.
42. Schaefer H and Filaquier C [Skin metabolism] Pathol Biol (Paris). 1992; 40: 196-204.
43. Karande P and Mitragotri S Enhancement of transdermal drug delivery via synergistic action of chemicals. Biochim Biophys Acta. 2009; 1788:2362-2373.
44. Xu P and Chien YW. Enhanced skin permeability for transdermal drug delivery: physiopathological and physicochemical considerations. Crit Rev Ther Drug Carrier Syst. 1991; 8:211-236.
45. Changez M et al. Transdermal permeation of tetracaine hydrochloride by lecithin microemulsion: in vivo. Colloids Surf B Biointerf. 2006; 48:58-66.
46. Mei Z N, Chen HB, Weng T, Yang YJ, Yang X (2003) Solid lipidnanoparticle and microemulsion for topical delivery of triptolide. Eur J Pharm Biopharm 56: 189-196.
47. Pikal MJ. The role of electroosmotic flow in transdermal iontophoresis. Adv Drug Deliv Rev. 2001; 46:281-305.
48. Riviere JE and Heit MC. Electrically-assisted transdermal drug delivery. Pharm Res. 1997; 14:687-697.
49. Prausnitz MR. A practical assessment of transdermal drug delivery by skin electroporation. Adv Drug Deliv Rev. 1999; 35:61-76.
50. Prausnitz MR et al. Transdermal delivery of heparin by skin electroporation. Biotechnology (N Y). 1995; 13:1205-1209.
51. Mitragotri S et al. Transdermal drug delivery using low-frequency sonophoresis. Pharm Res. 1996;13:411-420.
52. Henry S et al. Microfabricated microneedles: a novel approach to transdermal drug delivery. J Pharm Sci. 1998; 87:922-925.
53. Vasilev AE et al. Transdermal therapeutic systems for controlled drug release. Pharm Chem J. 2001; 35:613-626.
54. Misra A et al. Needle-free, nonadjuvanted skin immunization by electroporation-enhanced transdermal delivery of diphtheria toxoid and a candidate peptide vaccine against hepatitis B virus. Vaccine. 1999; 18:517-523.
55. Mitragotri S et al. Transdermal drug delivery using low-frequency sonophoresis. Pharm Res. 1996; 13: 411-420.
56. Barry BW. Novel mechanisms and devices to enable successful transdermal drug delivery. Eur J Pharm Sci. 2001; 14:101-114.