INTRODUCTION:

1. Anatomy and structure of the human nail

Human fingernail gross anatomy consists of three structures. Initial from the outer structure, they are the nail plate, the nail bed, and the nail matrix (Figure 1). The nail plate is a thin (0.25 ‐ 0.6 mm for fingernails and up to 1.3mm for toenails), hard, yet slightly elastic, translucent, convex structure and is made up of approximately 25 layers of dead keratinized, flattened cells^[1]. They are strongly bound to one another via numerous intercellular links, membrane‐coating granules and desmosomes, which are cell structures, specialized for cell‐to‐cell adhesion and randomly arranged on the lateral sides of plasma membranes. The fingernail has a three‐layer structure (outer to inner) the dorsal, intermediate, and ventral layers, with a thickness ratio of approximately 3:5:2, respectively^[2].

2. Structure of the human nail apparatus

The nail apparatus consists of the nail bed, nail matrix, nail folds, and nail plate (Fig. 1A and 1B). The nail bed is a thin, soft, non-cornified epithelium, connected with the ventral layer of the nail plate and underlying papillary dermis. It is well perfuse by blood and lymphatic vessels. The nail matrix is situated directly under the proximal nail fold. The nail plate is continually produced by the nail matrix, which consists of highly proliferating epidermal cells^[3].

Cells become larger, more elongated, flatter, paler, and the nucleus disintegrates forming fragments in the horny layer. Nail growth in fingers is about 3 mm per month and in toes 1 mm per month, which means that a fingernail can be completely replaced in about 6 month and a toenail in about 12-18 month^[4,
5].

Fig 1A Radiograph of a fingertip (Received from

Huonder and Kamstra,

University Hospital Zurich)

Fig 1B Photograph of a fingertip

3. Structure of the nail plate

The nail plate consists of approximately 80-90 layers of dead, keratinized cells which are linked by desmosomal junctions and intercellular links. Superficial cells can be about one half as thick as cells of the deepest layer in the human nail plate ^{[6, 7]}. Also, the thickness o f the whole nail plate varies. The thickness increases from the proximal nail fold to the free edge of the nail plate. The nail plate can be divided into three layers: dorsal, intermediate, and ventral layer^[8]. The thickness ratio of the dorsal:intermediate:ventral layer is 3:5:2^[9]. According to the structure of the human nail plate, a concept proposed by Walters and Flynn^[10] that the nail plate behaves like a hydrophilic gel membrane remains nowadays.

DISEASES OF NAILS

The nail plate may appear abnormal as result of, a congenital defect, disease of skin with involvement of the nail bed, systematic disease, reduction of blood supply, local trauma, tumors of the nail fold or nail bed, infection of the nail fold, infection of the nail plate.

a. Paronychia: Infections of the nail fold can be caused by bacteria, fungi and some viruses. This type of infection is characterized by pain, redness and swelling of the nail folds. People who have their hands in water for extended periods may develop this condition, and it is highly contagious ^{[11, 12]}.

b. Pseudomonas: Bacterial infection can occur between the natural nail plate and the nail bed, and/or between an artificial nail coating and the natural nail plate. The after effects of this infection will cause the nail plate to darken and soften underneath an artificial coating. The darker the discoloration, the deeper into the nail plate layers the bacteria has traveled ^{[11, 12]}.

c. Fungal or yeast: This type of infection is characterized by onycholysis (nail plate separation) with evident debris under the nail plate. It normally appears white or yellowish in color, and may also change the texture and shape of the nail. The fungus digests the keratin protein of which the nail plate is comprised. ^{[11, 12]}

d. Tinea Unguis: Tinea Unguis or ringworm of the nail is characterized by nail thickening, deformity, and eventually results in nail plate loss. ^[11,
12]

e. Onychatrophia: It is atrophy or wasting away of the nail plate which causes it to lose its luster, become smaller and sometimes shed entirely. Injury or disease may account for this irregularity. ^{[11, 12]}

f. Onychogryphosis: Claw-type nails are characterized by a thickened nail plate and are often the result of trauma. This type of nail plate will curve inward, pinching the nail bed and sometimes require surgical intervention to relieve the pain. ^{[11, 12]}

g. Onychorrhexis: In this nails are brittle which often split vertically, peel and/or have vertical ridges. This irregularity can be the result of heredity, the use of strong solvents, including household cleaning solutions ^{[11, 12]}.

h. Onychauxis: This type of disease is evidenced by over-thickening of the nail plate and may be the result of internal disorders. ^{[11, 12]}

i. Leuconychia: This disease shows white lines or spots in the nail plate and may be caused by tiny bubbles of air that are trapped in the nail plate layers due to trauma. This condition may be hereditary and no treatment is required as the spots will grow out with the nail plate.^{[11, 12]}

j. Beau's Lines: Nails are characterized by horizontal lines of darkened cells and linear depressions. This disorder may be caused by trauma, illness, malnutrition or any major metabolic condition, chemotherapy or other damaging event, and is the result of any interruption in the protein formation of the nail plate.^{[11, 12]}

k. Koilonychia: It is usually caused through iron deficiency anemia, nails show raised ridges and are thin and concave.^{[11, 12]}

l. Melanonychia: Vertical pigmented bands, often described as nail 'moles', usually form in the nail matrix. It could signify a malignant melanoma or lesion. Dark streaks may be a normal occurrence in dark-skinned individuals.^[11,12]

m. Pterygium: It is the inward advance of skin over the nail plate, usually the result of trauma to the matrix due to a surgical procedure or by a deep cut to the nail plate. Pterygium results in the loss of the nail plate due to the development of scar tissue.^{[11, 12]}

n. Pterygium Inversum Unguis: It is an acquired condition characterized by a forward growth of the hyponychium live tissue firmly attached to the underside of the nail plate, which contains a blood supply and nerves. Possible causes are systemic, hereditary, or from an allergic reaction to acrylics or solvents.^{[11, 12]}

o. Psoriasis: Nails are characterized by raw, scaly skin and is sometimes confused with eczema. When it attacks the nail plate, it will leave it pitted, dry, and it will often crumble. The plate may separate from the nail bed and may also appear red, orange or brown, with red spots.^{[11, 12]}

p. Brittle Nails: It is characterized by a vertical splitting or separation of the nail plate layers at the distal (free) edge of the nail plate. In most cases, nail splitting and vertical ridges are characteristic of the natural aging process. This nail problem is also the result of overexposure to water and chemical solvents such as household cleaning solution. ^{[11, 12]}

q. Vertical Ridges: The nail plate grows forward on the nail bed in a 'rail and groove' effect, much like a train rides on its tracks. With age, the natural oil and moisture levels decline in the nail plate and this rail and groove effect becomes apparent. Ridged nails will improve through re-hydration of the nail plate with twice daily applications of good quality nail and cuticle oil containing Jojoba and Vitamin E. ^[11,
12]

r. Hematoma: It can happen from simply trapping your finger or toe in the car door to friction from improperly fitting or 'too-tight' shoes, or to a sports related injury. The nail bed will bleed due to this trauma, and the blood is trapped between the nail bed and the nail plate. Hematoma may result in nail plate separation and infection because the blood can attract fungi and bacteria. ^[11,12]

s. Nail Patella Syndrome: it is a rare genetic disorder involving nail and skeletal deformities (among a host of other related anomalies) that occurs in approximately 2.2 out of every 100,000 people. It is transmitted as a simple autosomal dominant characteristic in the ABO blood group. ^{[11, 12]}

Paronychia Infection

Pseudomonasbacterium trapped between the nail

Fungal Infection of the nail plate

Ringworm of the nail

Nail Atrophy

Ingrown Toenail

Vertical Split in the nail plate

Onychauxis

Leuconychia

Beaus Lines

Koilonychia

Melanonychia

Pterygium

Pterygium Inversum Unguis

Psoriasis of the nails

Brittle nails

Vertical ridges

Hematoma nail

Nail Patella Syndrome

t. Onychomycosis: Onychomycosis is a chronic fungal infection of the nail. It is caused mostly by dermatophytes, particularly Trichophyton rubrum, as well as by nondermatophyte yeasts, of which Candida albicans is the most common, or moulds. ^[13] Prevalence is higher among elder people or one with a poor peripheral circulation, in male, diabetic and HIV positive patients, and patients who are treated by immunosuppressant drugs. ^{[14, 15, 16]} The most frequently reported symptoms are discoloration, thickening, and deformity of the nails (Fig. 2). Onychomycosis can be classified in several categories depending on where the infection begins. ^{[17, 18, 19]}

(I) Distal and lateral subungual onychomycosis is the most common type of onychomycosis. The organisms access to the nail unit from the hyponychium and invade first distal nail bed, but then usually spread to proximal nail bed (Fig. 2A).

(II) Superficial white onychomycosis is developed when the surface of the nail plate is the initial site of invasion. Small superficial white patches with distinct edges can be distinguished in the nail plate, which can spread as the disease progresses (Fig. 2B).

(III) Proximal subungual onychomycosis starts when causative agent penetrates through the proximal nail fold, where the stratum corneum is the primary site of the fungal invasion. This type of onycomycosis is less common (Fig. 2C).

(IV) Total dystrophic onychomycosis is an advanced form of the previously described types. It is characterized by total destruction of the nail plate (Fig. 2D)

2A 2B

2C 2D

Fig.2 Types of onychomycosis (Dawber and Baran, 1984a)

TREATMENT OF NAIL DISORDERS

The main challenge associated with developing topical treatments for nail disorders is to deliver the active (antifungal) in therapeutically effective concentrations to the site of infection, which is often under the nail. Some research efforts have focused on improving penetration by chemically modifying the nail matrix. ^{[20, 21]}

Potential nail penetration enhancers

Keratolytic agents such as salicylic acid, urea and papain have been investigated as potential nail penetration enhancers. The primary mechanism for enhancement of nail penetration as thought to be by reduction of disulphide linkages in the nail keratin matrix. ^{[20, 21]}

Amino acid derivatives

Mercaptan compounds have been established to reduce keratin in human hair via a sequence of two reversible, nucleophilic displacements. High concentration of the mercaptan and alkaline pH favor the forward reaction due to the increased formation of the mercaptide anion required for reduction. ^{[20, 21]}

Pyrithione and its derivative

Pyrithion (2-mercaptopyridine-1-oxide) is a fungicidal and bactericidal agent. Compounds containing a -SH group are themselves oxidized while reducing disulphide linkages in nail keratin. ^{[20, 21]}

Sulfites and Bisulphites

Sulphites and bisulphites are known to be reducers of disulphide linkages in keratin, and thus are popularly used for permeation waving. ^{[20, 21]}

Keratolytic Agents

Salicylic acid, urea and guanidine hydrochloride were thought to tertiary structure and possibly secondary linkages (such as hydrogen bonds) in keratin. This agent promotes penetration through the nail. ^{[20, 21]}

Terbinafine

Terbinafine is the most potent drug nowadays for the treatment of onychomycosis. It is an ally amine synthetic antifungal (Fig.3). Terbinafine is fungicidal against dermatophytes and fungistatic against some nondermatophyte molds or yeasts. It inhibits squalene epoxidase. As a result of this inhibition squalene accumulates in the cell and eventually causes cell death.^[22] Terbinafine is commercially available as tablets for systemic treatment of fungal infections counting onychomycosis, but it is also disposable as cream, solution, spray, or gel for the topical treatment of infected skin.^{[23, 24]}

Fig.3 Structural Formula of Terbenafine

IUPAC name: (2E)-N-6, 6-trimethyl-N-(naphthalen-1-ylmethyl)hept-2-en-4-in-1-amine

Treatment of onychomycosis

Oral antifungals are the most effective agents available to treat onychomycosis. Some of the prescribed drugs for oral therapy are griseofulvin, itraconazole, fluconazole, ketoconazole, and terbinafine, of which griseofulvin is not currently used much. However, oral therapy is followed by some disadvantages such as drug interactions, contraindications, side effects, high cost of medication, and a long duration of treatment.

Thus, topical therapies are more desirable, usually recommended for the early stages of the disease, when one or two nails are infected. The Food and Drug Administration (FDA) approved ciclopirox nail lacquer for the treatment of mild to moderate onychomycosis caused by T. rubrum without involvement of the lunula, while ciclopirox and amorolfine have been approved in Europe. ^{[19,
21, 25, 26]}

FACTORS INFLUENCING DRUG DELIVERY THROUGH NAIL

1. Thickness of the nail is a path through which diffusing molecules permeate. The ticker the nail is, the more difficult it will be for the drugs to reach the nail bed.

2. Presence of disease can alter the properties of nail plate, such as nail thickness. Kobayashi et al. ^[27] detected fluxes of 5-fluorouracil through fungal nail plates from eight patients and compared them with fluxes through nail plates from healthy volunteers. They concluded that there is no significant difference and thus the fungal nail permeability can be estimated from the healthy nail permeability data with an exception of very heavy fungal nail plates, where the flux is thought to be higher due to the nail destruction by fungi.

3. Hydration of the nail plate is an important factor which influences drug permeability. With increasing hydration rate of the nail plate, an increase in drug permeability can be observed. ^[28] The fact that water uptake was used as a marker for pre-formulation screening of potential enhancers indicates the importance of the nail swelling on drug permeability.^[29]

4. The dorsal layer of the nail plate is the main barrier to drug permeation process, which was confirmed by Nair et al.^[30] Thus, many techniques have been used in order to remove or damage the dorsal nail layer, not only to influence the main permeability barrier, but in the same time to reduce the thickness of the nail plate. The Path Former device is approved by the Food and Drug Administration (FDA) for controlled nail trephination, i.e. generation of microscopic holes in the nail plate. ^{[31, 32]}

5. Molecular size of diffusing molecule has an inverse relationship with permeation into the nail plate. The smaller the diffusing molecule and the less branched it is, the faster diffusion through the “pores” of the membrane takes place. ^[27]

6. Degree of ionization of diffusing molecule plays an important role in permeation through the human nail plate. The nail permeability of an ionic drug is significantly lower than that of a non-ionic drug. ^[27]

7. Applied formulation can influence drug delivery through the human nail plate from many aspects such as hydration of the nail plate, drug solubility, contact time between formulation and the nail plate, and ability to interact with nail constituents. Aqueous based formulations are suitable for increasing hydration rate of the nail plate which leads to higher permeability of the nail. Therefore, many researchers apply solutions, suspensions, or gels. ^{[9, 32, 33]} In practice, aqueous based formulations are less suitable than lipophilic vehicles due to their easy removal from the nail plate and thus short term contact with the nail surface.

APPROACHES OF NAIL DRUG DELIVERY

a) Topical application

Oral administration of antifungal therapy is inherently associated with GI and systemic side effects. Topical delivery is the most desired therapy due to relatively less severe side effects and better patient compliance particularly in case of pediatric patients. Unfortunately, there are at least two factors that could limit the accumulation and activity of drugs in the nail on topical application. First, the physicochemical properties of the drug need to be favorable for absorption through nail matrix. The nail matrix is reported to be relatively more permeable to polar compounds than non-polar compounds. Second, binding of the drug to keratin reduces the availability of the free drug. Antifungal drugs are reported to possess high binding affinity to keratin.

b) Chemical penetration enhancement

The common approach for enhancing nail drug delivery has been to use keratolytic and thiolytic agents. These agents are known to increase the permeability of nail matrix by chemical modification of keratin. However, their permeability enhancement potential is limited by the factors like penetrability of enhancer and the duration of its presence in the nail matrix might significantly influence the chemical modification of keratin. Topical monotherapy is considered less efficient in treating nail disorders such as onychomycosis due to poor trans‐nail bioavailability of drugs.

c) Physical penetration enhancement

Recently the iontophoretic trans‐nail delivery method showed good results in treating nail fungal syndromes. The effect of iontophoresis on the permeability of salicylic acid across human nail plate was studied using Franz diffusion cell incorporated with electrode.^[34] The results showed drastic increase in the permeability of a test penetrant across nail plate as compared with the conventional method of penetration.

d) Chubtur TM cell

In some special cases the electrophoretic assembly is incorporated with the device. The cell depicted below has the capacity to monitor the permeation and deposition of drug from a formulation when applied topically to a nail in-vitro. Such a system allows the study, development and optimization of perungual delivery systems in an environment close to those that occurs in-vivo.

e) Electro-chemotherapy for nail disorders

The goal of this therapy is to develop an active method of drug delivery across the nail plate which in turn is believed to increase the success rate of topical monotherapy and decrease the duration of treatment of nail disorders. Currently, the electrically mediated techniques for drug delivery across the nail plate are investigated. Recently the iontophoretic trans‐nail delivery method studied. Iontophoresis was found to enhance the transport of drugs across the nail plate significantly. Similar to transdermal iontophoresis, the predominant mechanisms contributing to enhanced transport of drugs in the case of transnail iontophoresis are electrophoresis and electroosmosis. Iontophoretic perm selectivity of the human nail plate and its applicability on the trans‐nail delivery of drugs are also under investigation.

f) Mesoscissioning technology

Mesoscissioning technology creates a micro‐conduit through the skin or nail within a specified depth range. Fully open pathways can be painlessly sized (cut) through the stratum corneum of the skin or through the nail. Micro-conduits, 300‐500 microns in diameter, are produced within seconds and without sensation. In nails, microconduits quickly reduce the painful pressure of subungual hematoma (black toe) and could serve as a prophylactic to prevent such pressure build‐up in runner's nails.

c) Nano patch nail fungus

Nano patch fungus uses AC/DC electrochemistry and targeted drug delivery to actively push antifungal drugs right through the nail cuticle to the actual location of the fungus growth. This would be the first treatment option to directly target nail fungus at its source of growth.

MAJOR CHALLENGES

The nail plate is much thicker creating a much longer diffusional pathway for drug delivery. Additionally, stable disulphide bonds, responsible for the hardness of the nail, are believed to restrict drug penetration. Unlike the skin, the nail plate behaves as a hydrophilic gel membrane and not a lypophilic barrier. ^[35] The chemical and physical differences between the nail plate and the Stratum corneum may thus explain the long treatment times and lack of efficacy of currently available topical formulations.^[36] Therefore, when designing topical formulations for nail drug absorption it is essential to consider the physicochemical properties of the drug molecule (e.g. size, shape, charge log P etc), the formulation characteristics (e.g. vehicle, pH drug concentration), possible interactions between the drug and keratin and possible penetration enhancers.^[37]

REFERENCE:

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2. Baden HP, Goldsmith LA, Fleming B. A comparative study of the physicochemical properties of human keratinized tissues. Biochim Biophys Acta. 322; 1973: 269–278.

3. Zaias N.M.D., Alvarez J. The formation of the primate nails plate. An autoradiographic study in squirrel monkey. J Invest Dermatol. 51(2); Aug 1968: 120-136.

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5. Murdan S. Drug delivery to the nail following topical application. International Journal of Pharmaceutics. 236(1-2); 2002: 1-26.

6. Achten G., Andre J., Laporte M. Nails in light and electron microscopy. Semin. Dermatol. 10(1); March 1991: 54-64.

7. Murdan S. Enhancing the nail permeability of topically applied drugs. Expert Opin Drug Deliv. 5(11); 2008: 1267-1282.

8. Dawber R.P.R., Baran R. Structure, embryology, comparative anatomy and physiology of the nail. In: Baran R., Dawber R.P.R. (Ed.). Diseases of the nails and their management. Blackwell Scientific Publications, Oxford (UK). 1984: pp. 1-23.

9. Kobayashi Y., Miyamoto M., Sugibayashi K., Morimoto Y. Drug permeation through the three layers of the human nail plate. Journal of Pharmacy and Pharmacology. 51(3); 1999: 271-278.

10. Walters K.A., Flynn G.L. Permeability characteristics of the human nail plate. Intrnational J Cosmetic Science 5(6); 1983: 231-246.

11. Baran R. and Dawber R.P.R. Diseases of the nails and their management. Blackwell Scientific Publication, Oxford and Boston. 1994; 2^nd ed: pp. 345-415.

12. Sau P et.al. Bowen’s disease of the nail bed and periungnal area. Arch Dermatol. 130; 1994: 204.

13. Debruyne D. and Coquerel A. Pharmacokinetics of antifungal agents in onychomycoses. Clin Pharmacokinet. 40(6); 2001: 441-472.

14. Drake L.A., Scher R.K., Smith E.B., Faich G.A., Smith S.L., Hong J.J., Stiller M.J. Effect of onychomycosis on quality of life. J Am Acad Dermatol. 38(5); 1998: 702-704.

15. Lubeck D.P. Measuring health-related quality of life in onychomycosis. J Am Acad Dermatol. 38; 1998: 64-68.

16. Ghannoum M.A., Hajjeh R.A., Scher R., Konnikov N., Gupta A.K., Summerbell R., Sullivan S., Daniel R., Krusinski P., Fleckman P., Rich P., Odom R., Aly R., Pariser D., Zaiac M., Rebell G., Lesher J., Gerlach B., Ponce-de-Leon G.F., Ghannoum A., Warner J., Isham N., Elwski B. A large-scale North American study of fungal isolates from nails: the frequency of nychomycosis, fungal distribution, and fungal susceptibility patterns. J Am Acad Dermatol. 43(4); Oct 2000: 641-648.

17. Dawber R.P.R., Baran R. Fungal (onychomycosis) and other infections of the nail apparatus. In: Baran R., Dawber R.P.R. (Ed.). Diseases of the nails and their management. Blackwell Scientific Publications, Oxford (UK). 1984a: pp. 121-156.

18. Lawry M., Rich P. The nail apparatus: a guide for basic and clinical science. Curr. Probl. Dermatol. 11(5); 1999: 161-208.

19. Rodgers P., Bassler M. Treating onychomycosis. Am Fam Physician. 63(4); 2001: 663-672.

20. Gauri M, Joel L., Zatz. Investigation of nail permeation enhancement by chemical modification. J Pharm Sci. 91(2); 2002: 312-323.

21. Soong M.H. Transport properties of drugs and model compounds across the human nail. Ph.D. Dissertation. University of Minnesota. 1991.

22. Larry E. Millikan. Drug Therapy in Dermatology. CRC Press. 2000.

23. De Doncker P. Pharmacokinetics of orally administered antifungals in onychomycosis. Int J Dermatol. 38 (Suppl. 2); 1999: 20-27.

24. Gupta A.K., Ryder J.E. The use of oral antifungal agents to treat onychomycosis. Dermatol Clin. 21(3); 2003: 469-479.

25. Gupta A.K., Tu L.Q. Therapies for onychomycosis: a review. Dermatol Clin. 24(3); 2006: 375-379.

26. Gauwerky K., Borelli C., Korting H.C. Targeting virulence: a new paradigm for antifungals. Drug Discov Today. 14(3-4); 2009: 214-222.

27. Kobayashi Y., Komatsu T., Sumi M., Numajiri M., Miyamoto D., Kobayashi K., Sugibayashi K., Morimoto Y. In vitro permeation of several drugs through the human nail plate: Relationship between physicochemical properties and Nail permeability of drugs. Eur J Pharm Sci. 21; 2004: 471-477.

28. Gunt H.B., Kasting G.B. Effect of hydration on the permeation of ketoconazole through human nail plate in vitro. Eur J Pharm Sci. 32(4-5); 2007: 254-260.

29. Khengar R.H., Jones S.A., Turner R.B., Forbes B., Brown M.B. Nail swelling as a pre-formulation screen for the selection and optimization of ungula penetration enhancers. Pharm Res. 24; 2007: 2207-2212.

30. Nair A.B., Sammeta S.M., Kim H.D., Chakraborty B., Friden P.M., Murthy S.N. Alternation of the diffusional barrier property of the nail leads to greater terbinafine drug loading and permeation. Int J Pharm. 375; 2009: 22-27.

31. Boker A., Burks J. Can a new nail trephination device help treat nail conditions? Pod. Today. 20(11); 2007: 34-36.

32. Malhotra G.G., Zatz J.L. Investigation of nail permeation enhancement by chemical modification using water as a probe. J Pharm Sci. 91 (2); 2001: 312-323.

33. Brown M.B., Khengar R.H., Turner R.B., Forbes B., Traynor M.J., Evans C.R.G., Jones S.A. Overcoming the nail barrier: A systematic investigation of ungula chemical penetration enhancement. Int. J Pharm. 370; 2009: 61-67.

34. Murthy S.N., Waddell D.C., Shivkumar H.N., Balaji A. and Bowers C.P. “Iontophoretic permselective property of human nail”. Journal of Dermatological Science. 46(2); 2007: 150-152.

35. Walters K.A., Flynn G.L. and Marvel J.R. “Physicochemical characterization of the human nail: Solvent effect on the permeation of homologous alcohols”. Journal of Pharmacy and Pharmacology. 37; 1985: 771-775.

36. Mertin D. and Lippold B.C. “In-vitro permeability of human nail and of a keratin membrane from Bovine Hooves: Influence of partition coefficient octanol/water and the water solubility of drugs on their permeability and maximum flux”. Journal of Pharmacy and Pharmacology. 49(9); 1997: 30-34.

37. Kenneth A., Walters, Gordon L., Flynn and John R. Marvel. Physiochemical characterization of the human nail. J Pharm Pharmacol. 35(1); 1983: 28-33.

Received on 12.02.2013 Accepted on 20.03.2013

Res. J. Topical and Cosmetic Sci. 4(1): Jan. –June 2013 page 14-20

S. No.	Name of product	Name of drug	Uses indications	Name of company
1.	Eco-nail, nail lacquer	5% econazole + 18% SEPA nail lacquer	Promotes the release of econazole from dried lacquer film, creating a large chemical gradient at the lacquer nail interface.	Macrochem Corporation, Laxington, MA, United States
2.	Loceryl nail film	5% Amorolfine	SEPA acts as a percutanaeous penetration enhancer which itself has no effect on nail.	Galderma Australia pvt. Ltd., Belrose NSW, Australia
3.	Umecta nail film	Urea (40%), disodium EDTA, glycerin, hydroxyethyl cellulose, PEG-6, Caprylic/Capric glycerides & Xanthan gum	Psoriatic nails, brittle and thick nails.	JSJ Pharmaceuticals, Chrleston, South Carolina, United States
4.	Tazorac 0.1% gel	Tazarotene (0.1%)	Used in the treatment of fingernail psoriasis	Allergan Inc., Irvine, CA, U.S.A.
5.	Zalain nail patch	Sertaconazole nitrate	Once a week nail patch for treatment of onychomicosis and onychodystrophy	Labtec GmbH, Langenfeld, Germany
6.	Penlac nail lacquer	Ciclopirox topical solution	A broad spectrum antifungal medication that also has antibacterial and anti-inflammatory properties	Dermick Laboratories Inc.

Treatment of onychomycosis

5% econazole + 18% SEPA nail lacquer

MAJOR CHALLENGES