NAIL LACQUER AS A TRANSUNGUAL DRUG DELIVERY ...

© 2019 JETIR February 2019, Volume 6, Issue 2 www.jetir.org (ISSN-2349-5162)

JETIR1902625 Journal of Emerging Technologies and Innovative Research (JETIR) www.jetir.org 177

NAIL LACQUER AS A TRANSUNGUAL DRUG

DELIVERY SYSTEM

Akanksha Goja*, Ganesh Kumar Bhatt

Division of Pharmaceutical Sciences ,

Shri Guru Ram Rai University, Dehradun, India

ABSTRACT

Topical therapy is desirable in the treatment of nail disease like onchomycosis which is a nail fungus

causing thickened, ragged, brittle nail. The aim of the current work is to formulate the nail lacquer for the

treatment of disease. The main purpose of the research was to provide a medicament over the nail for the

extended period of time. Topical delivery of medicament over nail is limited due to poor permeability of

drug into nail plate. There are some permeation enhancers which helps in enhancing the permeation. Eg

thioglycolic acid and urea hydrogen peroxide. It works by reducing the disulfide bonds in the nail plate.

Polymers like Carbopol, HPMC, Ethyl cellulose are used and plasticizer like propylene glycol is also used.

Various evaluation parameter are performed for the nail lacquer like PH, drying time, viscosity, smoothness

of flow, gloss respectively.The drug release %age was determined by UV spectrophotometer. FTIR study is

performed which determines the drug and all excipients are compatible.

KEYWORDS - Nail lacquer, Thioglycolic acid, permeation enhancer.

INTRODUCTION[1-3]

Topical delivery of drug is defined as the application of drug to the skin directly containing formulation in

order to treat skin disorders or infections. Topical drug delivery system is better as compared to oral drug

delivery because of less systemic side effects, better adherence and localized action. In topical route, tissue

concentration is higher which is mainly needed for nail or skin infection. The Transungual drug delivery is

the delivery of drug into the nail plate which is keratinized for attaining targeted delivery of drug for treating

nail diseases. Transungual route is responsible for the treatment of fungal infections of nail. Ungual therapy

provides several benefits over oral or systemic route such that preparation is easy compared to oral dosage

form like tablets. Onchomycosis is a fungal infection of the nail mainly caused by moulds, dermatophytes or

yeasts. It mainly results in white or yellow nail discoloration, thickening of nail , nail becomes irregularly

distorted , broken. Medicated nail lacquer given for treating nail diseases leaves an occlusive film after

application which mainly acts as a drug depot from which sustained release of anti fungal is provided for the

entire therapy. It contains drug and film former as a major constituent. The film former which is mainly a

polymer acts as a system for the controlled or sustained release of drug into the nail plate. Due to the

hardness of the nail, many penetration enhancers are used for the delivery of drug into the nail.

ANATOMY AND PHYSIOLOGY OF NAIL[4-6]

A nail is a horn like envelope which covers the tips of fingers and toes and is also a distinctive structure of

the human body. It mainly consists of Nail plate, nail bed, nail matrix, nail folds, Hyponychium,

Paronychium.

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NAIL PLATE

Also known as ‘Body of nail’ or ‘Corpus Unguim’. It is made up of translucent keratin protein composed of

amino acids. It is hard, elastic, translucent and convex in shape and is mainly made up of 25 layers of

flattened, dead, keratinized tightly bound cells. It is produced by a type of modified epidermis. Nail plate is

mainly made up of 3 layers named as Dorsal layer which is the first layer, second one is intermediate layer

and ventral layer is the third layer. Nail plate consists of many elements like copper, Zinc, Iron in small

fractions. Sulphur is mainly responsible for the hardness of the nail plate.

NAIL MATRIX

Also known as matrix unguis, onychostroma is the tissue which is protected by the nail. It mainly contains

nerves, lymph and blood vessels. Nail matrix is a germinative epithelium which is responsible for the

origination of nail. It is responsible for cells production. The superficial portion of the nail plate are mainly

formed by the proximal part of the matrix and the undersurface of the nail is formed by the distal part of the

matrix. Melanocytes are mainly present in lower cell membrane of nail matrix which causes pigmentation of

varying degree on the nail plate depending upon the race.

NAIL BED

Deeper dermis and superficial epidermis are the tissues which are responsible for the composition of nail

bed. Deeper dermis is mainly attached with the bone and is a living tissue while superficial epidermis is

mainly present under the nail plate.

NAIL FOLD

It is mainly divided into proximal and lateral nail fold and nail fold is mainly responsible for the protection

of the nail against harmful agents, irritants, environmental pathogens. It mainly comprises of cuticle and it

directly gets attached to the nail plate.

HYPONYCHIUM[7-9]

It is the epithelium which is present below the nail plate between the junction of skin and free edge of

fingertip. Its function is to form a sealer in order to protect the nail bed from external microorganism.

PARONYCHIUM

It is also called the lateral nail fold which helps in keeping dirt, bacteria away from the nail. It is the soft

tissue which surrounds both fingernails and toenails. It is responsible for the stability of the nail.

DISEASES OF NAIL

When the nail plate starts appearing abnormal due to problems in blood supply, trauma, infection of the nail

plate, it results to the infection of nail. Some of the diseases which are related to nail and its parts are as

follows;

1. Onchomycosis- It is also known as Tinea ungium which is mainly caused due to yeasts [Candida spp.],

moulds[Fussariumspp.] and dermatophytes. It is a fungal infection of the nail in which the nail plate

becomes thickened, irregularly distorted. Symptoms may include white or yellow discoloration of the nail.




TYPES OF ONCHOMYCOSIS[10-11]

1.Distal Subungual onchomycosis

2. Proximal Subungual onchomycosis

3. White superficial onchomycosis

4. Total Dystrophic onchomycosis

Dermatophytes are the most common fungi which is responsible for this disease. Males are most commonly

affected than females. Older people are more frequently affected.

TREATMENT OF ONCHOMYCOSIS[12-15]

The treatment is mainly done by oral antibiotics like itraconazole, fluconazole. Now a days terbinafine is

also used and it is given for 84 days .Topical drug treatment is more effective and Ciclopirox is given for

this disease treatment which is approved by FDA.

PARONYCHIA

It is a nail disease which is caused due to bacteria, fungi or viruses and affects the nail fold part. The

symptoms of this disease are pain, redness, swelling in the nail folds. The infection can start suddenly which

is Acute paronychia or gradually which is Chronic paronychia.




Acute paronychia is mainly caused by bacteria and is often treated with antibiotics. Chronic paronychia is

mainly a yeast infection but can also be traced to bacterial infection.

TREATMENT

Antibiotics such as clindamycin or cephalexin are often used. Clindamycin is more effective in case where

MRSA is common. Drainage is recommended in case of the presence of pus.

PSORIASIS

It is a long lasting auto immune disorder which mainly attacks skin or nails. Cell proliferation may occur in

this disease.50% of people are affected by this disease. Symptoms of this disease are nail plate becomes dry,

pitted and sometimes crumbles may appear. It is a condition in which skin cells build up and form scales,

dry patches. These are different types of psoriasis which are;

1. Plaque Psoriasis- It causes dry, raised, red skin lesions which are covered with silvery scales. It might be

itchy or painful and may occur anywhere on human’s body.

2. Nail psoriasis-It can affect fingernails and toenails causing abnormal nail growth and discoloration.

3. Guttate psoriasis-It mainly affects adults and young children. It is mainly caused by bacteria.

4. Inverse psoriasis- This mainly affects the skin I the armpits, under the breasts and around genitals.

TREATMENT[16-19]

Topical corticosteroids are mainly given because of their high potency. Topical agents like calcipotriol and

tazarotene are also used for the treatment of psoriasis. The most effective treatment which is given is

triamcinolone acetonide is injected into the proximal portion of the nail fold.

Drugs used for nail diseases

There are various factors or organisms which are responsible for nail diseases, out of which some are

harmful and some are not and can be easily cured by taking preventions. Diseases which are harmful can be

cured by some medications and medication therapies are also there to treat these nail diseases. Oral

antifungal drugs are the first choice because the clear the infection more quickly than do topical drugs.

These drugs slowly replace the infected part of the nail.




MEDICATED NAIL LACQUER[20-22]

Formulations containing nail lacquer along with the drug used for the nail delivery of drugs for anti fungal

therapy is called medicated nail lacquer. Previously topical preparations of nail such as nail enamel nail

lacquer and nail varnishes are mostly used for the enhancement of nail beauty and lusture but now

medicated nail lacquers are designed for the treatment of nail diseases. In these medicated nail lacquers,

solvent evaporates after application and leaving a film on the surface of nail. These preparations are

generally used for penetrating antifungal and antimicrobial agents with the help of penetration enhancers

which are used physically, chemically and mechanically. Nail lacquer provides several benefits over oral or

systemic drug delivery such that preparation is easy compared to oral dosage forms like tablets. Drug

interactions and systemic adverse effects are absent. Topical preparations like creams, gels are easily

removed on wipping. Now a days, these formulations are used for the treatment of many nail disorders like

onchomycosis, Psoriasis, Paronychia.

Advantages of nail lacquer

1. Nail lacquer does not get removed on rubbing and wiping but other topical formulations like creams, gels

get removed on rubbing.

2. Targeted drug delivery system.

3. It is used for those substances having poor oral bioavailability.

4. These formulations are having prolonged contact time with the applied surface.

5. There are minimal chances of drug- drug interactions.

Drug for nail

infection

Anti -fungal agents

ALLYLAMINES & BENZYL

AMINE

EG-terbinafine hcl ,

butenafine

azoles

eg-fluconazol

e,

posaconazole,

clotrimazole

Anti -bacterial agents

antipseudomona

ls

eg.panicillin

fluroquinoles

eg -oflozacim,levoflox

CIN

AMINOGLYCOSIDES

EG GENTAMY

CIN,

KANAMYCIN,

NEOMYCIN

POLYENES

EG-AMPHOTE

RICIN-B

NYSTATIN,HAMYCIN

ECHINOCANDINS&HETROCY

LCIC BENZOFU

RANS

EG-GRISEOFULVIN,

ANIDULAFUNGIN,

CASPOFUNGIN




6.The effect of these formulations lasts for longer period because after application the film act as a depot by

which drug gets penetrated via nail in an optimized manner and through sustained diffusion.

Disadvantages of nail lacquer

1. There are some local side effects like periungual erythema and proximal nail fold erythema.

2. Treatment therapy is longer, usually takes 9-12 months for toe nails treatment.

3. Shape change, irritation at the site of application, discoloration of the nail are some of the side effects.

Mechanism of film formation and permeation; [23-25]

The nail lacquer acts as a film forming system which when applied to the nail or skin forms a thin and

transparent film after the solvent gets evaporated. As nail lacquer is directly applied over the nail due to

which the composition of film forming changes because of the loss of volatile composition from the

formulation which is than formed as a film over the surface of nail these formulations gets penetrated

through the nail by breaking disulfide bond of the nail after which there will be the formation of new pores.

good penetration of the drug through nail plate will be beneficial in treating nail disease.

Factors affecting transportation of drug via or through nail plate[26-29]

1.Molecular size of the drug

Molecular size of the drug is inversely proportional to the drug penetration via nail plate. If the size if the

drug is enlarge, diffusion of the molecules get tougher via keratin network of the nail which results in

diminishing the permeability coefficient via nail plate.

2.Hydrophillicity /lipophillicity of the diffusing molecules

Lipid pathway acts as means of permeation of lipophillic molecule. Higher the lipophillicity of the molecule

,higher will be the permeation of molecule across the nail. Nail swelling is responsible for the permeation of

aquous molecules over the nails the nail swells because water works by hydrating the nail and enlarging

better dug penetration

formation of new pores

breakage of disulfide bond

nail lacquer




keratin network which helps in the formation of large pores which intern helps in permeation of diffusing

molecules.

3.Nature of vehicle

Nature of vehicle plays an important role in the transportation of drug via nail plate. Aqueous vehicle is

used which mainly acts by moisturizing the nail which causes the swelling of nail plate which causes

distance between keratin network., then there will be the increase in permeation of large molecules across it.

Use of non polar solvents instead of water leads to decrease in the hydration of the nail when the

formulation is given via nail.

4.Effect of formulation

The formulation also have some effects on the permeation of drug via nail. The ph of the formulation also

creates some effect on the degree of ionization of weak acid and weak base which in turn reduces the

permeation via nail plate which leads in minimizing the solubility in the formulation and when the

formulation is applied over the nail plate it gets splitted which minimizes the interaction of the formulation

with the keratin network of the nail.

Recent advancement in ungual drug delivery system[30-32]

There are few techniques which are recently used for the drug delivery into the nail which are as follows;

Nano patch nail fungus

It helps in targeting the drug directly through the nail cuticle to the location where the fungus is growing. It

targets the drug to the place where its need is maximum.

Electrochemotherapy

In this technique, electric current is used for the delivery of drug directly over the nail plate. It increases the

success therapy and reduces the nail treatment duration which increases patient compliance.

Mesoscissioning technology

It creates micro conduit through skin or nail. In this an open pathway of 300-400 microns diameter is mainly

generated through the nail. In this method, there is the delivery of drug over the membrane in order to treat

nail infection.

Approaches associated with nail drug delivery[34-37]

There are many approaches which are related with nail drug delivery. Physical methods which includes

iontophoresis, etching. Chemical methods which includes keratolytic agents like urea salicylic acid ,organic

solvents .Mechanical methods which include nail abrasion and nail avulsion .

Physical method

It is advantageous as it delivers the hydrophilic and macromolecular substances through the nail plate. some

of which are as follows;




Iontophoresis

Transportation of the substance over a membrane is mainly carried out by using an electric field in respect

of electromotive force. It is mainly considered for the delivery of drug over the keratin network of nail .it is

used for the drug penetration enhancement which is generally for the cure of infection at that site. Now a

days iontophoresis is used for the treatment of herpes simplex ,anesthesia of skin penetration ,of an

antibiotic.

Itching

It occurs due to the chemical exposure of phosphoric acid which can result in the emergence of profuse

microsporosites. These microporosites decreases the contact angle and delivers a surface for bonding

material. after etcing is done on the nail plate a hydrophillic ,sustain release ,drug delivery containing film

former system may be easily delivered.

Laser

In this process a microsurgical lazer apparatus is used with lazer which generally makes holes in the nails.

After that topical drugs like anti fungals and anti bacterial should be directly applied for topical disease

treatment.

UV light

Currently UV light is used in treating onchomychosis disease . In this method nail is heated and then the nail

is exposed to UV light ,this process is usually done in order to treat nail diseases.

Phonophoresis

It is defined as the process in which ultra sound waves are transferred into the tissue surface with the help of

coupling medium . In this process chemical thermal and mechanical alterations in the tissue helps in

describing the increase in the delivery of drug . it mainly results in the improvement in the penetration of

drug via trascellularly as subcutaneously or via cellularly which leads to increase in the pores size of cell

membrane which in turn results in increasing the diffusiblity of drug via a membrane . This methods is used

to increase percuatneous penetration to muscles, nervous and joints and with the help of this technique

increased penetration of anesthetic like amphoterecin-B is generally done.

Chemical method[38-39]

The used substances generally increases the permeability of the drugs by breaking the physical and chemical

bonds of the keratin which induces the stability of nail keratin which results in the nail stability and results

into the passage of drug via nail. Some of the chemical agents which are used for drug penetration are as

follows;

Keratolytic agents [Urea, Salicylic acid]

These keratolytic agents are used to enhance the antifungal penetration of agents like ketoconazole,

miconazole. If these agents are absent, there will be no ungual permeability in a duration of about 60 days.

Organic solvents




Ethanol, propylene glycol, polyethylene glycol are the penetration enhancers which are mainly used as

organic solvents. These helps in increasing the penetration of the agents through nail. These solvents mainly

increases the nail barrier resistivity and mainly manipulates the nail hydration state.

Mechanical method[

It comprises of mainly two methods which are as follows;

Nail abrasion

It is a mechanical method in which there is the penetration enhancement. In this thickness of nail plate is

decreased by standing the nail plate. In this method, sandpaper of no.150 or 180 is used and nail plate

sanding is done on edges for not causing any discomfort. Dentist’s drill is also used as it makes hole in the

nail plate which leads in increasing the topical penetration of drug via nail.

Nail Avulsion

It is further sub divided into two types which are Total nail avulsion and partial nail avulsion.

Nail avulsion is the process in which there is the removal of partial or entire nail plate, which is mainly

affected by microorganisms. In this process, keratolytic agents are used like urea and salicylic acid which

softens the nail and also used in the treatment of disease like onchomycosis which is a fungal infection.

CONCLUSION

The review article aimed at enhancing ungual drug uptake. Transungual drug delivery is better over oral

drug delivery because in trasungual delivery, the drug reaches at the specific site. In this article, we just

concluded that nail lacquer is used for the treatment of nail infections because of its good penetration and

better adherence and when it is applied on the nail surface it leaves a thin film through which drug is

released at the controlled rate to the site of infection. We can say that Nail lacquers are cheap and are

Having better patient compliance than other formulations.

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