Therapeutic and Cosmetic Potential of Nail Lacquers: An Updated Review

Siddhesh Aher, Yash Kodilkar, Kartiki Deshmukh, Sharad Dhotre, Ritesh Deshmukh,

doi:10.5281/zenodo.17799939

Review Paper | Open Access
Volume 03 | Issue 12 | Article Id IJPS/250311541

Therapeutic and Cosmetic Potential of Nail Lacquers: An Updated Review
Siddhesh Aher* Yash Kodilkar Kartiki Deshmukh Sharad Dhotre Ritesh Deshmukh
K. V. N. Naik S. P. Sanstha’s, Institute of Pharmaceutical Education & Research, Canada Corner, Nashik, 422002, Maharashtra, India.

Abstract

Nail lacquers represent an innovative pharmaceutical delivery system for treating nail disorders, combining therapeutic efficacy with cosmetic appeal. The unique microstructure of the nail plate, comprising approximately 80% keratin with distinct lipophilic properties, presents a formidable barrier to conventional topical formulations. Modern medicated nail lacquers overcome this barrier through sophisticated mechanisms including polymer film formation, nail plate hyperhydration, and integration of penetration enhancers such as thioglycolic acid, N-acetylcysteine, and sodium lauryl sulfate. Commercially available formulations including amorolfine 5% (Loceryl®) and ciclopirox 8% (Penlac®) deliver antifungal agents directly to infection sites, avoiding systemic absorption and associated hepatotoxic complications common with oral therapy. Clinical studies demonstrate that nail lacquers achieve cumulative drug release rates exceeding 90% over 24-48 hours, establishing sustained therapeutic concentrations at target tissues. Critically, topical nail lacquer therapy demonstrates markedly superior patient adherence rates (81.8%-85.7%) compared to daily application regimens (59.1%), substantially reducing treatment burden and improving compliance in elderly and immunocompromised populations. Adverse effects remain limited primarily to mild, transient local reactions including periungual erythema and temporary nail discoloration, with documented allergic contact dermatitis being uncommon in pharmaceutical formulations. The favorable safety profile, minimal systemic toxicity, and enhanced patient compliance establish nail lacquers as optimal transungual delivery systems for prolonged therapeutic intervention. This review comprehensively examines nail anatomy, formulation strategies incorporating novel penetration enhancers, mechanism of enhanced drug delivery, clinical efficacy data, and safety outcomes, positioning nail lacquers as superior alternatives to systemic antifungals and conventional topical therapies in managing nail disorders while maintaining excellent cosmetic acceptability.

Keywords

Drug Delivery & Formulation, Nail infections, Penetration Enhancers, Formulation Components, Evaluation & Performance Parameters

Introduction

Nails are transparent protective coverings on the finger tips and toes of feet. They grow out of the cuticle or horny layer of the skin in the cells of the nail matrix. These cells consists of granular layer which possess the power of constantly increasing or growing. The matrix is located within the half-moon or white arc at the base of the nail. This half moon also termed as lunula is not visible on all fingers and toes. The nail does not have a direct blood supply but is connected to blood vessels through the nail bed.Nail lacquers/paint/enamels/varnish are viscous preparations intended to decorate nails of fingers and toes. They can be transparent or coloured, plain or with a glitter, but they all should provide a smooth, impervious film on the nail, without leaving any stains on its surface. Nail lacquers form the largest group of manicure preparations and are distinct from the nail polishes¹.

Historical Development of Nail Lacquers:

Nail coloring dates back millennia, representing one of humanity's oldest cosmetic practices. In ancient China (3000 BCE), royalty developed nail formulas using beeswax, egg whites, gelatin, and natural dyes from orchids and roses, with deep red and gold colors exclusively reserved for nobility as status symbols. Simultaneously, ancient Egypt employed henna-based nail coloring, where darker hues indicated higher social rank—Queen Cleopatra famously wore blood-red nails while lower classes used lighter shades².

The practice persisted through the Ming Dynasty (1368-1644 CE) in China using gum Arabic, egg whites, and beeswax mixtures, subsequently spreading to India and the Middle East via trade routes. Victorian Europe dramatically reversed this trend, favouring natural-looking buffed nails with perfumed oils rather than coloured applications³.

The revolutionary transformation to modern nail lacquers occurred in 1923, driven by automotive paint technology. When the United States seized German chemical patents during World War I, nitrocellulose became commercially available. DuPont's Duco Paint for General Motors featured a glossy, durable nitrocellulose formulation that inspired innovation in cosmetics. French makeup artist Michelle Menard, working for Charles Revson's company, developed the first liquid nail polish by dissolving nitrocellulose in organic solvents—essentially adapting automobile paint technology. This company subsequently rebranded as Revlon in 1932 and revolutionized cosmetic nail applications. Concurrently, Northam Warren commercialized Cutex brand products, introducing colorless liquid nail polish in 1916 and rose-tint formulations in 1917. By the 1950s, Hollywood stars including Marilyn Monroe popularized classic red nail polish globally⁴.

Modern medicated nail lacquers emerged in the 1990s as pharmaceutical innovations. Loceryl (5% amorolfine) launched in 1992, while the FDA approved ciclopirox 8% nail lacquer (Penlac) in December 1999 as the first medicated formulation for treating onychomycosis, marking nail lacquers' transition from purely cosmetic to recognized pharmaceutical delivery systems⁵.

HUMAN NAIL ANATOMY:

The chemical makeup of a nail differs greatly from that of other body parts. It is more likely that the nail is a lipophilic substance. The main lipid content of the nail plate is cholesterol. The fingernail plate is made up of about 25 layers of flattened, dead, and keratinized cells that are thin (between 0.25–0.6 mm), rigid, transparent, and convex in shape. The nail plate is made up of hyponychium, nail substrate, nail bed, and proximate toenail fold, which jointly make up the nail plate. The nail (corpus unguis), formed predominantly by the matrices, emerges via proprioceptive and is held together by lateral fingernail folds. Just at the hyponychium, it is separated from the toenail. A part of the hyponychium known as the "ectodermal band" mirrors the nailstructure's anterior side. This band acts as a barrier against chemical agents and pathogenic organisms, shielding underlying nail tissue from the outer world. Under ordinary circumstances, the nail pack includes 7–12% fluid, but at 100% moisture content, that liquid should exceed 35%. The nail's suppleness and opaqueness depend on its water content. Additionally, it includes relatively little lipids (0.1–1%), with a disulfide linkage content of 10.60%. Keratin (80%), a fibrous protein of nails, protects them from damage and also gives them strength⁶.

Table 1. Diseases and Treatments of the Nails

Disease Name	Causative Organism / Causes	Drugs
Onychia	Bacteria and manifests	Antifungal drugs (e.g. terbinafine, itraconazole, fluconazole)
Onychocryptosis (ingrown toenail)	-	Analgesics (e.g. ibuprofen and acetaminophen), Narcotics
Onychodystrophy	Bacteria, yeast, and dermatophytes	Antifungal drugs
Onychogryphosis	Aspergillus niger	Ciclopirox olamine 8% and efinaconazole 10%
Onycholysis	Dermatophytes and yeast (T. rubrum, C. albicans, scabies)	Antibiotics include tetracyclines, NSAIDs, psoralens, and oral retinoids; Chemotherapeutic agents (e.g. taxanes)
Onychomadesis	Varicella infection, fungal infection	Chemotherapeutic agents, valproic acid, carbamazepine, lithium, and azithromycin
Onychomycosis	Dermatophytes, molds, or yeast	Antifungal drugs (e.g. griseofulvin, terbinafine, itraconazole, ketoconazole)
Onychophosis	Trichophyton rubrum	Keratolytic, local anesthetic
Onychoptosis	-	Intravenous penicillin G for 14 days
Onychorrhexis	Hepatitis C virus	Topical corticosteroid
Paronychia	Candida albicans, Gram-positive & Gram-negative bacteria, herpes simplex virus	Antifungal, antibacterial, and penicillin
Koilonychia	Trichophyton rubrum	Iron supplement
Onychomatricoma	Fungal infection	Oral antifungals
Nail pemphigus	Cutaneous Staphylococcus aureus	Oral corticosteroid (prednisone), corticosteroid cream
Longitudinal erythronychia	Amyloidosis, graft-versus-host disease, hemiplegia, acantholytic epidermolysis bullosa	Chemotherapeutic drugs
Longitudinal melanonychia	Trichophyton rubrum, Candida albicans	Chemotherapeutic drugs (e.g. cyclophosphamide, doxorubicin, taxanes), antimalarial drugs (e.g. quinacrine, chloroquine, mepacrine)
Nail psoriasis	Bacteria (S. aureus, S. pyogenes), viruses (HPV, endogenous retroviruses), fungi (Malassezia, Candida albicans)	Vitamin A derivatives, anti-inflammatory drugs, steroids, immunosuppressive drugs, vitamins

Rationale for Nail Lacquers in Therapy and Cosmetics:

Nail lacquers represent a unique formulation platform serving dual purposes in therapeutic management and cosmetic enhancement.

Therapeutically, medicated nail lacquers constitute innovative transungual drug delivery systems designed to overcome the nail plate's barrier properties. Upon application, volatile solvents evaporate, leaving a thin adherent polymeric film containing active pharmaceutical ingredients that functions as a sustained-release reservoir. Film formation reduces water loss, causing nail plate hyperhydration that increases porosity and facilitates drug diffusion⁷.

Topical nail lacquer therapy offers substantial advantages over systemic antifungals, which require prolonged courses (6-12 weeks), risk hepatotoxicity, and cause drug-drug interactions. Medicated lacquers deliver drugs directly to infection sites, minimizing systemic exposure and adverse events. Commercially available ciclopirox 8% (Penlac®) and amorolfine 5% (Loceryl®) demonstrate clinical efficacy. Recent innovations incorporating penetration enhancers achieve drug release rates exceeding 90% over 24-48 hours. Unlike removable creams, nail lacquers form durable films ensuring sustained drug contact and improved compliance, with combined systemic-lacquer treatment showing superior cure rates (34.6% vs. 22.0%) and completion rates compared to systemic therapy alone⁸.

Cosmetically, nail lacquers serve essential functions impacting quality of life. The nail cosmetics market is expanding from $10.9 billion USD (2021) to $23.1 billion USD (2031). Cosmetic lacquers provide vibrant coloration and protective coating concealing nail abnormalities, representing crucial coping mechanisms reducing stigma and improving self-esteem. Modern formulations incorporate nail strengthening agents, moisturizers, vitamins, minerals, and photoprotective compounds with sun protection factors exceeding 500. The nail lacquer platform uniquely offers advantages including resistance to removal through daily activities, formulation versatility, compatibility with systemic agents, non-invasiveness compared to surgical avulsion, and patient-friendly perception as cosmetic grooming rather than medication⁹.

Mechanism Of Action Of Nail Lacquers:

Drug Release and Transungual Delivery Mechanism:

Nail lacquers operate through a sophisticated mechanism that combines controlled drug release with enhanced transungual drug penetration. The fundamental principle governing drug release from nail lacquers follows Fick's Law of Diffusion, where the rate of drug flux across the nail plate is determined by the diffusion coefficient (D) of the drug within the polymer film and the concentration gradient (dc/dx) established across the diffusion pathway¹⁰:

J=Ddcdx

Upon application to the nail surface, volatile organic solvents in the lacquer formulation rapidly evaporate—typically within 30-60 minutes—leaving behind a thin, transparent, colorless polymer film containing the dissolved or dispersed active pharmaceutical ingredient. This film formation is critical to the delivery mechanism. As the solvent evaporates, drug concentration within the remaining polymer matrix increases substantially; the drug concentration in the final film can reach 12% or higher compared to the original lacquer solution. This concentration gradient creates a driving force for sustained drug diffusion from the film into the underlying nail structure over extended periods¹¹.?

Enhancement Through Nail Hyperhydration

The polymer film adhering to the nail surface creates a critical microenvironment by reducing transepidermal water loss from the nail into the atmosphere, causing hyperhydration of the upper nail plate layers. This hydration effect represents a pivotal mechanism in enhancing drug penetration because water functions as a natural plasticizer and permeation enhancer. Increased nail hydration enlarges the spaces between keratin fibers, effectively increasing nail porosity and reducing the barrier resistance imposed by the compact keratinized nail structure¹².

Penetration Enhancers and Barrier Modification

To overcome the nail plate's formidable barrier properties, medicated nail lacquers incorporate chemical penetration enhancers that modify nail microstructure and improve drug diffusion. Sodium lauryl sulfate (SLS) at 1% w/w concentration demonstrates superior enhancement capability, reducing the contact angle between lacquer solutions and the nail surface from approximately 69° (water alone) to 30.7°, thereby dramatically improving spreading and penetration. This enhanced wetting creates random porous microstructures within the nail plate that reduce diffusional barriers¹³.

Active Ingredient Physicochemical Properties:

Drug penetration through the nail plate depends critically on molecular size, hydrophilicity, and lipophilicity of the active ingredient. The nail plate functions as a molecular sieve comprising keratin strands with fixed inter-strand spacing; smaller molecular weight drugs penetrate more readily than larger molecules. Optimal drug candidates exhibit moderate hydrophobic character—hydrophobic substances encounter rate-limiting steps when penetrating lipid-rich domains within the nail, while fully hydrophilic molecules struggle to penetrate lipophilic barriers¹⁴.

Sustained Release and Clinical Efficacy:

Optimized nail lacquer formulations achieve cumulative drug release rates exceeding 90% over 24-48 hours, with some formulations sustaining therapeutic release for 48 hours or longer. This prolonged release ensures continuous therapeutic drug concentrations at the nail infection site while maintaining patient compliance through reduced application frequency (typically once or twice weekly versus daily dosing for creams). The matrix-type controlled release mechanism, combined with nail hyperhydration and penetration enhancement, positions nail lacquers as superior transungual delivery systems compared to conventional topical formulations.¹⁵?

Formulation Aspects:

Key Components:

1.Film Former:

The primary film former used in nail lacquers is nitrocellulose, commonly available in SS grades (10.7–11.2% nitrogen) and RS grades (11.2–12.8% nitrogen) with viscosities of ¼ sec, ½ sec, and 4–5 sec. Nitrocellulose provides hardness while maintaining flexibility and ensures good adhesion to the nail surface, thereby reducing chipping and peeling. It imparts excellent gloss, which is highly preferred by consumers, and allows weak retention of volatile solvents. Additionally, it provides transparency to the enamel and is not completely occlusive to water or air, helping prevent fungal infections. Alternative film formers include cellulose acetate isobutyrate, polyvinyl acetate and nitrocellulose blends, ethylcellulose and nitrocellulose blends, and acrylates and cellulose acetates, which serve to modify gloss, adhesion, and film strength.

Boiling Point: 83°C | Melting Point: 100°C

Decomposition Temperature: > 180°C

Nitrocellulose is highly flammable; the b.p. of 83°C represents the vaporization point of the liquid form. Melting point of 100°C indicates the transition from solid to semi-liquid state. Decomposition begins at temperatures exceeding 180°C. Stored in dampened form with isopropyl or ethyl alcohol for safety.

2. Resins:

Resins are used to enhance the hardness, gloss, and adhesion of nail lacquers. Natural resins such as shellac, benzoin, dammar, sandarac, and ester gums provide gloss and reduce nitrocellulose shrinkage. Modern resins, primarily polyaryl sulphonamides, such as Santolite MS 80 (which imparts flexibility and high gloss) and Santolite MHP (which provides a harder film), are formed by condensing aryl sulphonamide and formaldehyde at 110°C in equimolecular proportions, yielding a colorless resin. These resins are used at concentrations of 5–10% in formulations to improve gloss, adhesion, and hardness. Alternative resins include polyester resins (less allergenic than sulphonamides), oil-free alkyl resins, acrylate resins, vinyl resins (especially polyvinyl alcohol), and small amounts of polystyrene or nylon, which enhance wear resistance, flexibility, and toughness¹.

Table 2: Physicochemical Properties and Functional Roles of Resins

Component	Boiling Point	Melting Point	Role
Polyaryl Sulphonamide Resin	110°C (condensation temp)	Amorphous (not applicable)	Predominant resin; heated to 110°C during synthesis
Polyester Resin	Non-volatile	High Tg (~80-100°C)	Modern alternative; lower allergenicity
Acrylate Resins	Non-volatile	Amorphous	Excellent wear resistance; high Tg
Polyvinyl alcohol/Polyvinyl acetate-butyrate	Non-volatile	Amorphous	Improves adhesion and flexibility

3. Plasticizers:

Plasticizers are added to reduce film hardness and increase flexibility. Common examples include dibutyl phthalate (DBP), tributyl phthalate (TBP), n-butyl stearate, resorcinol diacetate, castor oil, triethyl citrate, tributyl citrate, triphenyl phosphate, tricresyl phosphate, benzyl benzoate, and solid camphor. Typically used at 5% of the total mixture or 25–30% of film formers, plasticizers prevent brittleness and cracking, improve adhesion and durability, influence gloss, and speed up solvent evaporation.

Table 3: Physicochemical Properties and Functional Roles of Plasticizers

Component	Boiling Point	Melting Point	Role
Dibutyl phthalate (DBP)	Slightly volatile	~78°C	Most common; reduces hardness; 5% w/w
Tributyl phthalate (TBP)	Slightly volatile	~78°C	Similar to DBP
N-Butyl stearate	High b.p. (non-volatile)	~50°C	Reduces brittleness
Camphor	Sublimes at 178°C	~178°C	Solid form; volatile above melting point; 4.5% w/w
Triethyl citrate	High b.p. (non-volatile)	Liquid	Improves flexibility
Tributyl citrate	High b.p. (non-volatile)	Liquid	Enhances durability
Benzyl benzoate	~201°C	Liquid	High boiling; excellent flexibility
Resorcinol diacetate	Non-volatile	Moderate	Flexibility and gloss

4. Solvents (Active Solvents):

Solvents dissolve and disperse the film formers, resins, and other components, producing a homogeneous and viscous preparation. They influence drying time, brushability, and film characteristics. Common solvents include esters such as n-butyl acetate (boiling point 110–130°C), ethyl acetate (75–83°C), and amyl acetate (120–150°C). Ketones are often used with esters, and alcohol mixtures are preferred for SS-grade nitrocellulose¹.

Table 4: Physicochemical Properties and Functional Roles of Solvents

Component	Boiling Point	Melting Point	Role
Ethyl acetate	75–83°C	Liquid	Primary active solvent; low boiling point ensures quick drying
N-Butyl acetate	110–130°C	Liquid	Medium boiling point solvent; balances evaporation rate
Amyl acetate	120–150°C	Liquid	High boiling point solvent; slower evaporation for better film formation

5. Couplers (Latent Solvents):

Couplers such as isopropyl alcohol (b.p. 82°C) and ethyl alcohol are added to increase the solvent strength when used with active solvents. They act as humectants and moisteners, improving miscibility of ingredients. When used up to 40–50%, they enhance the overall uniformity of the formulation.

Table 5: Physicochemical Properties and Functional Roles of Couplers

Component	Boiling Point	Melting Point	Role
Isopropyl alcohol	82°C	Liquid	Acts as humectant and coupler (40–50% addition possible)
Ethyl alcohol	78–79°C	Liquid	Coupler; used as dampening agent for safety

6. Diluents:

Diluents are used to adjust viscosity and reduce cost. Common examples include aromatic hydrocarbons such as toluene (b.p. 111°C) and xylene (b.p. 143°C), as well as aliphatic hydrocarbons like hexane and heptane, and naphthas. Diluents must evaporate faster than solvents to prevent nitrocellulose precipitation and maintain a smooth film. They also help stabilize viscosity and minimize the impact of multiple lacquer layers¹.

Boiling Point Range: 68–143°C

Table 6: Physicochemical Properties and Functional Roles of Diluents

Component	Boiling Point	Melting Point	Role
Hexane (Aliphatic)	68–69°C	Liquid	Low boiling point diluent; reduces cost
Heptane (Aliphatic)	98–99°C	Liquid	Medium boiling point diluent
Toluene (Aromatic)	111°C	Liquid	Standard aromatic diluent; b.p. 111°C
Xylene (Aromatic)	143°C	Liquid	High boiling point aromatic diluent
Naphthas	Variable	Liquid	Mixed hydrocarbons; variable boiling range

7. Opacifying Agents:

Opacifying agents such as titanium dioxide (the preferred whitening agent) and zinc oxide are added to provide opacity and color coverage. They ensure that the shade on the nail matches the color seen in the bottle and help mask the natural nail tone.

Table 7: Physicochemical Properties and Functional Roles of Opacifiers

Component	Boiling Point	Melting Point	Role
Titanium dioxide	Not volatile	~1843°C	Primary whitening/opacifying agent
Zinc oxide	Not volatile	~1973°C	Secondary opacifier
Iron oxides (Red, Yellow, Black)	Not volatile	>1000°C	Colorants
Iron Blue, Ultramarine	Not volatile	>1500°C	Colorants
Chrome oxide green	Not volatile	>2000°C	Green colorant

8. Colorants:

Colorants give nail lacquers their desired shade. Certified colorants (FD&C and D&C approved) include red iron oxide, yellow iron oxide, iron blue, iron black, ultramarine blue, and chrome oxide green. Earlier dyes like eosin, carmosine, and rhodamines were abandoned due to staining. Modern colorants are designed to provide light resistance and remain stable against detergents and pH changes, ensuring even coverage for delicate shades¹.

9. Pearlescent Agents:

Pearlescent agents impart brilliance and decorative effects. Guanine (2-amino-6-hydroxy purine), derived from fish scales, produces natural shimmer but is expensive. Economical alternatives include bismuth oxychloride (BiOCl), which provides a mirror-like effect, and titanium dioxide-coated micas, which yield a softer luster. Metallic powders like silver and aluminium are also used for frosted finishes and added brilliance.

Table 8: Physicochemical Properties and Functional Roles of Pearlescent Agent

Component	Boiling Point	Melting Point	Role
Guanine (from fish scales)	Not volatile	Not applicable (protein)	Natural pearl essence; produces luster
Bismuth oxychloride (BiOCl)	Not volatile	Not applicable (crystalline)	Mirror-like effect; more economical
Titanium dioxide-coated micas	Not volatile	>1000°C	Softer luster effect
Silver and Aluminum powders	Not volatile	Not applicable (metals)	Pearl effects

10. Suspending Agents (Gellants):

Suspending agents, such as cation-modified montmorillonites (e.g., bentonite and stearalkonium hectorite), stabilize non-setting enamels and prevent pigment settling. They are activated using organic or inorganic acids to promote clay swelling. These agents increase thixotropy, allowing the lacquer to flow easily under shearing and regain thickness at rest¹.

11. UV Absorbers:

To enhance product stability, UV absorbers like benzophenones and their derivatives are added. They protect bismuth oxychloride from light degradation, prevent nitrocellulose from UV damage, and maintain color stability by shielding pigments from fading¹.

EXAMPLE FORMULATIONS:

Composition of Different Nail Lacquer Formulations:

Component	Creamy Enamel (%)	Transparent Lacquer (%)	Pearlescent (%)	Base Coat (%)	Top Coat (%)
Nitrocellulose RS/1/2 sec	10	15	14.90	10	16
Ethyl acetate	50	-	-	34	10
Butyl acetate	20	29.35	34.04	-	10
Diethyl/Dibutyl phthalate	15	3.75	4.8	2	5
Toluene	-	6.40	30.00	39	45
Camphor	4.5	-	2.4	-	-
Isopropyl alcohol	-	1.10	-	5	10
Santolite resin	-	-	7.10	10	4
Toluene sulphonamide formaldehyde	-	-	-	-	-

Penetration Enhancers In Nail Lacquers:

Nail lacquers represent an innovative topical delivery system for treating nail disorders such as onychomycosis. However, the dense, keratinized structure of the nail plate poses a significant barrier to drug penetration. Penetration enhancers have emerged as critical formulation components to facilitate transungual drug delivery and improve therapeutic efficacy.

Thioglycolic Acid and Reducing Agents:

Thioglycolic acid (TGA) is among the most extensively investigated penetration enhancers for nail lacquers. As a reducing agent, TGA disrupts the disulfide bonds (-S-S-) in the alpha-keratin network of the nail plate, creating pores that facilitate drug transport through the nail barrier. Studies have demonstrated that TGA increases drug flux by approximately 2-4 fold and can enhance penetration of compounds such as ciclopirox olamine and terbinafine. When applied at concentrations between 2.5-10% w/v, TGA provides optimal enhancement without causing excessive nail softening. The mechanism involves free radical generation at lower thiolate ion concentrations, which specifically disrupts keratin structure. TGA has shown particular efficacy when combined with other enhancers; sequential application of TGA followed by urea hydrogen peroxide dramatically increased terbinafine flux by approximately 19-fold¹⁷.

Polyols and Plasticizers:

Polyethylene glycol 400 (PEG 400) serves dual roles as both a plasticizer and penetration enhancer in nail lacquer formulations. By promoting nail hydration and swelling, PEG 400 enlarges the spaces between keratin fibers, enabling molecules to diffuse more readily through the nail plate. PEG 400 is typically incorporated at concentrations of 2-10% v/v and improves film flexibility while maintaining adhesion properties. Glycerol, another polyol, functions similarly, enhancing hydration-mediated drug penetration. These polyols work through aqueous pathway mechanisms, fundamental to ungual drug permeation¹⁸.

Amino Acids and Thiol Compounds:

N-acetylcysteine and carbocysteine represent important amino acid-based penetration enhancers that contain free thiol groups (-SH). These compounds cleave disulfide bonds in nail keratin, similar to TGA but through different redox mechanisms. Studies comparing enhancers demonstrated that N-acetylcysteine at 5% w/v provided hydration enhancement factors comparable to TGA and 2-mercaptoethanol. These compounds also exhibit antifungal properties, providing synergistic benefits in antifungal nail lacquer formulations.

Surfactants and Other Agents:

Sodium lauryl sulfate (SLS) functions as an anionic surfactant penetration enhancer, promoting nail penetration through alterations in nail microstructure and reduction of contact angle between lacquer and nail surface. At 3-5% w/v concentration, SLS significantly improves spreading and permeation of active agents. Other enhancers including menthol, keratolytic agents (salicylic acid, urea), and lactic acid contribute through complementary mechanisms—from hydration effects to pH modulation and keratin disruption¹⁹.?

Method Of Preparation Of Nail Lacquer:

The method used to formulate medicated nail lacquer is a simple mixing method. In the first step, the polymer is added slowly into the volatile solvent and makes a homogeneous mixture by using a magnetic stirrer at a constant speed. In the second step the drug is mixed with solvent and plasticizer by continuous stirring²⁰. Then, the homogenous mixture obtained from step second is added slowly into the step first mixture. To the above homogenous clear solution permeation enhancers (thioglycolic acid, 2-mercaptoethanol, and urea), the solution is then added with coloring agents if required, and volume is made up to the desired volume by adding solvent²¹.

Evaluation Of Nail Lacquer:

Non-volatile content:

On an 8 cm in diameter glass petri plate, 1gm of the material was taken. Tared wire was used to disseminate the sample equally. The dish was baked for 1 hour at 105 degrees Celsius, and then it was taken out, allowed to cool, and weighed. The variation in sample weight once drying was established.

Smoothness of flow :

The sample was spread out on a glass plate and poured to a height of about 1.5 inches.

Water resistance :

This is a measurement of the film's water-permeability resistance. This was accomplished by coating a surface with a continuous film and submerging it in water. An increase in weight was observed following immersion, which made the water appear deeper. Resistance.

Drug content:

World Journal of Pharmaceutical Research By precisely dissolving 1ml of nail lacquer in methanol, the drug concentration of the lacquer was ascertained. Using a UV-visible spectrophotometer (UV- 1700, Shimadzu, Japan) at 260 nm, absorbance was measured the appropriate dilution.

Colour/Shade Assessment:

Each batch is visually compared with a pre-approved master colour standard and verified using instrumental colorimetry for precision. Colour must match consistently across batches, bottles, and on actual nail application. Any deviation or off-shade results in batch rejection, as colour consistency is vital for brand identity and consumer appeal.

Viscosity (Fluid Flow and Application Properties):

Viscosity is assessed using a Ford Cup or Brookfield Viscometer to evaluate flow characteristics. Ideal viscosity lies between 100–160 cps for standard lacquers. Proper viscosity ensures smooth application, uniform drying, and stable film formation—critical for overall performance.

Gloss/Shine (Luminance and Reflectance):

Gloss is measured visually or instrumentally using a gloss meter at a 60° angle. A reading above 80 gloss units is acceptable, while 85–95 GU is ideal. High gloss reflects proper resin-plasticizer balance and is a major consumer preference indicator.

Drying Time:

A 0.006-inch film is applied and monitored for “dry-to-touch” and complete set times. Drying within 5 minutes and full handling within 30 minutes is considered ideal. Fast-drying formulas cater to consumer convenience and practicality.

Film Hardness (Scratch Resistance):

After standardized drying, films are tested via thumbnail or microhardness methods. Resistance to scratching indicates good resin-plasticizer balance and ensures long-lasting, durable finishes.

Safety, Compliance, And Patient Outcomes In Nail Lacquer Drug Delivery:

Nail lacquer formulations represent a significant advancement in transungual drug delivery, offering distinct advantages for minimizing systemic toxicity while enhancing patient adherence and clinical outcomes. Topical nail lacquer therapy fundamentally differs from systemic antifungal administration by delivering therapeutic agents directly to the site of infection, thereby substantially reducing systemic side effects and avoiding first-pass metabolism. This localized approach ensures that drug concentrations remain therapeutically active at the target tissue while minimizing absorption into systemic circulation, consequently reducing the risk of drug-drug interactions and hepatic complications commonly associated with oral antifungal therapy²².

Oral antifungal treatments, particularly terbinafine and itraconazole, carry considerable systemic adverse effects that compromise patient compliance, with reported discontinuation rates exceeding 19% due to adverse reactions and 1.5% specifically attributable to hepatotoxicity. In contrast, clinical studies demonstrate that nail lacquers are associated with minimal to no systemic side effects, with reported adverse events limited primarily to local reactions at the application site. When adverse effects occur with topical nail lacquers, they are typically mild and transient, including periungual erythema, transient burning sensations, and temporary nail discoloration, which resolve upon treatment discontinuation or appropriate application technique adjustment²³.

Patient adherence represents a critical determinant of treatment success in onychomycosis management due to the prolonged therapy duration required for nail plate turnover. Once-weekly amorolfine 5% nail lacquer demonstrates superior adherence rates compared to daily application regimens, with studies reporting 85% adherence to amorolfine versus 60% adherence to daily ciclopirox applications. This improved compliance translates directly into enhanced clinical efficacy, as demonstrated in randomized clinical studies where adherence rates of 81.8%-85.7% were achieved with amorolfine, substantially higher than the 59.1% adherence to daily urea/bifonazole combination therapy. The convenience of once-weekly application substantially reduces the burden of treatment, particularly for elderly and immunocompromised populations²⁴.?

Regarding allergic reactions and adverse effects, nail lacquers present a favorable safety profile compared to conventional nail cosmetics or systemic therapies. Local adverse effects are generally mild and typically manifest only when products are inadvertently applied to periungual skin rather than the nail plate. Documented allergic contact dermatitis associated with nail lacquer components is uncommon and primarily involves specific resin components or formaldehyde in cosmetic nail polishes rather than pharmaceutical formulations. When sensitization occurs, it manifests as contact dermatitis at the application site and discontinuation resolves symptoms²⁵.

SUMMARY:

Nail lacquers represent a transformative advancement in transungual drug delivery, uniquely bridging pharmaceutical efficacy with cosmetic acceptability. The nail plate, comprising approximately 80% keratin with lipophilic properties and a compact microstructure spanning 0.25-0.6 mm across 25 layers, has traditionally posed a formidable barrier to topical drug penetration. Modern medicated nail lacquers overcome this challenge through sophisticated formulation strategies integrating polymer film formation, nail hyperhydration mechanisms, and chemical penetration enhancers including thioglycolic acid, N-acetylcysteine, sodium lauryl sulfate, and keratolytic agents.

Pharmacologically, commercially available formulations such as amorolfine 5% (Loceryl®) and ciclopirox 8% (Penlac®) deliver antifungal agents directly to infection sites with cumulative drug release rates exceeding 90% over 24-48 hours. This sustained-release mechanism, combined with reduced systemic absorption compared to oral therapies, substantially minimizes hepatotoxic complications and drug-drug interactions that compromise patient outcomes with systemic antifungals. The formulation architecture, comprising nitrocellulose film formers, polyaryl sulphonamide resins, plasticizers, and volatile organic solvents, creates an impervious, durable coating ensuring prolonged drug contact with infected nail tissue.

Patient adherence emerges as a critical determinant of treatment success. Once-weekly amorolfine applications demonstrate adherence rates of 81.8%-85.7%, substantially exceeding 59.1% adherence to daily topical regimens and 45% overall compliance with oral medications. This superior compliance directly translates into enhanced clinical efficacy, with combined systemic-lacquer therapy achieving cure rates of 34.6% versus 22.0% with systemic therapy alone. The reduced application burden particularly benefits elderly and immunocompromised populations vulnerable to onychomycosis.

CONCLUSION:

Medicated nail lacquers represent a transformative advancement in transungual drug delivery, successfully addressing the nail plate's formidable keratin barrier through sophisticated formulation strategies integrating penetration enhancers, polymer films, and hyperhydration mechanisms. Commercially available formulations including amorolfine 5% (Loceryl®) and ciclopirox 8% (Penlac®) achieve cumulative drug release exceeding 90% over 24-48 hours while minimizing systemic absorption and hepatotoxic complications inherent to oral antifungals. Superior patient adherence rates of 81.8%-85.7% with once-weekly applications substantially exceed oral medication compliance, directly translating into enhanced clinical efficacy with combined systemic-lacquer therapy achieving 34.6% cure rates versus 22.0% with systemic therapy alone. The exceptional safety profile, characterized by minimal systemic side effects and mild, transient local adverse reactions, coupled with dual therapeutic and cosmetic benefits, establishes nail lacquers as optimal pharmaceutical platforms for managing nail disorders. These formulations exemplify successful integration of pharmaceutical innovation, patient-centered design, and clinical efficacy, solidifying their role as preferred therapeutics for onychomycosis and other nail pathologies while maintaining cosmetic acceptability essential for long-term treatment adherence and improved patient quality of life.

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