Formulation And Evaluation of Herbal Nail Lacquer for Treatment of Onychomycosis

Over the last decades the treatment of illness has been accomplished by Administrating drugs to human body via various routes namely oral, parental, topical, Inhalation etc. Every medical condition demands an accurate and appropriate treatment. As a matter of fact, the thought of resolving the patient’s disease with least harm done To the patient’s health is said to be the basic goal of any therapy. Moreover a good Treatment technique necessitates thorough knowledge of pharmacokinetics and Pharmacodynamics of the intended drug. Hence we struggle day to day relentlessly to Research and better our techniques and technology to develop with the best mode of Treatment ensuring fast recovery as well as assuring safety of the patient. Human nails do not have only protective and decorative role, but can Also be considered as an alternative pathway for drug delivery, especially in nail Diseases such as onychomycosis or psoriasis. These nail diseases are widely spread in The population, particularly among elderly and immune-compromised patients. Although the architecture and composition of the nail plate severely limits penetration Of drugs and in addition to that only a fraction of topical drug penetrates across the nail, Oral therapies are accompanied by systemic side effects and drug interactions. For the Successful treatment of nail disease the applied active drug must permeate through the Dense keratinized nail plate and reach deeper layers, the nail bed and the nail matrix  [1] Major challenges of drug delivery to the nail (ungual drug delivery), with the lack of Understanding of both the barrier properties of the nail and formulations to achieve Enhanced ungual delivery restricting the efficiency of topical treatments for nail Disorders. And also suffer from low patient compliance due to the long treatment Periods (up to 4?8 months) which are required. However, existing oral formulations typically contain large doses of Active ingredients and also require long treatment, creating the potential for systemic Toxicity especially in the liver. Thus, developing more effective methods for nail drug Delivery is an important objective for the pharmaceutical industry.[2]

Structure of human nail

The chemical composition of the human nail severely differs from other body membranes. The plate, composed of keratin molecules with many disulphide linkages and low associated lipid levels, does not resemble any other body membrane in its barrier properties – it tends more like a hydrogel than lipophilic membrane.[3]

fig no 1:  structure of human nail

The human nail consists of

o Nail matrix or the root of the nail

o Nail bed

o Eponychium or cuticle

o Paronychium

o Hyponychium

o Nail plate.

[4,5]

Functions of nail:

• A healthy nail protects the distal phalanx, the finger tip, and the surrounding tissues from the injuries.
• It helps to enhance delicate movements of the distal digits through counter pressure exerted on the pulp of the finger.
• The nail acts as a counterforce when the end of the finger touches an object and hence enhancing the sensitivity of the fingertip.
• Without nails on the fingertips, it is not possible to grab and hold the things accurately or precisely. (6-7)

Onychomycosis

Onychomycosis is a fungal infection of the nail unit. When dermatophytes cause onychomycosis, this condition is called tinea unguium. The term onychomycosis encompasses the dermatophytes, yeasts, and saprophytic mold infections. An abnormal nail not caused by a fungal infection is a dystrophic nail. Onychomycosis can infect both fingernails and toenails, but onychomycosis of the toenail is much more prevalent.

Fig no 2: Structure of onychomycosis

1.5 Classification of Onychomycosis

Fig no 3: type of onychomycosis

1. Distal subungual onychomycosis

The most common form of Tinea unguium is distal subungual. Distal subungual onychomycosis may develop in the toenails, fingernails or both. The infection is usuallycaused by Trichophytonrubrum, which invades the nail bed and the underside of the nailplate, beginning at the hyponychium and then migrating proximally through the underlying nail matrix. Susceptibility to distal superficial onychomycosis may occur in an autosomal dominant pattern within families.

2. White superficial onychomycosis

White superfici C. Proximal subungual onychomycosis Proximal subungual onychomycosis occurs when the infecting organism, usually T. rubrum, invades the nail unit through the proximal nail fold, penetrates the newly formed nail plate and then migrates distally. Fingernails and toenails are equally affected. This form of onychomycosis usually occurs in immune compromised persons and is considered a clinical marker of human immunodeficiency virus infection.

3. Candida onychomycosis

Candida onychomycosis can be divided into three general categories. Infection beginning as a paronychia (also called a “whitlow”), the most common type of Candida onychomycosis.

4. Total dystrophic onychomycosis

Total dystrophic onychomycosis may be the end result of any of the four main forms of onychomycosis.[8,9]

Diagnosis of Onychomycosis

Conventional methods for identifying fungal organisms in the nail plate of patients with onychomycosis (OM) include direct microscopy (after potassium hydroxide solution incubation), fungal culture, and histopathology (using Periodic Acid Schiff [PAS] stain). Surgical pathology testing (of the subungual nail bed and/or the nail plate) using PAS stain is the current gold standard (approaching 100% sensitivity) for the diagnosis of OM. Newer methods for diagnosing OM include polymerase chain reaction (which has a very high specificity), optical coherence tomography, confocal laser scan microscopy, matrix- assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), and phase contrast hard x-ray microscopy. Confirmation of observations and availability and cost must be considered before these newer methods for diagnosing OM can be incorporated in clinical practice. [10,11,12]

Treatments of Onychomycosis

Onychomycosis is a term that encompasses all the nail pathologies caused by fungi and accounts for approximately 50% of all nail diseases [13]. The treatment of onychomycosis is a challenging task to patients and professionals as the infection is embedded within the nail. It may take a year or more to get cure as new nail growth must completely replace the old and infected one. Also because of the difficulty in attaining a definitive cure and the high recurrence rate. Patients greater than 55 years of age may have a higher rate of relapse.

•Oral therapy

• Topical therapy [ 14,15,16]

Nail Lacquer

Topical nail preparations like lacquers, varnishes, enamels etc. are generally used to enhance beauty of nails, imparting color and luster to nail. But in recent times medicated lacquers are specially designed for the nail. These preparations are generally used in fungal diseases. Use of this system avoids oral toxicity of anti-fungal drugs.[17] Medicated nail lacquers are the formulations that have maximal antifungal efficacy as a transungual drug delivery system. After application, the solvent from the lacquer formulation evaporates leaving an occlusive film on which the drug concentration is higher than in the original formulation. This increases the diffusion gradient and permeation through dense keratinized nail plate.[18]

• Advantages

1. It cannot be easily removed by rubbing or washing.

2. In addition, the effect is long lasting; single application of lacquer provides protection for one week.

3. Preparation is easy as compared to oral dosage form.

4. Minimal or no systemic side effects.

• Disadvantages

1 Rashes relate to adverse effects such as periungual erythema and erythema of the proximal nail fold were reported most frequently.

2 Other adverse effects which were thought to be casually related include nail disorder such as shape change, irritation, ingrown toe nail and discoloration.[19]

MATERIALS AND METHODS

Materials:  Tea tree oil, ethyl cellulose, Ethyl acetate, salicylic acid, pottacium hydrogen phthalate and Castor oil.

METHOD:

Preparation of nail lacquer

The formulation trail is were done as per formula given in table no 4. The medicated nail lacquer was prepared by simple mixing method .  The film forming polymer ethyl cellulose was dissolved in ethyl acetate using stirring. The polymer was allowed to dissolved completely, then plasticizer (dibutyl phthalate)  was added to the solution while stirring [20]. Castor oil and tea tree oil were added into the polymer solution. Further, salicylic acid and glycerin were added in the desired amount and mixed properly using magnetic stirrer. The formulation was then filled in the narrow mouth containers and sealed with liner and cap. The developed nail lacquer was further optimized to arrive at the final formulation containing desired levels of film former and release retardant

Table no: 1 formulation of nail lacquer

fig no : 4 formulation of nail lacquer

Evaluation test

1. Physical appearance

Visual observations were made of the formulations' color, transparency, and application characteristics.

2. Drying time:

The drying time is the primary test used for the nail lacquer. Briefly a brush applicator was used to spread the lacquer on a 2 cmArea on a glass slide at room temperature and let to dry. After every 15 sec, a gloved finger was used to touch the film. The time required To obtain dry to touch condition was recorded [21].

3. Smoothness to flow:

The sample was spread on the glass slide. The glass slide was Then raised vertically [22].

4. Gloss:

The sample covered the nail in an even layer. The gloss and the Marketed cosmetic nail lacquer were visually compared.

5. Non- volatile content:

A glass petri plate was used for the sample measurement, and the  weight was recorded. The plate was then heated for one hour at 105C. After an hour, the plate’s weight was recorded. The difference Between initial and final weight was calculated. The percentage non-Volatile content was determined by formula:

% non -volatile content = initial weight - final weight/ initial weight ×100

6. Water resistance test:

A glass plate was used to apply the sample. After being weighed, The glass plate containing the fully dried sample was submerged in Water. The sample was examined visually for discoloration, turbidity, Blistering, and weight change.

RESULT AND DISCUSSION

The objective of the present study was to formulate a nail lacquer for preventing fungal growth on toe nails or finger nails so that the appearance of the nails is improved. Hence utilizing Tea tree oil and castor oil as anti- inflammatory and anti-fungal a medicated nail lacquer is formulated to provide the requisite sustained medication release, better drug permeation, and desirable anti-fungal effectiveness. The prepared formulation included salicylic acid as keratolytic agent and permeation enhancer, potassium hydrogen phthalate as plasticizer,  release modifying polymers (Ethyl cellulose), and ethyl acetate as a solvent system. Initially, a solvent system was selected for optimization of formulation.

1. Evaluation of Nail lacquer:

Formulated nail lacquers were subjected to preliminary evaluation tests.

2. Physical appearance

Visual observations were made of the formulations' color, transparency, and application characteristics.(fig 5)

figure no: 5 physical appearance

3. Drying Time

Drying time for formulations F1 to F3 was found between 30 seconds to 50 seconds. It was found that as the polymer concentration increases from 0.5 % w/v to 1 % w/v the drying time increases respectively. The time required for the solvent to evaporate from the more viscous solution is more than the less viscous solution. Formulation F2 showed optimum drying time of about 40 sec. Formulation F3 showed maximum drying time as it contained higher amount of polymer.

Table no 2: Drying time of various batches

4. Smoothness to flow and gloss

Optimized formulation F2  when poured onto the glass plate was found to have ssatisfactory flow property and result in a uniform smooth film, as compared to other formulation batches.

Figure no: 6 gloss of appearance

5. Non- Volatile Content of Nail Lacquer

The increase in polymer concentration from 0.5 % to 1 % causes increase in non-volatile content of nail lacquer. Non- Volatile Content depends on polymer content. Thus, higher the polymer concentration higher is the non-volatile content of nail Lacquer.

6. Water Resistance Test

As shown in, Table 5 increase in polymer concentration increase the water resistance. Formulation F1, F1and F2 shows lower water resistance than F3.

Table no: 3 water resistant test