Formulation And Evaluation of Harbel Gel of Berberis Aristata for Anti-Psoriatic Activity

An autoimmune chronic skin condition known as psoriasis is characterized by well-defined, mildly elevated, dry, erythematous macules with silvery scales. The disease is estimated to afflict 2% of people in all age groups and both sexes, according to the modern medical system ^[1]. Psoriasis as diagnosed by modern medicine is compared to and recognised as Kiibha from Ayurvedic literature.

According to the traditional medical model, psoriasis is classified as a papulosquamous condition with scaly papules and plaques as a morphological hallmark. An autoimmune skin condition known as psoriasis causes excessive skin growth. The term "psoriasis" is derived from the Greek word "Psora" (spelt sora), which meaning "itch" whereas "Lepra" is derived from the Greek words "lopos" (the epidermis) and "lepo" (to scale) ^[2]. On the scalp, elbow, knees, lumbo-sacral region, and in the folds of the body, psoriatic lesions are distributed symmetrically ^[3]. Epidermal hyperplasia, excessive inflammatory cell infiltration into the dermis, and neovascularization are the hallmarks of the chronic, immune-mediated inflammatory dermatosis known as psoriasis. The scalp, trunk, extensor surfaces of the limbs, and the genital region are among the areas with the clinical appearance of erythematous scaly rash patches (itching and flaking skin). The prevalence rate is 2% to 3% worldwide ^[4].

Fig 1: Psoriasis

Psoriasis is influenced by a number of variables, including genetics, inflammation, metabolism, autoimmune, environment, and infection ^[5]. Skin flakiness and scale formation are symptoms of the skin disorder psoriasis. On skin that is brown, black, or white, the patches may appear pink or red and the scales may be white or silvery. On black and brown skin, the scales may seem gray and the patches may also appear purple or dark brown. Although they can grow anywhere on your body, these patches typically develop on your knees, elbows, scalp, and lower back ^[6].

Symptoms of Psoriasis: Dry, scale-covered skin patches are a common symptom of psoriasis. The patches may seem pink or red and the scales may be white or silvery on skin that is dark, black, or white. Some patients have experience itching or soreness as a result of psoriasis.

Types of Psoriasis: The different types of psoriasis are; Plaque psoriasis (psoriasis vulgaris), scalp psoriasis, nail psoriasis, guttate psoriasis, inverse (flexural) psoriasis, Erythrodermic psoriasis and pustular psoriasis (Generalized pustular psoriasis or von Zumbusch psoriasis and Palmoplantar pustulosis) ^{[9,10,11,12].}

Fig 2: Types of Psoriasis

Herbs used in psoriasis:

Herbs used in psoriasis:-

• Berberis aristata
• Mahonia aquifolium (Oregon Grape)
• Indigo naturalis
• Aloe vera
• Apple cider vinegar
• neem
• extracts of sweet whey
• capsaicin
• curcumin
• witch hazel
• licorice extract
• dandelion tea
• Trigonella arabica
• Catharanthus roseus
• Anthemis cotula

1.2 BERBERIS ARISTATA

Berberis aristata commonly known as “Daru haldi and chitra” or Tree turmeric is a spinous shrub native to the northern Himalayan region. Berberis aristata, (family-Berberidaceae) plant is intended to be used in the herbal formulations because of its potent anti psoriatic action (anti inflammatory) due to the presence of active compound berberine. In Ayurveda it’s known as Daruharidra which means plant having yellow wood and flowers ^[14]. Other synonyms of Daruharidra are Kusumbhala (flowers are utilized in making yellow dye), Katankateri, Kantakini (leaves have spinato's margin), Vishodhini (work as purifier), Krimihara (act as anthelmintic) and Pachampacha (improves liver functions).

Fig 3: Bark of Berberis aristata

B.aristata contains isoquinoline alkaloids mainly berberine which is responsible for anti-psoriatic activity. Other phytoconstituents includes oxyberberine, berbamine, aromaline, kakrachine, palmatine, oxycanthine, taxilamine, and jatrorrhizine, some of the alkaloids are reported as being found in the chloride salt form.

Fig 4: Structure of berberine

1.2.3 Botanical description

It is an erect spiny shrub, ranging between 2 and 3 meters in height wood, hard and yellow; bark, yellow to brown from outside and deep yellow from inside, removable in longitudinal strips by hand; spines (which, in fact, are modified leaves), three-branched and 1.5 cm long. The bark is covered with three-branched thorns, which are modified leaves, and can be removed by hand in longitudinal strips.

1.3 GEL

Topical gels are semi solid homogeneous preparation used to cure and treat topical diseases. Gels are more hydrophilic in nature so the rate of released drug or active ingredient was fast. A gel consists of two components; three dimensional cross linked material which contains proportionally large amounts of liquid medium to form an adequate rigid network which immobilized the liquid continuous phase. Inorganic particles and organic macromolecules both are used to form a structural network of gel. In chemical gel the particles are associated with permanent covalent bonding while physical topical gels are associated by weaker and reversible secondary intermolecular forces like hydrogen bonding, electrostatic interactions, hydrophobic interaction and Van Der Waals forces ^{[25, 26].}

1.3.2 Method for Preparation of Gel

There are 3 methods for preparation of gels.

1. Fusion method:- In this method the vehicles, gelling agents, additives and drug are blended at high temperature until a semi solid texture is formed.

2. Cold method:- In this method all the components excluding drug or active pharmaceutical ingredients are heated and blended simultaneously and then lower the temperature of formulation, then add drug and again blending was started until the gel was not formed.

3. Dispersion method:- In this method the gelling agent is stirred with water until the gelling agent swells up and then the drug is dissolved in medium and incorporated into it. Add a buffer solution to adjust the pH of the gel if necessary (the method used for the formulation of gel for the treatment of psoriasis).

3. MATERIALS AND METHODS

Table I: Role of excipients

3.2 METHODS

3.2.1 Collection of Bark of Berberis aristata and excipients: The bark of Berberis aristata is collected from the nearby nursery, Bareilly while the excipients are collected from SRMS CET (Pharmacy), Bareilly.

3.2.2 Extraction of B. aristata: The method used for extraction of mahonia B. aristata from it's bark is ethanolic extraction of Berberis aristata. It is done in following steps ^[36];

Dissolve berberis bark in ethanol (100 ml) in water bath and heat it for 1 hour

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Filter the solution after 1 hour heating

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Re-extract the bark in 50 ml ethanol for 2 consecutive times for 30 minutes respectively

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Filter the above solution separately

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Combine all 3 filtrates and concentrate it upto 50 ml by heating.

3.2.3 Preformulation studies of the Berberis extract:

Preformulation studies are needed to ensure the development of a stable as well as effective and safe dosage form. It is a stage of development during which the pharmacist characterizes the physic-chemical properties of the drug substances and its interaction with various formulation components ^[37].

Goals of Preformulation study:

? To determine the necessary physicochemical parameter of a new drug substance.

? To establish its incompatibility with excipients of formulation.

The preformulation studies of Berberis aristata extract includes;

1. Solubility: The solubility of Berberis aristata extract depends on the specific solvent used and the concentration of the extract. The solubility can be determined by dissolving the extract in different solvents like water, ethanol, methanol and non-polar solvents like chloroform and ether.

2. pH:- The pH of Berberis aristata extract can be measured using a pH meter or pH indicator paper. The extract can be diluted in water or another suitable solvent to obtain a pH measurement. Typically, Berberis aristata extract has a slightly acidic to neutral pH, ranging from around 5.5 to 7.5.

3. Drug compatibility- Drug compatibility can be determined by keeping the mixture of the drug extract and xanthan gum for 30 days in a container.

4. UV spectroscopy:- UV spectroscopy is a commonly used analytical technique in preformulation studies of compounds. It provides valuable information about the electronic structure and functional groups present in the compound. Here are some of the key things that can be determined from UV spectroscopy by taking ethanol water as reference in preformulation studies is;

a. Absorption maxima

b. Beer's law limit

Preparation of Gel for the treatment of psoriasis:

The gel for the treatment of psoriasis is prepared with the help of dispersion method is as follows;

Accurately weigh xanthan gum, taken in a beaker (labeled it as B1) and dispersed in 100 ml distilled water.

Keep aside the above B1 beaker to swell xanthan gum for half an hour and then stir it with a magnetic stirrer for another 30 minutes.

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Take 5 ml propylene glycol and the required quantity of extract in another beaker and label the beaker as B2.

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Again take 5 ml propylene glycol in another beaker labeled as B3 and add propylparaben, methyl paraben, triethanolamine and glycerine with proper stirring.

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Now, add the ingredients of B2 and B3 to B1 with continuous stirring and lastly add vitamin E oil, tea tree oil, sandalwood and perfume to it with proper mixing.

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Finally, transfer the prepared gel in a suitable container and label it.

Table II: Ingredients used for preparation of gel (100 ml)

4. EVALUATION

The evaluation parameters of the anti-psoriatic gel of B. aristata are;

1. Physical Parameters: It includes color, odor, homogeneity (degree of uniformity of the content of extract), phase separation and grittiness and these can be determined by visual inspection in presence of light.

2. pH- The pH can be calculated with the help of a digital pH meter. pH of the gels were determined by a digital pH meter by dipping the glass electrode entirely into the formulation to cover the electrode.

3. Viscosity (Brookfield viscometer)- Brookfield viscometer (Spindle type, S-62) at 10 rpm was used to determine viscosity of gel. The spindle of the brookfield viscometer was a dipped beaker containing 100g of gel. Run the instrument for 5 minutes and reading was noted in cps.

4. Stability- The stability can be determined by visual observation by observing its appearance over time (at least for 30 days).

5. Spreadability- The gel was transferred on a glass slide and covered with an equivalent slide. The slides are placed in such a way that gel is sandwiched up to 7.5 cm. A weight of 50g was placed over the upper slide which helped in forming a uniform thin layer. The weight was removed and excess adhering gel was wiped. After that 20 g weight was coupled carefully to the upper slide. Time taken to travel a distance of 7.5 cm by upper slide under influence of weight was recorded. The procedure was repeated thrice and the mean was calculated. The following formula was used to determine spreadability.

S = MxL/T

Where, S - Spreadability

M - Weight coupled to the upper slide (50 g)

L - Length of the glass slide (7.5 cm)

T- Time taken to separate the slides in seconds

6. Skin irritation- This can be tested by applying the gel on a specific area of the skin and is monitored for several hours.

7. Gelling property - It can be determined by visual inspection of thickness of gel.

RESULT AND DISCUSSION

5.1 RESULT OF PREFORMULATION STUDIES OF BERBERIS EXTRACT

Table III: Result of Preformulation Studies of Berberis aristata extract

RESULT OF EVALUATION OF ANTI-PSORIATIC GEL

Table IV: Result of Anti-psoriatic gel