FORMULATION AND EVALUATION OF OLIVE DICLOFENAC CREAM

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FORMULATION AND EVALUATION OF OLIVE DICLOFENAC

CREAM

Dr. Jigar Vyas, Patel Nidhi*, Mehvish Nagamia, Parikh Jahanvi and Patel Ayushi Sigma Institute of Pharmacy, Bakrol, Vadodara, Gujarat, Pin: 390019.

ABSTRACT

This study was performed to develop a topical cream of Diclofenac-Na which has potent anti-inflammatory activity by oral administration. At first, research was carried out on the cream base which influences the external anti-inflammatory effect of the drug. Cream of Diclofenec-Na were prepared with base of Bee-wax and Coconut butter. The cream was found to have potent effect. Therefore, in next, an optimum concentration of diclofenac –Na in cream was determined comparing the anti-inflammatory effect among the Gel preparations containing 1% of the drug. Result: Obvious effect were observed with the cream and a Gel containing 1.0% diclofenac Na and was adopted as the external topical formulation of the drug for anti-inflammatory effect.

KEYWORDS: Diclofenac-Na, Olive oil, Coconut butter, Borax, Extract of Tulsi and Neem, Beewax.

1. INTRODUCTION

Drug delivery through the skin has been a promising concept for a long time because the skin is easy to access, has a large surface area with vast exposure to the circulatory and lymphatic networks and the route is non-invasive.[1] Transdermal delivery is of great importance for drugs that may cause systemic side effects,e.g., non-steroidal anti-inflammatory drugs (NSAIDs).[2] Rheumatoid arthritisrepresents the commonest form of chronic inflammatory joint disease.[3] Arthritis is one of the most distressing and disabling syndromes encountered in medical practice.[4] Diclofenac Sodium a NonSteroidal Anti-inflammatory agent is frequentlyprescribed for the long term treatment of RheumatoidArthritis, Osteoarthritis and Ankylosing Spondylitis.[5] Delivery of Diclofenac Sodium via skinoffers the potential advantage of by passinggastrointestinal first pass metabolism associated withoral

Volume 10, Issue 5, 1424-1437 Research Article ISSN 2278 – 4357

*Corresponding Author Patel Nidhi

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administration.[6] There is great interest to develop non-oral dosage forms of diclofenac sodium to minimize its gastric side effects and to provide relatively consistent drug levels at the application site for prolonged periods.[2] However, effective permeationof the drug through skin is difficult to achieve dueto its intrinsically poor permeability, though this isrelatively good compared to other commonlyused NSAIDs.[6] Skin permeation enhancerscan improve drug skin penetration.[7] The present research has been undertaken with the aim to develop a topical Diclofenac Sodium cream formulation.

1.1 INGREDIENTS USED FOR CREAM 1.1.1. Diclofenac sodium

This medication is used to relieve joint pain from arthritis.

Diclofenac belongs to a class of drugs known as nonsteroidal anti-inflammatory drugs (NSAIDs).

Diclofenec falls under the NSAIDS class of drug.

Some beneifts in of NSAIDS in the pharma world are as follows:[8] 1.) They are a class of medicines available by prescription and OTC.

2.) They are some of the most commonly used medicines for pain and fever.

3.) used to treat medical conditions such as arthritis, menstrual cramps, headaches, colds, and the flu.

4.) work by blocking the production of certain chemicals in the body that cause inflammation.[8]

1.1.2. Bees wax

Beeswax is an excellent addition to cosmetic products, for many reasons.

When used in lotions and creams, beeswax creates a barrier which helps to seal moisture into the skin.

This barrier also helps to protect the skin from environmental toxins and irritants.

Beeswax helps to thicken homemade cosmetics and lotions because it is solid at room temperature and has a relatively high melting point of 147 degrees Fahrenheit. This is especially helpful in recipes that include high amounts of coconut oil, which has a low melting point, or other oils that are liquid at room temperature.

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1.1.3. Coconut Butter Increases hydration

Coconut oil helps bolster your skin protective barrier layer, trapping moisture inside and keeping skin supple and hydrated.

Reduces inflammation

Coconut oil has anti-inflammatory properties, making it beneficial for irritated, chafed skin. Increases collagen production

Thelauric acid content in coconut oil has a beneficial effect on collagen production. Collagen helps skin maintain firmness and elasticity. Helping skin maintain and produce collagen might eliminate the formation of some fine lines and wrinkles.

Lightens dark patches. According to beauty bloggers like DIY Remedies, coconut oil can lighten skin and may help reduce the appearance of dark spots or uneven skin tone. Adding lemon juice may enhance this effect.[11]

1.1.4. Olive oil

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and oleocanthal which may prevent aging and repair skin damage. Olive oil is non-toxic, anti-microbial, and hypoallergenic.[12]

Here are some ways to use olive oil on your skin. 1.) Hand moisturizer

2.) Moisturizer for babies 3.) Eye-makeup remover

1.1.5. Borax

When borax is dissolved in water it produces boric acid and sodium hydroxide. The sodium hydroxide interacts with cerotic acid in the beeswax a free fatty acid that makes up about 13% of beeswax by weight and forms an anionic emulsifier, while the boric acid buffers the system. The emulsifier created by the chemical reaction made the oil and water parts of the cold cream less likely to separate on standing, so cold creams made with borax were more stable.[13,14]

1.1.6. Tulsi extract

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1.1.7. Neem extract

Neem oil comes from the seed of the tropical neem tree, also known as Indian lilac. Neem oil has a wide history of use as a folk remedy around the world, and has been used to treat many conditions. Although it has a harsh odour, high in fatty acids and other nutrients, and it is used in a variety of beauty products like skin creams, body lotions, hair products, and cosmetics.[20]

Neem oil contains many ingredients that are extremely beneficial to the skin. Some of those ingredients include:

Fatty acids (EFA) Limonoids

Vitamin E Triglycerides Antioxidants Calcium

It has been used in beauty regimens and skin care to: Treat dry skin and wrinkles

Stimulate collagen production Reduce scars

Heal wounds Treat acne

Minimize warts and moles

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1.2 Some of the marketed Diclofenac Formulation

Fig. 1.1: Diclofenac gel. 2.0 MATERIAL AND METHODS

2.1 FOR DICLOFENAC SODIUM CREAM BASED FORMULATION

2.1.1 Material: Diclonefac sodium, Beewax, Cocnut butter, olive oil, Borax, Tulsi extract and Neem extract.

Table 2.1: Formulation of Diclofenac cream.

2.1.2 METHOD

1. Grate the white Beewax and Cocnut butter and olive oil and melt in China dish, by heating on the water bath up to 70Defree C.

2. In a glass beaker, dissolve borax in water and heat up tp 70 Degree C.

Ingriendients Category Proportion

Diclonefac Na Nonsteroidal anti-inflammatory Drug 1% Beewax Thickening agent and Emulsifier 11% Coconut butter Thickening agent 11% Olive oil Solvent and Natural Emollient 64.8%

Borax Emulsifier 2.2%

Tulsi extract Anti-Bacterial 5%

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3. When both Oily and aqueous phases reaches the same temperature, gradually add Borax solution to the melt of Beewax drop by drop, with constant stirring.

4. Stir continuously until it becomes cool. When the temperature loweres to 40-50 Degree C, until a homogenous semi solid mass is obtained.

Fig. 2.1: Prepared Olive Diclofenac sodium cream. 2.2 FOR DICLOFENAC SODIUM GEL BASED FORMULATION

2.2.1. Material: Diclofenac sodium, carbopol, Neem extract, Tulsi extract, Methylparaben, Glycerin, Polyethylene glycol

Table 2.2: Formulation of diclofenac gel.

Formulation Ingredient Category Proportion

Diclofenac sodium Non-steroidal anti-inflammatory drug 1%

Carbopol Gelling Agent 1%

Neem Extract Anti-bacterial 47.75%

Tulsi Extract Anti-microbial 40%

Methyl Paraben Preservative 0.25%

Glycerin Gel 5%

Polyethylene glycol Smoothing agent 5% 2.2.2 METHOD

Prepration of neem Extract

10% fresh Neem Leaves are grind & boiled in 100ml Distilled water.Filter mixture. Prepration of tulsi Extract

10% fresh tulsi Leaves are grind & boiled in 100ml of Distilled wayer.Filter mixture. Formulation of diclofenac gel

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mixing of extract in gel base. Collapsible tube were used for filling of prepared gel. these formulation were stored in cool and dry place.

3.0 ORGANOLEPTIC EVALUATION

Physical parameters such as color and appearance were recorded.

3.1 Viscosity: Viscosity of gel was measured using Brookfield viscometer (Brookfield viscometer RVT) with spindle number.[21]

3.2 Extrudability: The gel formulations were filled in standard capped collapsible aluminum tubes and sealed by crimping to the end. The weights of the tubes were recorded. The tubes were placed between two glass slides and were clamped. 500g was placed over the slides, and then, the cap was removed. The amount of the extruded gel was collected and weighed. The percent of the extruded gel was calculated (>90% extrudability: Excellent, >80% extrudability: Good, and >70% extrudability: Fair).[22]

3.3 Spreadability: Spreadability was determined by the apparatus which consists of a wooden block, which was provided by a pulley at one end. By this method, spreadability was measured on the basis of slip and drag characteristics of gels. An excess of gel (about 2 g) under study was placed on the ground slide. The gel was then sandwiched between this slide and another glass slide having the dimension of fixed ground slide and provided with a hook. A 1 kg weight was placed at the top of the two slides for 5 min to expel air and to provide a uniform film of the gel between the slides. Excess of the gel was scrapped off from the edges. The top plate was then subjected to pull of 80 g with the help of string attached to the hook, and the time (in seconds) required by the top slide to cover a distance of 7.5 cm was noted. A shorter interval indicated better spreadability.[23] Spreadability was calculated using the following formula

S=M×L/T Where,

S = Spreadability

M = Weight in the pan (tied to the upper slide) L = Length moved by the glass slide T = Time (in sec.) taken to separate the upper slide from the ground slide

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to detect any change with time. 1 g of gel was dissolved in 100 ml distilled water and kept aside for 2 h. The measurement of pH of formulation was done triplicate, and average values are calculated.[24-26]

3.5 Homogeneity: All developed gels were packed in containers and then tested for homogeneity by visual inspection. They were tested for their appearance and presence of any aggregates.

3.6 Grittiness: All the formulations were evaluated microscopically for the presence of any appreciable particulate matter which was seen under light microscope. Hence, obviously the gel preparation fulfills the requirement of freedom from particular matter and form grittiness as desired for any topical preparation.[24-26]

3.7 Stability study: ICH guidelines were followed for stability study. The formulated gel was filled in collapsible tubes and stored at different temperatures and humidity conditions, namely 25±2°C/60±5% RH, 30±2°C/65±5% RH, and 40±2°C/75±5% RH for a period of 3 months and studied for appearance, pH, and spreadability.[27,28]

Table 3.1 Evaluation parameters study results for Cream.

Treatment Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7

Rats A A A A A A A

3.8 Skin irritation test: The intact skin of Wistar rats of either sex with average weight 150– 200 g was used. The hairs were removed from the rat 3 days before the experiment. Prepared gel formulations were used on the test animal and gel base on control group. The animals were treated daily for 7 days, and erythema and edema on the treated skin were examined.[29] Table 3.1.1 Skin irritation study results over 7 days period for Cream.

Parameters evaluated Study period

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PH Measure 6.79 6.81 6.78 6.80

A-No reaction, B-slight patchy, C- Slight but confluent or moderate but patchy erythematic, D- Moderate erythematic, E- Severe erythematic with or without edema.

Fig.3.1 Application of Diclofenac cream on Hand. Table 3.2 Evaluation parameters study results for Gel.

Parameter Studies result

PH 7.4

Spreadability(g cm/s) 5.6 Viscosity(dynes/cm) 0.94 x 10-3 Homogenecity Very good Table 3.2.1: Stability study for Gel based formulation.

Formulation Month Appearance Ph Drug content (%) 0 clear 7.4 99.81 1 clear 7.4 98.27 2 clear 7.3 97.54 3 clear 7.3 96.91 Table 3.2.2: Percentage remaining of drug content at zero time.

Absorption of Standard

Absorption of Sample

Percentage of active

drug in the sample Mean

Standard Deviation

0.625 0.623 99.28% 0.624 0.001414

Table 3.2.3: Percentage remaining of drug content after 1 month. Absortion of

Sample

Percentage of active

drug in the sample Mean

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Table 3.2.4: Percentage remaining of drug content after 2 month. Absortion of

Sample

Percentage of active

drug in the sample Mean

Standard deviation At 25 + 1◦C 0.604 96.25% 0.6145 0.014849 At 40 + 1◦C 0.597 95.13% 0.611 0.019798 At 65 + 1◦C 0.595 94.81% 0.61 0.021213

Fig. 3.3: Absorption spectra of Diclofenac sodium. 4.0 RESULT AND DISCUSSION

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5.0. CONCLUSION

The present cream formulation was developed by taking into consideration that in cream formulations there is present no direct contact of active drug with stomach wall. This can be a reason to remove the chances of epidermis mucosal damage to a reasonable level that is caused by the use of solid dosage forms of NSAIDs. The Diclofenac sodium cream is found to be effective to mimic the pain and inflammation.

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