INTRODUCTION:

A transdermal patch is a treated tenacious patch that's placed on the skin to deliver a specific cure of drug through the skin and into the bloodstream.^1,2

An advantage of a transdermal medicine delivery route over other types of drug delivery (similar as oral, topical, intravenous, or intramuscular) is that the patch provides a controlled release of the drug into the case, generally through either a pervious membrane covering a force of drug or through body heat melting thin layers of drug bedded in the glue.^3,4,5

Transdermal route of medicine delivery can achieve original and systemic remedial goods. Transdermal medicine delivery is a seductive cover for oral medicine administration as it bypasses first pass metabolism, gastrointestinal goods and, also, it can overcome the poor case compliance associated with other medicine delivery routes. Transdermal medicine delivery is tone- administered, allowing the medicine to pass through complete skin over a controlled period of time to achieve an original or systemic effect. medicines can be delivered through transdermal patches in dissolved lipid- grounded form enabling them to produce the needed efficacity.^6,7

Transdermal drug delivery systems can be modified using a number of permeation enhancer materials so that the drug absorption profile can be controlled in a predictable manner. Various transdermal drug delivery systems have different mechanisms to control the drug release rate, such as single layer or multilayer drugs in the adhesive system, vapour patch, membrane moderated, micro reservoir transdermal systems, matrix systems containing drug-in-adhesive or matrix-dispersion systems.^8.9,10

NATURAL INGREDIENTS:

CAMPHOR:

Camphor (Karpura) is a white crystalline substance with a strong odour and pungent taste derived from the woods of camphor laurel and other trees related to the laurel family. Camphor tree is native in India, China, Mongolia, Japan and Taiwan. Camphor is obtained through steam distillation, purification and sublimation of wood, twigs and bark of the tree. There are many pharmaceutical applications for camphor such as topical analgesic, antiseptic, antispasmodic, antipruritic, anti-inflammatory, anti-infective, rubefacient, contraceptive, mild expectorant, nasal decongestant, cough suppressant, etc.¹⁰

Camphor is easily absorbed through the skin and can also be administrated by injection, inhalation and ingestion. Karpura plays various important properties useful in cure of certain diseases. It acts as antispasmodic, anti-inflammatory, analgesic, antiseptic, anti-infective, rubefacient, contraceptive, cough suppressant, mild expectorant and nasal decongestant. It can also be used for injection, ingestion or inhalation purpose.

Camphor has several chemical varieties, each with different essential oil compositions. The leaf of Cinnamomum camphora contains camphor, as the main component along with cineol, linalool, eugenol, limonene, safrole, a-pinene, ß-pinene, ß-myrcene, a-humulene, p-cymene, nerolidol, borneol, camphene and some other components.

Dhanvantari Nighantu Sodhala mentioned Pakva (artificial), Chinaka and Apakva (natural) varieties of Kurpura. In the making of patch of our transdermal patch different types of camphor are used.

Chunekarji explained four varieties of camphor viz.

1. Bhimseni or Baras Karpura (D. Camphora)

2. Cini or Japani Karpura (D. camphora)

3. Patri or Nagi Karpura- Blumea balsamifera; B. lacera, B. desiflora etc.

4. Krutima Karpura - Synthetic variety camphor.

MUSTARD OIL:

Mustard is a condiment made from the seed of mustard plant white or yellow mustard, Sinapis alba; Brown mustard, Brassica juncea; or black mustard, Brassica nigra. It is used as an ingredient in many dressings, glazes, sauces, soups, and marinades. It is one of the most popular and widely used spices and condiment in the world.

Mustard oil helps in treating antiinflammation, joint pain, back pain and helps in improving rage of motion flexibility, circulation, decrease stress and release tension. While experiencing pregnancy back pain gently exercise such as stretching and light movements will decrease spasms of the muscles and help decrease back pain.

Benefit of Mustard Oil

Mustard oil contains a compound that could be useful for reducing inflammation: allyl isothiocyanate.

Uses of Mustard Oil

· Treat arthritis

· Soothe aches and pains

· Decrease inflammation from chest conditions such as bronchitis and pneumonia

· Relieves Body pain

CLOVE OIL:

Clove oil contains compound called eugenol Syzygium aromaticum that helps in treating acne byreducing the inflammation and redness. The antibacterial and antiseptic properties of cloves kill acne- causing bacteria and keep breakouts at bay.

Clove are the aromatic flower buds of a tree in the family Myrtaceae.

They are native to the Maluku Islands in Indonesia and are commonly used as spice, flavouring or fragrance in consumer products, such as toothpaste, soaps or cosmetics.

Cloves may be used to give aromatic and flavor qualities to hot beverages, often combined with other ingredients such as lemon and sugar.

OBJECTIVES:

In ancient times the people in India used to dissolve the camphor in mustard oil and clove oil and massage thoroughly in their whole body. The combination of camphor, mustard oil and clove oil provides relief to the joint pain, or pain in any other part of the body. The solution of the compounds led to greasiness, inconvience, and cannot travel, the oil sticks in the hand and it is uncomfortable to work with it. Due to the inconvenience in the daily life routine. We came with the solution of transdermal patches to reduce the inconvenience and it can help to work without any disturbance in your daily life routine.

· Combats Pain and Inflammation

· Reduces the Time It Takes to Heal from Injuries

· Increases flexibility and mobility

· Lowers aches and sprains

ADVANTAGES OF PATCHES:^11,12

· Knee Relief Patches is a topical herbal patch.

· It assists you in masking your pain.

· It provides pain and inflammation relief.

· This herbal pain reliever is effective for all muscle pain and stiffness types.

· The Patch is ready to use in three minutes.

· Knee Relief Patches provide 12 hours of continuous relief.

· It is a completely natural, safer, and side-effect-free alternative.

· The Patch can be applied at any time and in any location.

· It continuously administers medication to the painful area.

· Knee Relief Patches are water-resistant patches that can be used at any time.

· Knee Relief Patches are completely natural and have no side effects.

· This Patch is unlike any other pain reliever.

MATERIALS AND METHODS:

Materials:

Camphors were purchased from local market, Gondia. Mustard oil was extracted at M.I.B.P. Lab, Gondia. Clove oil was extracted in M.I.B.P. Lab, Gondia. HPMC, EC, PEG-400, PVA, Tween 20 were of analytical grade were purchased from Burgyoneburbidges & co. India.

Preparation of patch

The active pharmaceutical ingredient was prepared by combining requisite amount of camphor in mustard oil and 2-3 drops of clove oil is added and dissolved in ethanol. The drug matrix was prepared by dissolving HPMC and EC in methanol. To this solution PEG 400 was added and stirred. The uniform dispersion obtained was casted on PVA backing membrane and dried at room temperature for 24hrs.The dry films were removed and wrapped in aluminium foil and kept in a desiccator until used. The so prepared films were stick to adhesive layer of bandage which was purchased from local market.^12,13

Table No. 01: Formulation of Transdermal patches

Sr No	Ingredients	F1	F2	F3	F4	F5
1.	Herbal API mixture	10ml	10ml	10ml	10ml	10ml
2.	HPMC	2.5gm	3.0gm	3.5gm	2.6gm	3.6gm
3.	EC	1gm	1gm	-	1gm	-
4.	PVA	1gm	-	1gm	-	1gm
5.	Tween 80	1ml	1ml	1ml	1ml	1ml
6.	Glycerine	2ml	3ml	1.5ml	1ml	2ml
7.	Ethanol	25ml	25ml	25ml	25ml	25ml
8.	Chloroform	25ml	25ml	25ml	25ml	25ml
9.	Distilled water	q. s	q. s	q. s	q. s	q. s

Figure no 1: Prepared Transdermal Patch in Lab

EVALUATION OF HERBAL JOINT PAIN RELIEF PATCH:

Physicochemical appearance:

In the R&D the formulated patches were evaluate the colour, texture, uniform, flexible in their physical appearance and free from entrapment of air bubble.^16,17,18

Thickness of the patch:

The thickness of the drug loaded patch is calculated in different points by using a digital micrometer, or travelling microscope, dial gauge, screw gauge, and determines the average thickness and standard deviation for the same to ensure the thickness of the prepared patch. Patch will have an equal thickness at every point. The variation of thickness within the patch and patch to patch can be calculated.^16,17,18

Moisture content: Individually weighed patches are kept in the desiccators having fused calcium-chloride at room temperature for 24hours. After 24Hours the patches are to be reweighed and percentage moisture

content is calculated by the formula

% Moisture content

= (Initial weight –Final weight) X 100/initial weight

Moisture uptake: The weighed films are to be kept in desiccators at room temperature for 24hrs. containing saturated solution of potassium chloride in instruct to maintain 84% RH. After 24hrs. the films are to be reweighed and determined the percentage moisture uptake from the mentioned %Moisture uptake = (Final weight – Initial weight X 100)/Initial weight.^16,17,18

Folding endurance: This was determined by repeatedly folding the film at the same place until it broke. The number of period the films could be folded at the same place without breaking/cracking gave the value of folding endurance.^16,17,18

Weight uniformity: A specified area of the atches was cut carefully in different parts and afterward weighed in a digital balance. The average weight and standard deviation values were calculated from the individual weight.^16,17,18

Evaluation of Drug content determination: Amount of drug entrapped in a patch was determined by completely dissolving patch of size 2×2 cm2 in 100ml phosphate buffer solution (PH 7.4). complete dissolution was achieved by placing the solution containing patch on shaker for about 24hours. Solution was then filtered and drug content was estimated spectrophotometrically at 210nm after suitable dilution.^16,17,18

Studies In-vitro permeation:

Permeation studies are carried out in order to determine transition of drug from patch to skin microcirculation. In this study synthetic membrane like cellulose nitrate was placed between the donor and receptor compartment of Franz diffusion cell. Receptor compartment was filled with phosphate buffer of ph. 7.4. Transdermal patch was placed upon the cellulose nitrate membrane was towards the receptor compartment having phosphate buffer. The receiver compartment was maintained at room temperature and was continuously stirred with the help of magnetic stirrer. Samples were withdrawn at specific time interval and equal amount of phosphate buffer was replaced each time to maintain volume of receptor compartment at a constant level. Samples withdrawn were then analyzed for their absorbance and concentration was then calculated.^16,17,18

pH of the patch:

The pH meter was calibrated using standard buffer solution. About 1 patch dissolve in buffer solution and dissolved in 50ml of phosphate buffer and its pH was measured. In pH meter with help of apparatus baker, pH meter, stirrer, wash bottle.^16,17,18

RESULTS AND DISCUSSION:

Physico-Chemical evaluation:

All the patche were thick, yellowish transparency, smooth and clear.

The thickness ranges were 0.155±0.007mm. The results showed that the patches were uniform, as it was evidenced by SD value, which were less than 0.01 all the patches. (Table-2).

The moisture uptake was found to be higher in batches F1, F2, F3, F4 and F5, which might be due to HPMC. The lower moisture content in the formulations helps them to remain stable and become a completely dried and brittle film. Again, low moisture uptake protects the material from microbial contamination and bulkiness. The moisture uptake of batch F1, was measured and found to be 4.32%.

Table no. 2. Physicochemical evaluation of transdermal patch

Evaluation parameters	F1	F2	F3	F4	F5
Colour	Pale yellow	Pale yellow	yellowish	Pale yellow	Pale yellow
Clarity	Translucent	Translucent	Translucent	Translucent	Translucent
Texture	Smooth	Smooth	Smooth	Smooth	Smooth
Thickness of patch	0.15±0.007mm	0.13±0.047mm	0.15±0.027mm	0.16±0.012mm	0.15±0.034mm
Moisture uptake	0.162	0.166	0.163	0.164	0.162
Folding endurance	95±10	82±12	96±31	79±53	94±34
Weight uniformity	0.159±11	0.169±13	0.156±32	0.165±65	0.166±54
Drug content	84.79±32	78.98±65	78.941±11	78.63±54	84.63±13
pH of Patch	6.4	6.2	6.2	6.3	6.2

The folding endurance values of all the patches were found satisfactory which indicates that the patches prepared using PEG 400 in a concentration of 30% w/w of polymer were having optimum flexibility and were not brittle.

The pH test was performed for base formulation for 30 days. The pH of the patch was found to be in range of 5.6 to 6.8 which is good for skin pH all of the formulation of patch were shown pH nearer to skin required, but pH of formulation. F1, F2, F3, F5 shows variation in pH restored for long period of time formulations F4 shows stable pH.

The drug content ranged 84.79%. All formulations were acceptable with Camphor, Mustard oil and Clove oil. From the above observation, it was concluded that all the patches were show ideal physical characteristics.

IN-VITRO PERMEATION STUDIES:

The in vitro skin permeation of drug (Thymol camphor, Menthol Camphor, Bhimseni Camphor, Mustard Oil, Clove Oil) from various transdermal patches using locally fabricated Franz type of diffusion cell. The diffusion cell consists of two parts; the upper part that is donor compartment and contain active ingredient and the carrier patch; the bottom part contains the receptor solution, the water jacket for temperature control, and the sampling port. The effective permeation area of the diffusion cell and receptor and cell volume was 1cm2 and 20ml, respectively. The temperature was maintained at 37± 2`C. the receptor compartment contained 20ml of phosphate buffer IP PH 7.2 stirred by magnetic stirrer. The permeability studies were carried out across pig ear skin. Sample 5ml were withdraw and replace with the same volume of fresh receptor solution, to the sampling port of the diffusion cell predetermine time intervals till 6hrs.the absorbance of withdrawn samples were measured at 280nm for drug (Thymol camphor, Menthol Camphor, Bhimseni Camphor, Mustard Oil, Clove Oil). Find out the %Cumulative Drug release of each formulation. Plot the graph between % Cumulative Drug release v/s time, which is present in figure no. 22 (A, B, C). The experiments were done in triplicates, simultaneously blanks were also run and the average value reported.

Fig no. 3 Laboratory franz diffusion cell.

Table No.3. In-vitro released data for transdermal patch

Time (minutes)	F1	F2	F3	F4	F5
0	0	0	0	0	0
10	5.88	7.65	8.35	6.75	7.45
20	10.12	10.22	12.36	11.23	10.35
30	25.55	24.35	25.2	24.5	25.25
40	33.65	33.88	32.55	30.04	33.06
50	50.55	42.99	40.95	45.55	49.65
60	60.33	54.68	55.65	52.55	59.98
120	65.55	63.75	58.05	54.97	69.45

Fig no. 4. In-vitro released data for transdermal patch

CONCLUSIONS:

Transdermal drug delivery system has been in existence for a long time. In the past, the most commonly applied systems were topically applied creams and ointments for dermatological disorders. Mustard oil, Camphor and Clove Oil were used for its analgesic property. In the present investigation, herbal transdermal patches were formulated using HPMC and EC polymer by solvent evaporation technique. The developed formulation showed good physicochemical properties like thickness, weight variation, drug content, folding endurance, moisture content. As per the result of diffusion study we can conclude that the formulation exhibited significant analgesic activity and the promising analgesic effect may be attributed which seems to be responsible. The result indicates that maximum release shows satisfactory results. So, it can be concluded that such a medicated adhesive type patches of herbal ingredient could be a good carrier in transdermal drug delivery as well as topical route for joint pain relief.

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Received on 15.12.2023 Modified on 13.03.2024

Research J. Topical and Cosmetic Sci. 2024; 15(1):27-32.

DOI: 10.52711/2321-5844.2024.00005