Formulation and Evaluation of Transdermal Patches of Meloxicam by Solvent Casting Method

Compared to the preceding two decades, changes in the area of medical delivery are taking place much faster now. Better patient compliance and an important aspect of new methods of drug delivery is effectiveness(1,2). Exploring more recent body interfaces for drug delivery has been an extreme approach. One of these is transdermal drug delivery, which utilizes human skin as a portal for the systemic administration of medication molecules. Among the devices that fall into the category of controlled drug delivery is the transdermal drug delivery system, or TDDS, whose purpose is to administer the medication through the skin at a precise and regulated pace.(1) TDDS is a painless technique that applies a drug formulation to healthy, unbroken skin to distribute medication systemically(3,4). Without accumulating in the dermal layer, the medication first penetrates the stratum corneum before moving on to the deeper epidermis and dermis. Drugs can be absorbed systemically through the dermal microcirculation once they reach the dermal layer(5,6). Compared to other traditional drug delivery methods, TDDS has numerous benefits(7–10). Meloxicam (mlx) belongs to the family of oxicam chemicals. Rheumatoid arthritis (RA), osteoarthritis (OA), and juvenile RA are all treated with it because to its analgesic, antipyretic, and anti-inflammatory qualities. On the market, it is available in parenteral and oral dosage forms. Although mlx is generally well tolerated, it does cause some side effects, the most prevalent of which are gastrointestinal. The oral dosage ranges from 7.5 to 15 mg. The goal of this research is to develop a dissolvable patches for meloxicam (MLX) that has higher penetration bypassing the systemic circulation and analyze the various materials needed to optimize the formula. The mixture was poured in a petri dish. The patch was chopped into smaller patches that resulted from a mold after it had dried completely. The objective of this study is to create meloxicam (MLX) dissolvable patches with greater penetration that avoid the systemic circulation and to examine the different components required to optimize the formula. A petri dish was used to cast the mixture. After the patch had completely dried, it was cut into smaller patches that were the result of a mold (11).

Epidemiology of rheumatoid arthritis

Osteoarthritis

According to the Arthritis Foundation, 32.5 million people in the US and 500 million people globally (about 7% of the world's population) suffer with osteoarthritis (OA). According to the Arthritis Foundation, osteoarthritis affects 15% of adults over 60 worldwide. The sixth most prevalent disability worldwide is osteoarthritis. A review published in The Lancet Discovery Science in November 2020 found that four-fifths of the global OA burden is caused by knee osteoarthritis. According to the Osteoarthritis Action Alliance, physicians in the United States conduct one million knee and hip replacement procedures annually due to OA.

Rheumatoid arthritis

According to the Institute for Health Metrics and Evaluation's 2019 Global Burden of Disease research, Rheumatoid arthritis (RA) affects over 18 million people globally. According to the American College of Rheumatology, about 1.3 million Americans suffer from RA. Of those with RA, around 75% are allocated female at birth (AFAB). According to the Arthritis Foundation, 6.4 million ambulatory (non-hospital) visits globally resulted in a diagnosis of RA in 2011.In 1990, 2.1 million adults in the US suffered from RA. According to the National Arthritis Workgroup, this figure has probably decreased as a result of fewer cases and more stringent classification standards.

Fig 1. Epidemiology of Arthritis

The API and excipients (table 1) were collected from the laboratory of Dr. D. Y. Patil college of pharmacy, Akurdi.

Table 1: List Of Materials Used

Preparation of transdermal films:

Meloxicam transdermal patches were prepared by solvent casting technique in petri plate.

The backing membrane was prepare by pouring a 2 % (w/v) polyvinyl alcohol (PVA) solution followed by drying at 60 °c for 6 h.

The drug reservoir was prepared by dissolving HPC in ethanol (8ml)

Add 5-6 drops of propylene glycol used as plasticizer

Drug is dissolve in another container was added to the reservoir under slow stirring with magnetic stirrer

The mixture was spread over PVA film and dried at room temperature

Fig 2. Transdermal Patches (F1, F2. F3)

The prepared meloxicam transdermal patches were evaluated as mentioned below:

Physical appearance:

Every prepared patch was examined visually for color, clarity, smoothness, and flexibility.

Thickness of the patch:

The thickness of the patches was measured with a screw gauge at several locations.

Weight of the patch:

An electronic balance was used to determine the weight of each of the three patches that were removed from each batch. After that, the average weight of a single patch was calculated.

Folding endurance:

A tiny strip of patches measuring about 2 by 2 cm was folded repeatedly at the same spot until it broke in order to measure folding endurance. The value of folding endurance was determined by counting the number of times patches could be folded in the same spot without breaking(11).

Percentage flatness:

In order to measure the variation in length due to non-uniformity in flatness, longitudinal strips were cut from each film, one from the center and two from either side. The length of each strip was measured without the application of additional pressure, and the percentage constitution equivalent to 100% was calculated.

Percentage variation for strip=[measured length of strip?/ length of center strip] ×100

Percentage moisture content:

Studies on moisture content showed that although a rise in the concentration of hydrophobic polymers caused the moisture content of the films to decrease, an increase in the concentration of hydrophilic polymers was exactly proportionate to the increase in the moisture content of the films. The produced formulations had a low moisture content, which may have contributed to their stability and decreased brittleness over time.

After being individually weighed, the produced films were stored for 24 hours at room temperature in a desiccator filled with fused calcium chloride. After weighing the film once more, the following formula was used to determine its % moisture content:

Percentage moisture uptake = [final weight-initial weight / initial weight] x100

Moisture uptake:

The prepared patches were placed in desiccators with silica gel at room temperature for 24 hours. After that, they were weighed and moved to other desiccators where they were exposed to 75% RH using a saturated sodium chloride solution at 25°C. The provided formula was used to calculate the moisture uptake capacity.(11)

In vitro drug release studies:

The manufactured film was positioned on the cellulose membrane and connected to the diffusion cell. The diffusion cell is filled with the phosphate buffer solution. After 24hr the drug content of the sample was determined using a UV Spectrophotometer at 429nm.

Preparation Of Phosphate Buffer:

For preparation of buffer solution whey the ingredient as shown in [Table 3] in volumetric flask.(12)

Table 3: Composition of Phosphate buffer pH 7.4

RESULT AND DISCUSSION:

Description:

Meloxicam was physically examined for color and odor. It is yellow crystalline powder with mild, characteristic odor.

Solubility:

Meloxicam has very poor solubility in water. At room temperature about 25°c, the solubility is about 0.15–0.3 mg/ml.

In organic solvents like ethanol, methanol, and acetone, meloxicam has very good solubility; solubility varies according to the specific solvent used and temperature.

Melting point:

The melting point of meloxicam was found to be 258°c (496.4°f). This high melting point is consistent with its crystalline structure, which makes it stable under normal conditions but also contributes to its poor solubility in water. As melting point of drug was found nearby to standard value thus it is clear that the drug is pure.

Drug Interaction Studies:

UV-Visible interaction experiments were conducted to confirm the drug's interaction with the polymer. Both the drug with polymer and the drug alone were observed in the UV-Visible overlay spectrum. It demonstrates that no drug-polymer interactions were discovered.

Evaluation Studies:

Physical appearance:

Thickness:

The thickness of the prepared patches varies between 0.257 mm ± 0.017 to 0.233 mm ± 0.013. Patch consistency is shown by low standard deviation values. [Table 4]

Weight Variation:

The weight of the prepared transdermal patches for different formulations ranged between 1.91mg ± 0.008 to 1.933mg ± 0.013 mg. The produced patches' weight uniformity variation fell within an acceptable limit. [Table 4]

Folding endurance:

Folding endurance values varied between 49 ± 3.44 and 48 ± 3.63. The outcome was deemed satisfactory, suggesting that the patches will remain intact and not shatter when put to use. [Table 4]

Percentage flatness:

The flatness for F1 is: Mean=98.15%andStandard Deviation=±1.31%

The flatness for F2 is: Mean=100%andStandard Deviation=±0%

The flatness for F3 is: Mean=100.67%andStandard Deviation=±0.47%

Shown in [Table 4]

The results are depicted in Table 4: Moisture content and Moisture uptake of meloxicam transdermal patch

Compared to other preparations, patches made with HPC have higher percentages of moisture content and moisture uptake. This is due to HPC's great affinity for water and its hydrophilic character. As a result, patches made solely with HPC absorb more moisture, increasing their moisture content and uptake. On the other hand, patches made with less hydrophilic polymers or without HPC have reduced moisture content and moisture absorption. This is mostly because, in comparison to more hydrophobic or less water-attracting materials, HPC is more water-attracting and water-retaining.