Development And Characterization of Bilayered Tablet of Paracetamol & Diclofenac Sodium

The most popular method of administering drugs is orally. This is still the recommended approach. Patient acceptability, ease of administration, precise dosage, economical production techniques, and often longer product shelf life are the reasons for the route's popularity. Due to the versatility in designing dose forms, sustained release systems have also been provided via this approach [1]. A tablet with subunits that are either the same (homogenous) or different (heterogeneous) is referred to as a bilayer tablet. This concept was established in order to provide sustained release of the medicine. When two distinct incompatible ingredients or the release profiles of the medications differ, bilayer tablets are chosen..[2-3] Conventional dose forms typically result in changes in the concentration of the medication in the blood and tissues, which leads to unfavorable toxicity and ineffectiveness. We developed the idea of a regulated medication delivery system in response to the issues of recurrent dosage and irregular drug absorption.

By localizing the drag at the site of action, these delivery methods aim to maximize medication efficacy by reducing the frequency of dosing. This lowers the dosage needed and ensures consistent drug administration. Sustained medication administration makes sense since it increases drug efficacy and safety, which in turn increases patient compliance.[4-5] Non-steroidal anti-inflammatory drugs are crucial for treating rheumatic arthritis and reducing pain and inflammation. A higher dosage is required for NSAIDs to effectively treat arthritis. Disorientation, ulcerative stomatitis, stomach irritation, and abdominal discomfort are among the negative effects that come with higher dosages [6]. Nevertheless, plasma concentrations can be maintained within the therapeutic range for a long time using a sustained and immediate release bilayered drug delivery system that includes an appropriate NSAID and an upper gastrointestinal tract-absorbed H receptor antagonist Additionally, it improves bioavailability, which reduces dosage frequency and boosts patient adherence.

MATERIAL

Diclofenac sodium and paracetamol were taken from a gift sample provided by Brothers Pharmaceutical Rajasthan. and magnesium stearate, sodium metabisulphite, lactose, talc, gelatin, propylparaben, and starch (maize) were acquired from Central Drag Laboratory Delhi (CDH). Every other chemical used was of analytical quality.

METHODS: DIRECT COMPRESSION

The direct compression method for bilayer tablets of paracetamol and diclofenac sodium involves a step-by-step procedure to create a tablet with two distinct layers, each containing a different active ingredients The process begins with the preparation of two separate powder blends.

Fig 1. Compression of Tablet

1. Preparation of Powder Blends: Paracetamol and diclofenac sodium were each blended  with excipients like binders, fillers, disintegrants, and lubricants. Usually, the diclofenac sodium layer was made for sustained release, whereas the paracetamol layer was made for instant release.
2. Blending: The individual powders for each layer were carefully mixed to ensure uniformity in the distribution of active ingredients and excipients.
3. Compression of First Layer: The first powder blend (paracetamol) was compressed into the lower half of the tablet die using a tablet press. The layer was compressed to a specific hardness and thickness to ensure proper release of the drug.
4. Compression of Second Layer: After the first layer was formed, the diclofenac sodium blend was added and compressed over the first layer. The tablet press applied the necessary force to form a stable bilayer tablet.
5. Quality Control: The final tablet was tested for uniformity, hardness, weight variation, and release characteristics, ensuring it met the required specifications for both drugs.

Top of Form

Bottom of Form

Formulations of different Batches

EVALUATION PARAMETERS OF TABLET

1. Weight Variation

By weighing 20 tablets separately, calculating the average weight, and comparing the weights of each tablet to the average, the IP offers the weight variation test. 250 mg or more +/- 5% is the limit.

2. Thickness or Friability and Hardness

Thickness  refers to the measures of the distance from one surface of an objects to the opposite surface typically measured in unit of length.

A sample of pre-weighted tablets is put in a friabilator and spun for four minutes at 100 revolutions. Tablets that lose less than 1.0% of their weight after testing are usually regarded as acceptable.

Using a tablet hardness tester, a force is applied to the tablet until it breaks, and the result is given in units like kg/cm².

Fig 2. Hardness, friability, Thickness

3. Disintegration Time

The tablet disintegration time procedure is used to evaluate how quickly a tablet breaks apart in a liquid environment.

1. Apparatus: A disintegration tester with six tubes was used to hold the tablets. The tubes were immersed in a basket that moved up and down in a water bath.
2. Conditions: The water bath's temperature was kept at 37°C (±2°C).to simulate body temperature.
3. procedure

• Each tube contained one tablet.
• The basket was raised and lowered at a standard speed (usually 30 times per minute).
• The tablet was considered disintegrated when it broke into smaller pieces or passed through the mesh at the bottom of the tube.

4. Timing: The disintegration time was determined by measuring and recording the amount of time it took for the tablet to completely dissolve.
5. Acceptance Criteria: The tablets were required to disintegrate within a specified time.

Fig 3. Disintegration time of tablet

4. Dissolution Test

1. Setup: 900 mL of phosphate buffer solution with a pH of 6.5 was added to the dissolution vessel,  and the temperature was adjusted to 37°C.
2. Tablet Placement: One tablet was placed into the vessel.
3. Rotation: The basket or paddle apparatus was set at a specified speed of 50 rpm.
4. Sampling: At defined intervals (e.g., 30 min, 60min, 90min), samples were withdrawn and filtered.
5. Analysis: The drug concentration was measured using UV spectrophotometry.
6. Acceptance: Drug release was checked to ensure it met the required percentage.

Fig 4. Dissolution Test

Fig 5. % DR vs Time by UV spectroscopy