Parecoxib Mucoadhesive Tablets For Pain And Inflammation Biology Essay

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The main purpose of present study was to develop mucoadhesive tablets of Parecoxib to relive patients from pain and inflammation. The mucoadhesive tablets were prepared by direct compression technique. The drug- excipient compatibility studies were performed by Fourier Transform Infrared spectroscopy (FTIR). Physicochemical characteristics and in vitro drug dissolution tests were performed. The in vitro drug release pattern and the dissolution data was treated with mathematical modeling Accelerated stability studies were also carried out to the optimized formulation (F-5). The DSC and FTIR studies revealed that drugs were compatible with the polymer used. The optimized formulations were found to have good physicochemical and in vitro release properties. The in vitro dissolution data was perfectly fitting to zero order and the release of drug from the formulation followed Higuchi's release. The accelerated stability studies revealed that the tablets retain their characteristics even after stressed storage conditions. From this study it was concluded that Parecoxib mucoadhesive Tablets is a good combination for relieving pain and inflammation.

Keywords: Parecoxib, mucoadhesive tablet, evaluation.


Parecoxib, a non-steroidal anti-inflammatory drug (NSAID) that exhibits anti-inflammatory, analgesic and antipyretic properties was chosen as a model drug due to its high first pass metabolism2. It undergoes both P450 and non-P450 dependent (Glucuronidation) metabolism3. The mechanism of action is believed to be due to inhibition of Prostaglandin synthesis primarily through inhibition of cyclooxygenase-2 (COX-2).

Mucoadhesive Parecoxib tablets were prepared by using Sodium Carboxy methyl cellulose, Hydroxy Propyl Methyl Cellulose, Carbopol-934P and Poly Vinyl Pyrrolidone4-6. There is no availability of Parecoxib mucoadhesive tablets commercially. So an attempt has been made to develop a sustained release mucoadhessive formulation of parecoxib.



Parecoxib was obtained from Dr. Reddy's laboratories (Hyderabad, India). Hydroxy propyl methyl cellulose (HPMC) K4M, Carbopol-934P, Sodium Carboxy Methyl Cellulose-H, Poly vinyl Pyrrolidone-K30, Saccharin sodium, Amaranth, Ethanol and magnesium stearate were procured from SD fine chemicals, Mumbai, India and all other ingredients used were of analytical grade.

Drug-excipient compatibility studies

Fourier Transform Infrared Spectroscopic (FTIR) analysis

The FTIR spectrums of Parecoxib and Formulation (F-5) blend were studied by using Fourier Transform Infrared (FTIR) spectrophotometer (Perkin Elmer, spectrum-100, Japan) using the KBr disk method (5.2510 mg sample in 300.2502 mg KBr). The scanning range was 500 to 4000 cm-1 and the resolution was 1 cm-1. This spectral analysis was employed to check the compatibility of drugs with the polymers used.

Preparation of mucoadhesive Tablets7-10

Mucoadhesive tablets were prepared in 3 steps

a) Preparation of Core Layer's Mixture:

Parecoxib, HPMC, Carbopol-934P, Sodium Carboxy Methyl Cellulose-H, Poly vinyl Pyrrolidone-K30 and Magnesium stearate were mixed well by using glass mortar and pestle. This mixture was used for the preparation of core layer of the tablet. The composition of core layer was represented in Table 1.

b) Preparation of Backing Layer's Granules:

Carbopol-934P, Poly vinyl Pyrrolidone, Magnesium stearate, Saccharin sodium were mixed well using glass mortar and pestle. In a separate glass beaker, solution of Amaranth was prepared using ethanol as a solvent. By gradually adding the color solution to a dry mixture; a wet mass/lump was prepared. Peppermint oil was added to this lump and mixed properly. Then this lump was passed through the sieve # 40. Then wet granules were dried in a Hhot Air Oven at a temperature 500C for 20 min. To this dried granules, magnesium stearate lubricant was added. These granules were used for the preparation of backing layer of the tablet. The composition of backing layer was represented in Table No. 2.

c) Compression:

For this purpose an I.R. hydraulic press and Die Punch Set having diameter of 10mm was used. Firstly, the mixture of drug and polymers (weighed quantity-150mg) was compressed using a pressure of 50kg/cm2 for 5 s. Then upper punch was removed and then granules of backing layer (weighed quantity -75mg) were added over the first layer and compressed at a pressure of 200kg/cm2 for 15 s. By this way, the bilayer tablet was prepared.

Physical evaluation of tablets10-17


The thickness of the tablets was determined using a screw gauge (ISC Technologies, Kochi, India). 5 tablets from each batch were used and the mean values were calculated.

Uniformity of Weight Test:

20 tablets of each formulation were weighed using an electronic balance (YPX202N, China) and the test was performed as per the official procedures.

Hardness test:

The hardness of the tablets was measured using Monsanto tablet hardness tester (MHT 51, China). It is expressed in kg/cm2. Three tablets were randomly picked and analyzed for hardness. The average and standard deviation values were also calculated.

Friability test:

The friability of tablets was determined using Roche Friabilator (Campbell Electronics, Mumbai, India). The friabilator was operated at 25 rpm for 4 min (totally 100 revolutions). The % friability was then calculated by the following equation.

F= Winitial - Wfinal / Winitial X 100


F= friability (%), Winitial = initial weight and Wfinal = Final weight

Uniformity in drug content:

The formulated tablets were tested for uniformity in Parecoxib contents by using UV/ Visible spectrophotometer (Elico SL 210, India) 243 nm for Parecoxib.

Surface pH

The surface pH of the mucoadhesive tablets was determined to find out the possibility of any side effects when swallowed. An acidic or alkaline pH may cause irritation to the mucosa. The tablet was allowed to swell by keeping it in contact with 1 ml of distilled water (pH 6.5 ± 0.05) for 2h at room temperature. The pH was measured by using digital pH meter (PHS-25, China).

Moisture absorption studies of mucoadhesive tablet

A 5% w/v solution of Agar prepared in hot water and transferred into petri dishes and allowed to solidify. Five pre weighed tablets from each formulation were placed in vacuum oven overnight to remove moisture and laminated on one side with a water impermeable backing membrane. The tablets were placed on the surface of the agar and incubated at 370C for 1 h. Then the tablets were removed and weighed and the percentage of moisture absorption was calculated by using the following equation.

% Moisture absorption = {(final weight - initial weight)/initial weight} x100

Mucoadhesive Force Measurement

Mucoadhesive force measurement of tablets was done by modifying balance method. The right pan was replaced with a glass beaker container and on the left side beaker with a copper wire. Teflon block of 1.5 cm diameter and 3 cm height was adhered strongly with the glass beaker. The two sides were then adjusted, so that the left hand side was exactly 5 g heavier than the right. Stick the stomach on the teflon block with help of the cynoacrylate glue and fill the beaker with acidic buffer till the tissue remains in a moist condition. Stick the tablet to beaker and put on the tissue for 15 min, later add water slowly into right beaker until the tablet detaches12. Weigh the water required for the tablet detachment. Calculate Actual weight for detachment and force of adhesion in dynes by following equation.

Actual weight for detachment (W) = weight for detachment (g)

Matrix Erosion

Each tablet weighed (W1) were immersed in a phosphate buffer pH 6.8 for predetermined time (1, 2, 4, 8 and 12 h). After immersion, tablets were wiped off by the excess of surface water by the use of filter paper. The swollen tablets were dried at 60°C for 24 h in an oven and kept in a desiccator for 48 h prior to be reweighed (W2). The matrix erosion was calculated using the following equation.

Matrix Erosion = (W1 - W2)/ W1- 100

Swelling behavior of matrix tablets

The swelling behavior of formulation F-1, F-2, F-3, F-4 and F-5 were studied11. One tablet from each formulation was kept in a Petri dish containing phosphate pH 7.4. At the end of 2 h, the tablet was withdrawn, kept on tissue paper and weighed, repeated for every 2 h till the end of 12 h. The % weight gain by the tablet was calculated by following equation.

S.I = {(Mt-M0) / M0} X 100

Where, S.I = Swelling Index, Mt = Weight of tablet at time 't' and

M0 = Weight of tablet at time 0.

In vitro Dissolution Studies18-20

The dissolution of the mucoadhesive tablets were performed using USP XXIII dissolution apparatus (paddle method) using 500 ml of phosphate buffer (pH 7.4) as the dissolution medium, which was maintained at 37±0.50C and stirred at 50 rpm. Tablet was glued with Cyanoacrylate adhesive (Evobond) from backing layer side to the glass slide and it was placed at the bottom of jar of dissolution apparatus to avoid movement of tablet. Aliquots of 5ml of samples were withdrawn with a bulb pipette at different time intervals of 30, 60, 120, 180, 240, 300 and 360 min and replaced with equal volume of phosphate buffer (pH 7.4) at each withdrawal, filtered it through Whatmann Filter Paper No.1. The samples were then analyzed using double beam UV visible spectrophotometer (Elico SL 210, India) at 243 nm for Parecoxib. The cumulative amount of drug released at various time intervals was calculated.

Accelerated Stability Studies

To assess the drug and formulation stability, stability studies were done according to ICH and WHO guidelines. Optimized formulation (F-5) was sealed in aluminum packaging coated inside with polyethylene, and then kept in stability chamber maintained at 450C and 75% RH for 3 months. At the end of studies, samples were analyzed for the drug content, in-vitro dissolution, floating behavior and other physicochemical parameters


Compatibility studies

The FTIR spectra of Parecoxib showed characteristic peaks at 3441.05 (3300-3500) (N-H), 2909.68 and 2805.61 (2850 - 3000) (C-H), 2805.61 (3300 - 2500 (O-H), 1521.66, 1447.00 and 1405.77 (1350 -1550) (N=O), 1217.98, 1153.91, 1127.73 and 1080.53 (1220 -1020) (C-N), 1283.52 and 12487(1000 -1300) (C-O) (Figure 1)

The formulation showed characteristic peaks at 3439.40 (3300-3500) (N-H), 2942.54 (2850 - 3000) (C-H), 2739.88 (3300 - 2500 (O-H), 1485.61, 1446.91 and 1387.02 (1350 -1550) (N=O), 1035.13, (1220 -1020) (C-N), 1156.96 (1000 -1300) (C-O) (Figure).

Evaluation of tablets

Average weights of the formulated tablets were ranged from 200±2.562 to 202±6.856 mg. The thickness of the formulated tablets were ranged from 8.0±0.139 to 8.2±0.125 mm, indicates uniformity in weight and thickness. The hardness of the formulated tablets were ranged from 6.8±0.06 to 8.9±0.08 kg/cm2, which was more than 5 kg/cm2 and the weight loss on friability was ranged from 0.11±0.03 to 0.85±0.05 %. The hardness and friability results revealed that the formulated tablets have good mechanical strength, which helps in maintaining the rigidness of tablet during handling and transport. All these physical and mechanical properties of formulated tablets showed in Table No.3. The formulated tablets showed good Swelling behavior and showed in Figure 4.

The swelling index increases by increasing the contact time as the polymers gradually absorbs the water due to hydrophilic nature with resultant swelling.

The surface pH was ranged from 6.68 ± 0.15 to 7.06 ± 0.54. The percentage water absorption was ranged from 48.25 ± 0.88 to 49.99 ± 1.22%. The formulated tablets showed good mucoadhesive strength which was ranged from 19.21 ± 4.52 to 23.68 ± 2.59. The mucoadhesion strength increases as the concentration of polymers increased. The percentage of Parecoxib in formulated tablets was ranged from 99.79±4.65 to 99.98±4.69% indicating the uniformity of drug content in formulation All these values were shown in Table 4.

The matrix erosion of formulated tablets after 2, 4, 6, 8 and 12th hour was shown in Table 5. The plots result from in-vitro dissolution study was shown in Figures 5 and 6. The optimized formulation (F-5) was tested for drug content, Surface pH, mucoadhesion strength and Swelling Index before and after accelerated stability studies. The study proved that the formulations retain their characteristic parameters before and after accelerated stability studies. The values were shown in Table 6.


This study revealed that Parecoxib mucoadhesive tablets are a good candidate for treatment of patients with pain and inflammation.