Formulation Development and In-vitro Evaluation of Mouth Dissolving Tablets of Celecoxib Employing Distinctive Proportion of Disintegrating Agents

Article Information Received 26 Feb 2014 Received in revised form 02 April 2014 Accepted 05 April 2014 Abstract In present study we planned to formulate and evaluate mouth dissolving tablets of Celecoxib using superdisintegrants agents namely Crospovidone and Sodium starch glycolate in various ratios. The mouth dissolving tablets were prepared by direct compression method using Crospovidone and Sodium starch glycolate. Tablets blends were evaluated for loose bulk density, tapped bulk density, compressibility index and angle of repose, shows satisfactory results. The compressed tablets were then evaluated for various physical tests like thickness, friability, hardness, weight variation, wetting time, water absorption ratio and disintegration test by using standard procedures. The results of all these tests were found to be satisfactory. The in-vitro dissolution study was carried out for 14 min using paddle method in phosphate buffer (pH 6.8) as dissolution media. The data of in-vitro dissolution of tablets revealed that 76 to 100% of drug release from various formulations at 14 min. The formulation C7 exhibited better results as compared to other formulations.


Introduction
The oral route of drug administration is mostly used and acceptable comparable to other dosage form which produces systemic delivery of therapeutic agents.The low cost of oral administration enhance it demands.Among oral route of administration, the tablets are widely used because of their special properties such as suitability to selfadministration, improved stability, accurate dosing, ease of handling, versatility with respect to type and dose of the drug, and suitability to scale up.But sometime tablets fails to prove it's useful in some circumstance.The elderly patient face problem in taking conventional oral dosage forms like solutions, suspensions, tablets, capsules, due to hand tremors and dysphagia.The pediatric patients face difficulties in swallowing of tablets which leads to poor compliance.The mentally ill, developmentally disabled patients, and patients who are uncooperative or who are suffering from severe nausea gets problems in taking conventional oral dosage form [1][2][3][4] .
However, this form of dosage has some limitation like motion sickness, sudden episodes of allergic attacks or coughing and unavailability of water, but one important drawback is 'dysphagia' or difficulty in swallowing 5 .Additionally, there are many instances where tablets may not suit the given indication.Above mentioned task can be overcome by substituting conventional tablets and capsules with mouth dissolving tablets.
Celecoxib is the selective COX-2 inhibitor, it belong to nonsteroidal anti-inflammatory category.It has highly demand in the healing of osteoarthritis, rheumatoid arthritis and dysmenorrhea in adult patients.Celecoxib tablets have rate limiting steps in the process of drug absorption due to its poor water solubility properties.
Additionally, it displayed poor absorption in large intestine.
Conventional Celecoxib tablet available in the market are not suitable for urgent response of drug where quick onset of action of drug is required.The rapidly disintegrating tablets in oral cavity can be swallowed with a small amount of water or saliva [6][7][8][9] .Hence, an attempt was made to improve the dissolution of Celecoxib through the formulation of mouth-dissolving tablets with appropriate mechanical strength, which would disintegrate in oral cavity, in less than 30 seconds, and would provide an immediate relief to patients due to its faster dissolution in gastrointestinal tract.

Preparation of mouth dissolving tablets
Tablets of Celecoxib were prepared by direct compression method.
All the formulation ingredients mentioned in formulation table 1 were weighed accordingly and mixed in a mortar and pestle.This powder blend was then allowed to dry for few moments and then again mixed well and passed through sieve no 60.Then blend were used for further processing.

Evaluation of pre-compression characteristics of powder
blend [10][11][12] Powder blend prepared were evaluated for various rheological properties like bulk density, tapped density, Hausner's ratio, angle of repose by using standard procedures.All these properties were carried out in triplicate (n=3) and average values were reported.

Bulk density
Bulk density was determined by placing the powders blend in a measuring cylinder and the total volume is noted.The weight of powder bed was determined by using digital weighing balance.Bulk density was calculated using the following formula: Bulk Density = Weight of the powder / Volume of the powder Where, h = height of heap of granular bed, r = radius of heap of granular bed.

Hausner's ratio
It is expressed in percentage and is expressed by

H=Dt/Db
Where Dt is the tapped density of the powder Db is the bulk density of the powder.

Evaluation of compression characteristics of mouth dissolving
tablets [13][14][15][16] The prepared tablets were evaluated for their thickness, friability, hardness, weight variation and dissolution test by using standard procedures.

Weight variation test
20 tablets are taken and their weight is determined individually and collectively on a digital weighting balance.The average weight of one tablet is determined from the collective weight.Note more than 2 of the individual weights may deviate from the average weight by more than the percentage deviation given in the monographs and none should deviate by more than twice that percentage given in the monographs.

Thickness test
The tablets were evaluated for their thickness using a venirer caliper measured in terms of micrometer.Averages of three readings were taken and the results were tabulated (n = 3)

Hardness test
Prepared tablets were evaluated for their hardness by using Monsanto hardness tester.The hardness was measured in terms of kg/cm 2 .Triplicate readings were taken and average was determined.

Friability test
Roche friabilator was used for testing the friability of the tablets.For this test, 20 tablets were weighted accurately and placed in the friabilator chamber and rotated at 25 rpm for a period of 4 min.
Tablets were again weighted and the percentage weight loss was determining by using formula given below.
Where, W1= Weight of tablet before test W2 = Weight of tablet after test.

Wetting time
A piece of tissue paper folded twice was placed in a small Petri dish containing 6 ml of purified water, then a tablet was placed on the paper and the time required for complete wetting was measured.
Wetting time corresponds to the time taken for the tablet to disintegrate when placed gently on the tissue paper in a Petridish.
Less wetting time indicates more porous tablets.

Water absorption ratio
A piece of tissue paper folded twice was placed in a small petri plate containing 6 ml of distilled water.A tablet was put on the paper and time required for complete wetting was measured.The wetted tablet was then weighed.Water absorption ratio R was calculated using equation.R = 100 {(Wa -Wb)/Wb} Wa = weight of the tablet after water absorption Where, Wb = weight of the tablet before water absorption

In-vitro disintegration time
The process of breakdown of a tablet into smaller particles is called as disintegration.The in vitro disintegration time of a tablet was determined using disintegration test apparatus as per IP specifications.Place one tablet in each of the 6 tubes of the basket.
Add a disc to each tube and run the apparatus using pH 6.8 (simulated saliva fluid) maintained at 37±2 °C as the immersion liquid.The assembly should be raised and lowered between 30 cycles per minute in the pH 6.8 maintained at 37±2 °C.The time in seconds taken for complete disintegration of the tablet with no palpable mass remaining in the apparatus was measured and recorded

In-vitro drug release study
In vitro release study was performed using tablet dissolution test apparatus USP XXIII, apparatus I.The dissolution medium consists of 900 mL phosphate buffer pH6.8 maintained at 37 ± 1°C rotated at 50 rpm.At different interval of time 10 mL sample was withdrawn and replaced with fresh medium.10 mL sample was diluted to 100 mL phosphate buffer pH 6.8, the aliquots were assayed spectrophotometrically at 252 nm for Celecoxib.

Evaluation of pre-compression characteristics of powder blend
The powders were evaluated for bulk density, tapped density, Hausner's ratio and angle of repose and consistency in data obtained as indicated by their standard deviation values shown in table 2.
Bulk density and tapped density of different formulations were calculated.The result of bulk density range from 0.473 to 0.483 and tapped density from 0.467 to 0.513.Hausner's ratio was found to be in between 1.12 to 1.19; and Compressibility index from 11.39 to 14.09.Angle of repose showed good to excellent flow properties of the powdered blend (Table 2).
The tablet dimension includes diameter and thickness of tablets.
Thickness of all formulations was found to be between 2.25 to 2.84 (Table 3).No significant difference was observed in the thickness of individual tablet from the average value.No significant difference was observed in the weight of individual tablets form the average weight.
From table 3 it has been observed that tablet weights of all bathes were found with in recommended USP limits, between 218 ± 1 mg.
Hardness of tablets of all batches are in between 3.14 to 3.72 (Kg/cm 2 ) which is acceptable limits, which shows in the literature.
Friability of all the formulation showed % friability less than 1% that indicates ability of tablets to withstand shocks, which may encountered.The data of uniformity of content which was performed by UV spectroscopy indicated that tablets of all batches had drug content within USP limits i.e. between 97.43 to 99.34%.In guidance of industrial scientist different parameter of tablet like flow property, dimension hardness, drug content etc. were studied which results in successful trials.
The wetting time and water absorption ratio were found to be 13.25 to 27.38 seconds and 84.73 to 40.62 seconds (Table 4), respectively.The disintegration time of mouth dissolving tablets ranges from 18.16 to 31.84 seconds (Table 4).
From above result it has been observed that C7 formulation exhibited excellent wetting time, water absorption ratio and disintegration time as compared to other formulations.Moreover the C8 formulation exhibited lowest wetting time and disintegration time; and highest water absorption ratio.This parameter enhances due to gelling and its subsequent viscosity producing effects.

2 . 2 . 5
Tapped density was determined by taking the dried powders in a measuring cylinder and measures the volume of powders after 100 tapping's and take weight of the total powders.Tapped Density = Weight of the powder / Tapped Volume of the powder Angle of repose Angle of repose was determined by measuring the height and radius of the heap of the powder bed.A cylindrical two side open tube of 6 cm length is place on graph paper.Powders are placed in the tube and slowly removed the tube vertically.With the help of scale the height and radius of the heap were measure and note.θ= tan -1 h / r

Figure 1 displayed
Figure 1 displayed in-vitro dissolution of tablets, it revealed that 76 to 100% of drug release from various formulations.The 50% of the drug was released from the C7 and C8 within 4 minutes.The rapid drug dissolution might be due to easy breakdown of particle by superdisintegrant action.From in vitro dissolution data, it was

Fig 1 :
Fig 1: In-vitro drug release profile of Celecoxib mouth dissolving tablets

Table 3 : Evaluation of Celecoxib mouth dissolving tablets
*Average of three times measure

Table 4 : Evaluation of wetting time, water absorption ratio and in-vitro disintegration time of mouth dissolving tablets Formulation Wetting time (sec) Water absorption ratio (sec) In-vitro disintegration time (sec)
Value shown in tables is mean of three determinations