DEVELOPMENT, FORMULATION AND EVALUATION OF MECLOFENAMATE FAST DISSOLVING TABLETS

The demands for fast dissolving tablets have received ever increasing day by day during the last 10-15 years for the onset of action. In the present study, the effect of superdisintegrant was compared with synthetic super disintegrants and other conventional super disintegrants in the of fast dissolving tablet formulation of Meclofenamate. Meclofenamate is an antihypertensive drug and in case of hypertension immediate treatment is required so the proposed investigation is totally based to provide the suitable treatment for hypertension. In the present work 9 formulations of Fast dissolving tablets of Cilnidipine were prepared by using Synthesized Co-proceed was evaluated and compiles with the official standards, parameters and specifications. Various formulations were prepared using four different superdisintegrant namely- kyron T-304, sodium starch glycolate, cross carmelose sodium with three concentrations (2%, 4%, 6%) by direct compression method. The blend was evaluated for pre-compression parameters like Angle of repose , bulk density , tapped density , and then tablet evaluated post-compression parameters like thickness , Formulation A8 showed the lowest disintegration time and in-vitro dissolution studies recorded that formulation A8 showed 98.64% drug release at the end of 3 minutes. The best formulations were also found to be stable and optimized formulations were subjected to the stability studies as per ICH guideline and standards.


Introduction
The tablet is most widely used dosage for because of its convenience in term of self-administration, compactness, accurate dosage and ease in manufacturing. Over this one drawback of conventional tablet is difficulty in swallowing by pediatric and geriatric patients. 1 To beat these issues the scientists have developed novel drug delivery system that known as fast dissolving tablet. The fast dissolving tablets that dissolving in few seconds in the mouth when they come with contact saline without requirement of additional water. The advantage of FDT (Fast dissolving tablet) is onset of action, higher patient acceptance, and increased bioavailability. [2][3][4] Meclofenamate Sodium is the sodium salt form of meclofenamate, an anthranilic acid and nonsteroidal anti-inflammatory drug (NSAID) with anti-inflammatory, antipyretic and analgesic activities. Meclofenamate sodium inhibits the activity of the enzymes cyclo-oxygenase I and II, resulting in decreased formation of precursors of prostaglandins and thromboxanes. Drug delivery via the oral mucosa is a promising route, when one wishes to achieve a rapid onset of action or improved bioavailability for drugs with high first-pass metabolism. Thus, there is a growing interest in developing alternative dosage forms, i.e. orally fast disintegrating strip, which allow a rapidly dissolving drug to absorb directly into the systemic circulation through the oral mucosa These kinds of dosage forms are also convenient for children, elderly patients with swallowing difficulties, and in the absence of potable liquids. However, in addition to formulation considerations, the properties of the active compound have to be appropriate in order to achieve drug delivery into systemic circulation after intraoral administration.

Material and Method
Meclofenamate was received as gift sample by Pro Lab Marketing, Mumbai, Magnesium stearate used were procured from Reckon animal health care, Jaipur , Lactose used was procured from Rescue laboratories, Jaipur, Kyron T-314 was gifted by Corel PharmaChem, Ahmadabad,

Angle of Repose (θ):
Angle of repose is defined as, the maximum possible angle between the surface of the pile of the powder and the horizontal plane of the powder. When more quantity powder is added to the pile, it slides down, until the mutual friction of the particles producing a surface angle θ, is equilibrium with the gravitational force. [15][16][17] The angle of repose was determined by the funnel method suggested by the scientist Newman. Angle of repose is determined by the following formula Tan θ = h/r θ = Tan -1 h/r Where θ = Angle of repose r = Radius of the cone h = height of the cone Bulk Density: Density defined as weight per unit volume. Bulk density is defined as the mass of the powder is divided by the bulk volume of powder and is expressed as gm/ cm 3 .The bulk density of a powder primarily depends on its, particle shape, particle size, distribution and the tendency of particles to adhere together. There are two types of bulk density. [18][19][20][21]

Low Bulk Density
The particles are pack in such a way so as to leave large gaps between their surfaces resulting up in light powder of low bulk density.

High Bulk Density
Here the smaller particles shift between the large particles resulting in heavy powder of high bulk density

Tapped Density (DT):
It was the ratio index of total mass of the powder to tapped volume of the powder. Volume was reported by tapping the powder for 500 times and the tapped volume was recorded, if the difference between these two volumes was less than 2%. If it more than 2%, then tapping was continued for 750 times and tapped volume was noted. Tapping was continued until the difference between volumes was less than 2% in bulk density apparatus. It was expressed in g/ml and was given as following, DT= M/Vt Where, M is the mass of powder Vt is the tapped volume of the powder. [22][23][24] Carr's Index (Or) % Compressibility: Carr's index indicates powder flow properties. It is expressed by percentage and is given by: I=DT−Db/DT×100 Where, DT denotes the tapped density of the powder And Db is the bulk density of the powder. [25][26][27][28] Hausner Ratio: Hausner ratio is an indirect index of ease of powder flow properties. It is calculated by the following formula: Hausner ratio=Dt/Db Where, Dt show the tapped density. Db is the bulk density. Lower hausner ratio (<1.25) indicates better flow properties than higher ones (>1.25)

Evaluatation of Tablet:-
All prepared tablets of Aceclofenac were evaluated for the following parameters as per IP guideline and standards for all the calculations are represented in the table No.3 Weight Variation:-Twenty tablets of Aceclofenac formulation were selected randomly from each of the formulation and weighted individually using Citizen Digital Balance for their weight data. The average weight of the tablets as well as percentage deviation was calculated. [29][30][31] Hardness:-Hardness of the Aceclofenac HCL tablet was measured with the tablet hardness testing apparatus known as Monsanto tablet harness tester. 32

Thickness:-
The thickness of the tablet was measured in mm by the Vernier Calipers for all the designed formulation batches.

Friability:-
The friability of the Aceclofenac HCL tablet, a sample of twenty tablets was measured using USP type Roche Friabilator. The tablets were dusted reweighed and percentage weight-loss was calculated. % Friability = Initial Weight−Final Weight * 100/ Initial Weight

Water Absorption Ratio:
A piece of tissue paper (12 cm X 10.75 cm) folded twice was placed in small Petri-plate (ID = 6.5 cm) containing 10 ml of water. A tablet was placed on the paper and time for complete wetting of the tablet was measured in seconds. Three trials for each batch were performed and the standard deviation was also determined. The wetted tablet was weighed and water absorption ratio R, was determined by following equation

R = {(Wa -Wb) / Wa} × 100
Where, Wa and W b were weights of the tablets after and before study. [33][34][35] Wetting Time A piece of tissue paper (12cmX10.75cm) folded twice was placed in a small Petri dish (ID = 9 cm) containing 6ml pH 6.8 phosphate buffer, A tablet was placed on the paper and the time taken for complete wetting was noted. Three tablets from each formulation were randomly selected and the average wetting time was noted.
Disintegration Study:-Disintegration time study was carried out by selecting 6 tablets of Aceclofenac and performed disintegration test (Lab India) using 900 ml distilled water at temperature (37 0 C±2 0 C) 36

Dissolution Study:-
The In-vitro for the dissolution study was carried out in the USP (United state pharmacopeia) dissolution test apparatus type 2 known as Paddle dissolution apparatus, used phosphate buffer as dissolution medium as 900 ml containing PH 6.8 was taken in vessel and the temperature maintained at 37±0.5 0 C. The speed of the paddle was set at RPM 50, then 5 ml dissolution medium was withdrawn and the same amount (5ml) of fresh medium was replenished to the dissolution medium.   Mannitol  20  17  14  20  17  14  20  17  14  Lactose  21  21  21  21  21  21  21  21  21  TOTAL  150  150  150  150  150  150  150  150  150 Result and Discussion Analytical Profile of Meclofenamate: The DSC thermogram of Meclofenamate is shown in Figure 1. The DSC thermogram of Meclofenamate showed sharp peak at 279 0 C. The identity of a compound was confirmed by comparison with that of an authentic sample and verification of the presence of functional groups in an unknown molecule was done by IR spectra. The IR spectra obtained was elucidated for important chromophore groups. The IR spectra showed peaks at 3311, 2924, 2854, 1651, 1511, 1163 and 551 cm -1 . The various peaks are depicted below.     Table 5. The maximum solubility was found in DMSO and least in water. Partition coefficient of Meclofenamate in Phosphate buffer pH 7.4 was found to be 3

Characterization of Fast Dissolving Tablets of Meclofenamate
On the characterization of the drug free tablet the best formulations were selected and the drug Meclofenamate was incorporated in these formulation. The characterization of mixed blend done for the flow property of powder that are bulk density, tapped density, angle of repose, Compressibility index, Hausner's ratio were shown in Table 5. The prepared drug tablets were evaluated as similar as the drug free tablets. After compression of powder the tablet were evaluated for physical organoleptic characteristics like colour, odour, taste, diameter, Thickness, Hardness, Friability, dispersion time, Disintegration time, wetting time. All the formulations were exhibit in white colour, odorless, convex in shape with smooth surface with zero defects. The average weight of the prepared tablet was found 145.07 to 154.05 mg. The thickness of the tablet was found 3 mm. The diameter of the tablets was found to be 4 mm. The hardness of the prepared tablet varied from 3.01 to 3.20 Kg/cm 2 . Which have satisfactory strength to withstand the mechanical shocks. The friability of all the formulation was found to be less than 1.0 %. The results shows resistance to loss of weight indicates the tablet's ability to withstand abrasion in handling, packaging and shipment. The disintegration time of the tablets was varied from 30 to 69 seconds. The in vitro swelling time of all the formulations were varied between 14 to 22 seconds.