FORMULATION AND EVALUATION OF FAST DISINTEGRATING TABLET OF GLIMEPIRIDE

Objective: Glimepiride is the third generation sulphonylurea agent, used for the treatment of type II diabetes mellitus. Glimepiride is given once daily in doses from 1-4 mg. The objective of the present study was to formulate and evaluate the fast disintegrating tablets of Glimepiride. Method: The fast dissolving tablets of glimepiride were prepared by direct compression method by using different disintegrating agents. The drug and the excipients were evaluated for angle of repose, bulk density, tapped density, carr’s index and hausner’s ratio for the determination of flow property of the powder. The formulated tablets were evaluated for thickness, hardness, friability, wetting time, water absorption ratio, and dissolution and disintegration time. Result: Fast disintegrating tablets were successfully prepared by direct compression method. The disintegration time was less than 1 minute which is acceptable. The obtained results clearly indicated that the prepared tablets of glimepiride were fast disintegrating. Conclusion: The fast disintegrating tablets of glimepiride are prepared with disintegrating time less than 1 minute, this will help in future for further improvement of dosage and formulation and will help to control immediately the rise glucose level of chronic diabetic patients.


Melting Point
Reduce the substance to a very fine powder and

Tapped Density
Tapped density of the powder was measured by pouring gently some amount of sample through a glass funnel into a graduated cylinder. The cylinder was tapped from height of 2 inches until a constant volume was obtained (100 taps). Volume occupied by the sample after tapping was recorded and tapped density was calculated.

Angle of Repose
The angle of repose of the powder was determined by fixed funnel method. The powder was poured through a funnel that can be raised vertically until a maximum cone height (h) was obtained. Radius of the heap I was measured. It is expressed in gm/ml. By applying following formula, angle of repose was Friability test: Ten tablets were randomly selected and weighed them. Friability was measured using Roche friabilator. Pre-weighed tablets were placed in a plastic chambered friabilator attached to a motor revolving at a speed of 25 rpm for 4 min. The tablets were then de-dusted, accurately reweighed, and jcponline.pk percentage loss in weight (friability) was calculated [14].

Content Uniformity
The tablets were kept in 100ml volumetric flask containing phosphate buffer pH 4.4 for 24hrs.When the tablets were completely dissolved the solution was centrifuged. After centrifugation the supernatant was dissolved. Absorbance was measured spectrophotometrically at 228 nm. Dilution was made using phosphate buffer (pH 7.8) as per requirement [12].

Wetting Time and Water Absorption Ratio
It is related with each other and performed in the same manner. The tissue papers were placed in a petri dish by folding it into five circular form in a 10 cm diameter. Petri dish containing ten milliliters of water with 0.5 % nigrosine, a water-soluble dye, was added to the petri dish. The dye solution was used to identify complete wetting of the tablet surface. The Tablet was carefully placed on the surface of the tissue paper in the center of the petri dish at 25 °C.
The time required for water to reach the upper surface of the tablets and to completely wet them was noted as the wetting time. It was carried out in six times. Wetting time was recorded using a stopwatch and presented as mean standard deviation [11].

Dissolution Test
The invitro drug release study was performed using USP dissolution apparatus (Paddle Apparatus) Dissolution study was carried out for 12 hours.
Phosphate buffer having pH 7.8; 900ml was used as dissolution media. Samples of each 5ml were withdrawn after everyone hour for a period of 12h.Volume in dissolution vessel was kept constant by equal replacement with fresh media. The samples were collected in test tubes after filtration through filter paper. The amount of the drug in the aliquots was quantified by taking absorbance of the sample at 288 nm spectrophotometrically, using phosphate buffer pH 7.8 (dissolution media) as the blank [7].

Disintegration Test
The disintegration of tablets was determined using a USP disintegration testing apparatus type II with pH 6.8 phosphate buffer as a disintegrating medium. The medium was maintained at 37±0.5 °C throughout the test. Six tablets were placed into an apparatus and disintegration time was recorded. Measurements were carried out in replicates of six and mean standard deviation were recorded [7].

RESULTS
Different tests were performed on powder material before compression of tablet.

Pre-compression Parameters
Physical appearance of the powder material was solid (amorphous). Melting point determined by capillary method was 207 ˚C. Bulk density and tapped density was found to be 0.499 and 0.898 respectively. Carr's index and Hausner's ratio was found to be 16 % and 1.16 respectively. Angle of repose was measured as 33.

Post compression Parameters
In weight variation test, the standard deviation was 7.3% which is within acceptable range.
After applying force, the hardness limit of all prepared tablets was 2.6-3.5 kg/cm 2 that is acceptable. The mean of the thickness of the tablets was±5% that is somehow acceptable for fast dissolving tablets. Friability percentage was 0.98% that is an indication of good mechanical resistance of the tablets.
Water absorption ratio and wetting time, which are important criteria for understanding the capacity of disintegrants to swell in the presence of little amount of water were found to be in the range of 64-84% and jcponline.pk 22-94 seconds respectively. Drug content was found to be in the range of 96 to 98%, which is within acceptable limits. Disintegration time was less than 1 minute that is in acceptable limits for fast disintegrating tablets. In-vitro dissolution studies showed that more than 50 % of the drug was released from the formulation within 5 min.
FTIR studies did not indicate any excipient incompatibility, either during mixing or after compression.