Abstract

Objective of this study was to formulate directly compressible fast dissolving tablets of Gliclazide with sufficient mechanical integrity, content uniformity, and acceptable palatability to assist patients of any age group for easy administration and to show the effect of maximum concentration (10 %) of different combination of superdisintegrants such as crospovidone, croscarmellose sodium, and sodium starch glycolate on disintegration time. Tablets were evaluated for weight variation, thickness, hardness, friability, taste, drug content, in vitro disintegrating time and in vitro drug release. Other parameters such as wetting time, water absorption ratio were also evaluated. The disintegration time of the optimized C5 batch was found to be 24.7 secs.

Introduction

Over a decade, the demand for development of fast dissolving tablet (FDTs) has enormously increased as it has significant impact on the patient compliance. Fast dissolving tablet offer an advantage for populations who have difficulty in swallowing. It has been reported that dysphagia is common among all age groups and more specific with pediatric, geriatric population along with institutionalized patients and patients with nausea, vomiting, and motion sickness complications[1]. Fast dissolving tablet with good taste and flavor increase the acceptability of bitter drugs by various groups of population. Fast dissolving tablet are also called as fast dissolving tablet, quick disintegrating tablets, mouth dissolving tablets, fast disintegrating tablets, rapid dissolving tablets, porous tablets, and rapimelts. However, of all the above terms, United States pharmacopoeia (USP) approved these dosage forms as orally disintegrating tablets. Recently, European Pharmacopoeia has used the term fast dissolving tablet for tablets that disperses readily and within 3 min in mouth before swallowing [2, 3]. United States Food and Drug Administration (FDA) defined orally disintegrating tablet as “A solid dosage form containing medicinal substance or active ingredient which disintegrates rapidly usually within a matter of seconds when placed upon the tongue.” The disintegration time for orally disintegrating tablets generally ranges from several seconds to about a minute [4, 5].
Evaluation of tablets
Hardness - Hardness or tablet crushing strength, the force required to break a tablet in a diametric compression, was measured using Pfizer Tablet Hardness Tester [6-8]
Friability test - Friability of tablets was determined using Roche Friabilator. This device subjects the tablets to the combined effect of abrasion and shock in a plastic chamber revolving at 25 rpm   and dropping the tablets at a height of 6 inches at each revolution. Pre-weighed sample of tablets was placed in a friabilator and the tablets were subjected to 100 revolutions. Tablets were then dusted using a soft muslin cloth and reweighed [9-10]
Friability (F) = (1- Wo / W) x 10
Where,
Wo = weight of the tablets before the test.      
W = weight of the tablet after the test.
* Water absorption capacity - Water absorption ratio was determined by the following ratio0.
R = 100 x Wb / Wa
Where,
Wb = Weight of tablet before water absorption          
W =Weight of tablet after water absorption
* Wetting time - A piece of tissue paper folded twice was placed in a small Petri dish containing 6 ml of water. A tablet was put on the paper and the time required for complete wetting was measured[11, 12].
* In vitro disintegration time - Tablets were added to 10 ml of Sorenson’s buffer solution of pH 6.28 at 37 ± 0.5°C. Time required for disintegration of the tablets was noted[13].
* In vitro dissolution studies - Dissolution studies were carried out by USP-II dissolution apparatus. The tablet was taken  from each formulation to carry out the  dissolution study in the pH 6.2 buffer solution as dissolution medium (pH of saliva)[14, 15].
* Mouth feel: Mouth-feel is critical, and patients should receive a product that feels pleasant. One tablet from each batch was tested for the sensation by placing the tablet on the tongue. The healthy human volunteers were used for evaluation of mouth feel. Taste evaluation was done by a panel of 5 members using time intensity method. Sample equivalent to 40 mg i.e. dose of drug was held in mouth for 10 secs. Taste were recorded instantly and then after 10 secs, 1, 2, 4 and 6 minutes. Volunteer’s opinion for the taste were rated by giving different score values i.e. 0 = good, 1 = tasteless, 2 = slightly bitter, 3 = bitter, 4 = awful.

Materials and Methods

Gliclazide was procured by Modern Lab., Indore (M.P.), Croscarmellose sodium, Crospovidone, Sodium starch glycolate, Microcrystalline cellulose are gifted by Signet chemical corporation, Mumbai, Magnesium stearate, Aerosil was procured by Noble enterprises, Berhampur (Odisha).
FORMULATION OF FAST DISSOLVING TABLETS OF GLICLAZIDE
According to the formula given in Table 1 and 3 a total number of ten formulations were prepared by direct compression method. All the ingredients were passed through 60-mesh sieve separately and collected, finally compressed into tablets after lubrication with magnesium stearate and aerosil by using 8 mm capilet punch using RIMEK 8 station tablet compression machine. A combination of two superdisintegrants viz. crospovidone – croscarmellose, crospovidone – sodium starch glycolate were taken in 10% concentration in different ratios like 10:90, 25:75, 50:50, 75:25, 90:10 respectively. (Table 1,2,3,4)
The formulation C5 and C8 were selected based on the hardness, disintegration time and wetting time parameters. These formulations were subjected to in-vitro drug release studies. (Table 5,6,7,8,9)(Figures 1,2,3).

Results and Discussion

In the presence of disintegrants the matrix might be distorted resulting in higher surface area, allowing the super disintegrant to readily pickup water & thereby rendering rapid rate of dissolution. The concentration of superdisintegrants in the formulation also affects the dissolution rate.
The drug Gliclazide was exposed to a combination of superdisintegrants as crospovidone – croscarmellose and crospovidone – sodium starch glycolate in 10% concentration in different ratios of 10:90, 25:75, 50:50, 75:75 and 90:10 respectively. In case of CPV + CCM (10%) – 50:50 ratio was selected which showed 54.3 secs D.T and 5.0 kg/cm² Hardness, for CPV + SSG (10%) – 90:10 ratios was selected with 24.7 secs D.T and 6.3 kg/cm² Hardness. Selected formulations were exposed to t - test taking disintegration time into consideration. It was found that there is extremely significant difference in disintegration time among the two formulations. In-vitro dissolution of was carried out in phosphate buffer pH – 6.8. Formulation C5 containing CPV+SSG (10%) in 50:50 ratio showed maximum drug release of 95.06% in 30 mins compared to formulation C8 containing CPV+CCM (10%) in 90:10 ratio which showed a drug release of 92.16 %. Plots of log % drug remained Vs time were found to be linear. Dissolution data of the above formulations was exposed to drug release kinetics study. From the drug release kinetic study it is found that the formulations exhibits first order release.

Conclusion

All the formulations fulfilled the official requirements of hardness, disintegration time, wetting time and water absorption ratio. The formulation C5 was finally selected to be the best formulation among all the other formulations.

References

1. York, P., Drug Dev Ind Pharm, 1992, 18(6), 677-721.
2. Block, L.H., Pharmacopoeial forum, 2009, 35(4), 10268.
3. Avachat, A., Ahire, V.J., Indian J Pharm Sci, 2007, 69(1), 85-90.
4. Reimerdes, D., Manuf chem, 1993, 64, 14-15.
5. Jacob, S., Shirwaikar, A. A., Joseph, A., Srinivasan, K.K., Indian J Pharm Sci, 2007, 69 (5), 633-9.
6. Gohel, M.C., AAPS Pharm Sci Tech, 2007, 8(1), E1-E7.
7. Seager, H., J. Pharm and Pharmacol, 1998, 50, 375-382.
8. Dobetti, L., Pharmtech, 2001, 37, 44-48.
9. Habib, W., Khankari, R., Hontz, J., Crit Rev Ther Drug Carrier Syst, 2000, 17, 61-72.
10. Chakraborty, S., Khandi, M., Singh, S.P., Patra, N.C., Int. Journal of Green Pharmcy, 2008, 22-25.
11. Mallikarjun, S. C., Prasad, D. V. K., Gupta, V. R. M., Indian Journal of Pharmaceutical Sciences, 2008,180-185.
12. Jinichi, F., Etsuo, Y., Yasuo, Y., Katsuhide, T., Int. J Pharm, 2006, 3(10), 101-109.
13. Sharma, S., Gupta, G.D., Asian J Pharma, 2008, 2(1), 70-72.
14. Jha, S.K., Vijayalakshmi, P., Karki, R., Goli, D., Asian Jour. of Pharma, 2008, 2(4), 255-260.
15. Kuchekar, B.S., Badhan , A.C., Mahajan, H.S., Indian Drugs, 2004, 41(10), 592-598.

Source(s) of Funding

none

Competing Interests

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