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ISSN: 2229-3787

Journal of Advanced Pharmaceutical Research. 2015, 6(1), 11-14. Research Article

Comparative Evaluation of Formulated and Marketed Products of Nimesulide Dispersible Tablets Ramya Krishna Seelam *, Eliyas Kadi Abafita Department of Pharmacy, College of Public Health and Medical Sciences, Jimma University, Jimma, Ethiopia Corresponding author: [email protected] Received: April-2015; Accepted: April-2015 ABSTRACT Dispersible Tablets are a kind of tablets designed for pediatric use. These are the tablets which rapidly disperse in water and form a smooth dispersion for oral administration to children. Nimesulide is a relatively cox-2 selective, non-steroidal anti-inflamatory drug (NSAID) with analgesic and antipyretic properties. It has a multifactorial mode of action and is characterized by a fast onset of action. Nimesulide is also a pediatric medicine at a dose of 50 mg. A few commercial dispersible tablets of Nimesulide and also Nimesulide suspensions are available in market for pediatric use. Nimesulide is a crystalline and poor bioavailable drug because of its hydrophobicity and poor aqueous solubility. The objective of the study was to prepare and evaluate Nimesulide dispersible tablets by Direct compression and Wet granulation techniques and comparing their physical parameters and dissolution data with marketed product. The formulated tablets show higher dissolution rates than the marketed product of Nimesulide.

Keywords: Nimesulide; Dispersible tablets, Direct compression, Wet granulation, Pediatric.

Introduction : Dispersible Tablets are a kind of tablets designed for pediatric use. These are the tablets which rapidly disperse in water and form a smooth dispersion for oral administration to children. Pharmacopeas (I.P and USP) prescribed the following additional requirements for dispersible tablets (Suresh, 2009). (i)The disintegration time is not more than 3 minutes. (ii)Test for uniformity of dispersion-when one or two tablets are dispersed in water, the dispersion formed should pass through mesh no: 20 without leaving any particles on the mesh. Nimesulide is a relatively cox-2 selective, nonsteroidal anti-inflamatory drug (NSAID) with analgesic and antipyretic properties. It has a multifactorial mode of action and is characterized by a fast onset of action. Nimesulide is also a pediatric medicine at a dose of 50 mg. A few commercial dispersible tablets of Nimesulide and also Nimesulide suspensions are available in market for paediatric use (Praveen, 1998).

The objective of the present experiment is to formulate and evaluate dispersible tablets of Nimesulide. Dispersible tablets if Nimesulide were formulated employing cross provide (a super disintegrant) and aerosol (a dispersant). For comparison, commercial Nimesulide tablets were also evaluated. Materials and Methods : Nimesulide is obtained as a gift sample from Dr. Reddy’s Lab, Hyderabad. Lactose, cross povidone, aerosol, talc, Magnesium stearate, PVP and all other chemicals used in the study were of analytical grade. Preparation of Dispersible Tablets Nimesulide dispersible tablets were prepared by wet granulation, D.C methods as per the formula given in table 1. Preparation of tablets by wet granulation methods 1. Nimesulide, PVP and Lactose were blended thoroughly in a dry mortar. The blend was then granulated with water; alcohol (1:1) solution as granulating fluid. The

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Available online at www.pharmresfoundation.com duff mass was pressed through mesh no: 12 to form wet granules. 2. The wet granules were dried at 60 o C for 1 hr. The dried granules were again passed through mesh no: 12 to break the aggregates. 3. Cross povidone, aerosol, Talc and Mg. stearate were passed through mesh no: 80 and mixed with tablet granules. 4. The tablet granulations were then compressed into tablets of 230 mg using 8 mm round flat punches on a CADMACH tablet punching machine.

ISSN: 2229-3787

Results and Discussion : Dispersible tablets of Nimesulide were prepared by wet granulation and direct compression methods. In the wet granulation method, PVP (1 %) as binder and water as a granulating fluid were used. In direct compression method, Lactose-starch (80: 20) directly compressible vehicle prepared in laboratory were used as vehicle. All the prepared tablets were evaluated for disintegration time, uniformity of dispersion and dissolution characteristics. The results are given in tables 2- 4 and figure 1.

Table 1: Formula of Nimesulide Dispersible Tablets Preparation of Tablets By direct compression method 1.Nimesulide, cross-povidone, aerosol were thoroughly blended in a dry mortar. The blend was transferred into a polythene bag. 2.Lactose-starch (DCV), Talc and Mg. stearate were added to the blend of drug and other materials were taken in polythene bag. 3.The mixture was blended thoroughly by shaking. 4.The blend of powder (drug and other excipients) was compressed into tablets on a CADMACH 16 station tablet compression machine.

INGREDIENTS

WET GRANNULATION

DIRECT COMPRESSION

Nimesulide

50 mg

50 mg

Lactose Cross povidone(5%)

152.4 mg

-

11.5 mg

11.5 mg

Aerosil(2%)

4.6 mg

4.6 mg

talc(2%) magnesium stearate(2%)

4.6 mg

4.6 mg

4.6 mg

4.6 mg

PVP(1%) DCV(LactoseStarch)

2.3 mg

-

-

154.7 mg

Evaluation of tablets The tablets prepared were evaluated for; (i) (ii)

Disintegration time Dissolution rate study

Disintegration time: The disintegration time of tablets were determined in a thermonik tablet disintegration test apparatus using water as a fluid. Dissolution rate study: The dissolution rate of Nimesulide tablets prepared was studied in 900 ml of phosphate buffer of pH 7.4 using Electrolab eight station dissolution rate test apparatus employing paddle stirrer at 50 rpm and temperature was maintained at 37 o ± 1 o C. For one tablet containing 50 mg of Nimesulide was used in each test. Five ml of samples of dissolution fluid were withdrawn through a filter. The volume withdrawn (5 ml) was replaced with drug free dissolution fluid. The samples were suitably diluted and assayed at 395 nm using UV spectrophotometry.

Table 2: Dissolution data of Nimesulide Dispersible tablets Time (hrs)

Wet Granulation

Direct Compression

Commercial

0

-

-

-

5

23.11

11.91

4.5

10

30.22

21.954

6.98

15

35.91

28.31

8.576

20

38.576

31.82

11.117

25

40.754

35.688

15.882

30

43.066

39.82

21.652

40

48.442

43.998

23.77

50

52.442

45.776

26.95

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Available online at www.pharmresfoundation.com Figure 1: Comparison of Nimesulide dissolution data

ISSN: 2229-3787

The formulated dispersible tablets gave rapid and higher dissolution of Nimesulide when compared to commercial formulation. Among the two methods, wet granulation method gave relatively higher dissolution than direct compression method. As nimesulide is a hydrophobic drug its particles are wetted with relative ease; in the wet granulation method by the presence of hydrophobic binder PVP resulting in a relatively higher dissolution.

Conclusion :

Table 3: Physical parameters of Nimesulide tablets Nimesulide

Wet grannulation Direct compression Commercial

Hardness (kg/cm^2)

Fraibility (%)

Disintegration time (min-sec)

5

0.5

2 min50sec

4

0.51

1min-10sec

4

0.4

45 sec

Table 4: Dissolution parameters of Nimesulide tablets Nimesulide

PD10 (%)

T50 (min)

K1 (1/min)

DE30 (%)

Wet granulation Direct compression

30.22

44 min

0.0117

31.309

21.954

55 min

0.0116

25.265

Commercial

6.988

-

0.005

8.778

Dispersible tablets formulated by direct compression method disintegrated in 1 min-10 sec, whereas these prepared by wet granulation method disintegrated in 2 min-50 sec. The commercial tablets disintegrated within 45 secs. Hence all the prepared and commercial dispersed tablets fulfill the official (I. P) disintegration time specifications of dispersed tablets. In the test for uniformity of dispersion, the dispersion formed in water was completely passed through mesh no: 20 fulfilling the official (I. P) specifications for uniformity of dispersion. These results are comparable with the findings reported in Gupta, 2007.

Nimesulide dispersible tablets could be formulated by both wet granulation and direct compression methods. Dispersible tablets prepared by both the methods as well as the commercial dispersible tablets fulfill the official (I. P) specifications regarding Disintegration time, test for uniformity of dispersion prescribed for dispersible tablets gave relatively higher dissolution rates when compared to commercial product.

Acknowledgement : The authors would like express sincere thanks to the management of Jimma University (College of Public Health and Medical Sciences) for providing the necessary facilities in carrying out this work.

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Formulation Design and Optimization of Mouth Dissolve Tablets of Nimesulide Using Vacuum Drying Technique, AAPS Pharm. Sci. Tech, 2004; 5(3):1-6. 6. Gupta Venkadari Rammohan, Mutalik Srinivas Patel Madhobhai M., Jani Girish K., Spherical crystals of celecoxib to improve solubility, dissolution rate and micromeritic properties, Acta Pharm. 57 (2007): 173– 184. 7. Axel Knoch., and Isaac Ghebre-Sellassie., Pelletization technique, Encyclopedia of pharmaceutical technology, Marcell Dekker, Inc., New York. , 2002. 8. Indian pharmacopoeia, Vol. 2, Govt. Of India, Controller of Publications, New Delhi, 1996; A- 100. 9. Zade,P.S., Kawtikwar P.S ., Sakarkar D.M. , Formulation, Evaluation and Optimization of Fast dissolving tablet containing Tizanidine Hydrochloride, Int. J. Pharm Tech Res., 2009, 1(1):34-42.

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