Sharma Vijay et al. IRJP 2 (5) 2011 171-174

IRJP 2 (5) May 2011 Page 171-174

INTERNATIONAL RESEARCH JOURNAL OF PHARMACY ISSN 2230 – 8407 Available online http://www.irjponline.com Research Article

FORMULATION AND EVALUATION OF MOUTH DISSOLVE TABLETS OF CEFIXIME

Sharma Vijay*1, Singh Lalit1, Saxena Pratiush1, Kumar J. Ashok2 1Dept. of Pharmaceutical Technology, SRMS CET, Bareilly (U.P.), India

2Dept. of Pharmaceutics, PRIST University, Thanjavur (T.N.), India

Article Received on: 24/03/2011 Revised on:29/04/2011 Approved for publication:18/05/2011

*Vijay Sharma, Dept. of Pharmaceutical Technology, SRMS CET, Bareilly (U.P.), India Email: vijaysrampur@gmail.com ABSTRACT Aim of this research work was to develop mouth dissolve tablet that disintegrates rapidly in mouth and formulate tasteless complex of drug Cefixime. Cefixime is an oral third generation cephalosporin antibiotic. It is used to treat gonorrhea, tonsillitis, and pharyngitis. The tablets were prepared using different concentration of disintegrant by direct compression method.The superdisintegrants used in this study were Sodium starch glycolate (SSG), cropovidone (CP), Cross‐carmillose sodium (CCS) and Kyron T 314. The formulated tablets were evaluated for uniformity of weight, thickness, hardness, friability, wetting time, water absorption ratio, disintegration time (DT) and dissolution study. The conventional tablets of Cefixime were prepared by using the same excipients ,without addition of Super fast tablet disintegrators and were evaluated in the similar way. From the results obtained, it can be concluded that the tablet formulation (batch FDT5) showed Disintegration time of 30±2.4 seconds in vitro. Also the hardness, friability and dissolution rate of prepared tablets (batch FDT5) were found to be acceptable according to standard limits. KEYWORDS: Mouth dissolving tablets, Cefixime trihydrate, Super Fast Tablet Disintegrators.

INTRODUCTION Among all route of administration, oral rote is most important and preferable route of administration of solid dosage forms1. Tablets are the most common solid dosage form, administered orally, but it is found many patients specially children, mentally ill patients and geriatrics are having problem in swallow the tablets and do not take medication as per prescription.2-3mouth dissolve tablets MDT are having advantage of ease of medication and rapid onset of action., MDTs are having advantage of rapid disintegration without use of water in oral cavity. When MDT is kept in mouth/ oral cavity then saliva quickly penetrates into tablet pores and causes rapid disintegration. A number of super fast tablet disintegrants such as croscarmellose sodium, crospovidone, sodium starch glycolate and polacrilin potassium are used for rapid disintegration. 3The formulated tablets will be characterized for various parameters like hardness, friability, disintegration, wetting and in vitro dissolution. MATERIALS AND METHODS Cefixime and lactic acid bacillus was gifted from Geneka Healthcare (Hardwar, India). Croscarmellose sodium, crospovidone, sodium starch glycolate, Polacrilin potassium, magnesium stearate and talc were purchased from S.D. Fine Chemicals Mumbai. All other solvents, chemicals and reagents were used of analytical grade.

PREPARATION OF MOUTH DISSOLVING TABLETS All the materials were passed through 60 # screens prior to mixing. Cefixime, croscarmellose sodium (CCS), mannitol, aspartame, aerosil, talc mag. stearate and lactic acid were mixed using a glass mortar and pestle. All the materials were directly compressible so this uniformly mixed blend was compressed into tablets using concave face round tooling on a rotary tablet machine. Respective batches are formulated by taking different super fast tablet disintegrants. The composition of the batches is shown in Table 1. TABLET FRIABILITY The friability of the tablets was measured in a Roche friabilator (Camp‐bell Electronics, Mumbai). Tablets of a known weight (W0) or a sample of 20 tablets are placed in a drum for a fixed time (100 revolutions) and weighed (W) again. Percentage friability was calculated from the loss in weight by using following equation. The weight loss should not be more than 1 %4. W0 ‐W

% Friability = × 100 W0 WETTING TIME The wetting time of the tablets can be measured using a simple procedure. Five circular tissue papers of

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10 cm diameter are placed in a Petridish with a 10 cm diameter. Ten millimeters of water‐ containing Eosin, a water‐soluble dye, is added to petridish. A tablet is carefully placed on the surface of the tissue paper. The time required for water to reach upper surface of the tablet is noted as a wetting time. 5 WATER ABSORPTION RATIO A piece of tissue paper folded twice was placed in a small petridish (Internal Diameter = 6.5 cm) containing 6 ml of water. A tablet was placed on the paper and the time required for complete wetting was then measured. The water absorption ratio (R) was determined using the following Equation. W a ― W b Water absorption ratio (R) = × 100 W b Where, W b is the weight of the tablet before water absorption and Wa is the weight of the tablet after water absorption. 6 IN VITRO DISINTEGRATION TEST The test was carried out on 6 tablets using Tablet disintegration tester ED‐20 (Electrolab, Mumbai, India) distilled water at 37ºC ± 2ºC was used as a disintegration media and the time in second taken for complete disintegration of the tablet with no palable mass remaining in the apparatus was measured in seconds. 7 IN VITRO DISSOLUTION STUDY The release rate of drug from mouth dissolving tablets was determined using United State Pharmacopoeia (USP) XXIV dissolution testing apparatus II (paddle method). The dissolution test was performed using 900 ml of 0.1 N HCl (PH=1.2), at 37± 0.50C and 50 rpm. A sample (10 ml) of the solution was withdrawn from the dissolution apparatus at 1, 2, 5, 10, 15, 20, 25 and 30min. The samples were replaced with fresh dissolution medium of same quantity. The samples were filtered through a 0.45 μ membrane filter. Absorbance of these solutions was measured at 288 nm using a Shimadzu UV‐1700 UV/Vis spectrophotometer. Cumulative percentage of drug release was calculated. 8 ACCELERATED STABILITY STUDY In order to determine the change in in-vitro release profile on storage, stability study of batch F5 was carried out at 400 C in a humidity chamber having 75% RH. Sample were withdrawn after three month interval and evaluated for change in in-vitro drug release pattern, hardness and disintegration time. 8, 9, 10 RESULT AND DISCUSSION The use of Superdisintegrants for preparation of fast-dissolving tablets is highly effective and commercially feasible. These Superdisintegrants accelerate disintegration of tablets by virtue of their ability to

absorb a large amount of water when exposed to an aqueous environment. Tablets formulated by using different super fast tablet disintegrators are evaluated by weight variation, thickness, hardness, percentage friability, wetting time, water absorption ratio, disintegration time and dissolution study as shown in table no. 2. Conventional tablet was prepared without adding any super fast tablet disintegrator and a comparative study was done. Formulated mouth dissolving tablets were fond to be quickly disintegrated and released the drug earlier as compared to conventional tablet. Figure 1 shows the comparative dissolution profile of all batches including conventional tablet. Results of all the batches shown that all the formulation comply with the pharmacopeial and/or standard references. Accelerated stability studies are done as per ICH guidelines. CONCLUSION Results of all the physical and in-vitro dissolution data concluded that formulation FDT5 was the most promising formulation. Tablets formulated with crospovidone, batch formulated with 7.5% crospovidone showed comparatively low disintegration time (30±2.4sec), wetting time (29 sec) and friability (0.31 %) than the other batches. So, batch formulated with 7.5% was the best batch of MDT among all the formulated batches. REFERENCES 1. Seager H, Drug-deliver products and the zydis fast-dissolving

dosage form, J Pharm Pharmacol, 1998, 50, 375-82. 2. Fu Y, Yang S, Jeong SH, Kimura S, Park K: Orally Fast

Disintegrating Tablets Developments, Technologies, Taste‐masking and Clinical Studies. Crit Rev Ther Drug Carrier Sys 2004; 21:433‐476.

3. Seager H: Drug‐delivery products and the Zydis fast‐dissolving dosage. J Pharm Pharmacol 1998; 50(4):375‐82.

4. Lachman L, Lieberman A and Kinig JL, TheTheory and Practice of Industrial Pharmacy, 4th ed, Varghese Publishing House, Bombay, 1991,67-68.

5. Battue SK, Repay MA, Maunder S and Rio MY, Formulation and evaluation of rapidly disintegrating tablet Fenoverine tablets: Effect of superdisintegrants, Drug Dev Ind Pharm, 2007, 33, 1225–1232

6. Shirsand SB, Sarasija S, Swamy PV, Kumar N, Rampure MV: Design and Evaluation of Fast Dissolving Tablets of Clonazepam. Indian J. Pharm. Sci. 2008; 70(6):791‐795.

7. Swamy PA, Areefulla SH, Shrisand SB, Gandra S and Prashanth B, Orodispersible tablets of meloxicam using superdisintegrant blends for improved efficiency, Ind J Pharm Sci, 2007,69(6), 836-840.

8. Suresh S, Pandit V, Joshi HP. Preparation and Evaluation of Mouth Dissolving Tablets of Salbutamol Sulphate. Indian J Pharm Sci 2007; 69: 467‐9.

9. Malke S, Shidhaye S and Kadam VJ, Formulation and evaluation of oxcarbazepine fast dissolving tablets, Ind J Pharm Sc, 2007,69(2), 211-214.

10. Patel MM, Patel DM, Fast dissolving valdecoxib tablets

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containing solid dispersion of valdecoxib, Ind J Pharm Sci, 2006, 68 (2), 222-226.

Table 1: Formula for Different Batches

Formula Batch

MDT1 MDT2 MDT3 MDT4 MDT5 MDT6 MDT7 MDT8 MDT9 MDT10 MDT11 MDT12 CT

Drug 100 100 100 100 100 100 100 100 100 100 100 100 100

MCC( Avicel pH 101)

77.5 71.25 65 77.5 71.25 65 77.5 71.25 65 77.5 71.25 65 -

SSG 12.5 18.75 25 - - - - - - - - - -

Cross-povidone

- - - 12.5 18.75 25 - - - - - - -

Cross-carmellose

- - - - - - 12.5 18.75 25 - - - -

Polacrilin potassium

- - - - - - - - - 12.5 18.75 25 -

Mannitol 35 35 35 35 35 35 35 35 35 35 35 35 35

Aspartame 10 10 10 10 10 10 10 10 10 10 10 10 10

Aerosil 5 5 5 5 5 5 5 5 5 5 5 5 5

Talc 5 5 5 5 5 5 5 5 5 5 5 5 5

Mag. Stearate 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5

Flavor (mango)

2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5 2.5

Lactic acid bacilli

60 million

60 million

60 million

60 million

60 million

60 million

60 million

60 million

60 million

60 million

60 million

60 million

60 million

Table 2: Evaluation of All Formulated Batches

Batch No. Weight variation (%)

Thickness (mm)

Hardness (Kg/cm2)

Friability (%)

Wetting Time (Sec.)

Water Absorption Ratio (%)

Disintegration Time (Sec.)

MDT1 Pass 3.8 3.2±0.122 0.29 41 73.75 38±1.9 MDT2 Pass 3.9 3.5±0.132 0.30 31 81.88 33±2.3 MDT3 Pass 3.6 3.5±0.213 0.39 29 88.54 31±2.1 MDT4 Pass 3.7 2.9±0.186 0.35 33 86.51 31±1.9 MDT5 Pass 3.5 3.0±0.221 0.31 29 97.12 30±2.4 MDT6 Pass 3.6 3.1±0.022 0.37 32 95.63 36±2.1 MDT7 Pass 3.7 3.4±0.082 0.29 28 91.25 35±3.1 MDT8 Pass 3.5 3.5±0.101 0.40 25 67.77 29±2.9 MDT9 Pass 3.9 3.7±0.237 0.37 24 71.19 27±2.4 MDT10 Pass 3.5 3.5±0.303 0.28 29 76.15 32±3.1 MDT11 Pass 3.6 3.4±0.125 0.35 28 74.98 30±3.6 MDT12 Pass 3.7 3.2±0.156 0.44 27 77.15 30±2.9

CT Pass 3.6 3.1±0.211 0.38 37 76.58 39±3.6

Table 3: Stability Parameters of formulation MDT5

Parameters Controlled (2-8)oC (%) After 15 days, 60 oC After one months 40/75(oC/RH)

Drug Content (%) 100.02 99.78 99.34

In-vitro Disin. Time (Sec) 25.3 25.9 26.6

Wetting Time (Sec) 29.1 29.8 30.5

Sharma Vijay et al. IRJP 2 (5) 2011 171-174

IRJP 2 (5) May 2011 Page 171-174

Figure 1: comparative Dissolution Profile of All batches

Source of support: Nil, Conflict of interest: None Declared