INTRODUCTION:

Tablets are widely used and most accepted dosage form as it provides an advantage of increased patient compliance, ease in self administration, ease in manufacturing, handling and storage as well as instability aspects. Tablets and hard gelatin capsules, apart from difficulty in swallowing for some patients, also impose another problem of disintegration or dissolution rate dependent drug action^{1, 2}. Melt in mouth tablets provide solution for both the above mentioned problems. These tablets, when placed in mouth, disintegrate rapidly in mouth without any need of water or chewing and that too within a minute. It forms a suspension in mouth which is easy to swallow for pediatrics as well as geriatrics. This suspension, when swallowed provides quicker action in comparison with conventional tablets as it by passes the disintegration stage^{2, 3, 4}. These tablets are also claimed to enhance bioavailability over conventional tablets. Melt in mouth tablets are easy to administer in case of pediatrics, geriatrics, bedridden or mentally disabled patients in comparison to conventional tablets. There is a chance of pre-gastric absorption for some drugs which may dissolve in saliva. Apart from gastric region, buccal and pharyngeal regions are also the sites of absorption^{2, 4, 5}.

The present study was conducted with an intention to develop a melt in mouth tablet of ondansetron. Sodium carboxy methyl cellulose, chitosan, crospovidone, sodium starch glycollate and alginic acid were used as superdisintegrants. Micro crystalline cellulose (MCC) was used as diluents and disintigrant^{6, 7}.

Ondansetron is a 5 HT₃ antagonist used as antiemetic to counter vomiting induced by radiotherapy or chemotherapy in cancer. It acts on 5HT₃receptors thereby blocking the depolarizing action of 5HT. Ondansetron undergoes first pass metabolism and hence has an oral bioavailability of about 60 – 70%. It is eliminated mostly metabolites into urine and faces. Its half life is 3-5 hours and it’s duration of action is 4-12 hours^{8, 9}.

MATERIALS AND METHODS:

Materials:

Ondansetron HCl was received as a gift sample from Ronak Pharmaceuticals Pvt. Ltd., Patan. Micro crystalline cellulose (MCC), magnesium stearate, pepprmint flavour, talc, sodium carboxy methyl cellulose (sodium CMC), croscarmellose sodium, crospovidone, alginic acid and sodium starch glycollate (SSG) were purchased from Central Drug House (P) Ltd., New Delhi.

Method^{10, 2, 5}

Melt in mouth tablets of Ondansetron HCl were prepared by direct compression technique. The composition tablets are as shown in Table 1. Weighed quantities of ondansetron along with required concentrations of superdisintegrants and other excipients were weighed and mixed in geometric progression in a clean and dry mortar. The blend was then passed through sieve no 60. The powder blend was then compressed into tablets using 8 mm convex faced punches on a 10 Station Rotary Tablet Machine. These Fabricated tablets were evaluated.

Evaluation:

1. Weight variation test^{2, 10,}¹¹

20 tablets were selected at random and were individually weighed. The average weight was calculated. No tablet was found to deviate from the average weight by more than ±7.5%.

2. Hardness test^{12, 13}

The hardness of tablet was measured by Monsanto hardness tester. 5 tablets were selected at random and hardness of each tablet was determined by Monsanto hardness tester. Average value of hardness of 5 tablets was determined.

3. Friability^{2,
14, 15}

Twenty tablets were selected at random and weighed. This weight is taken as initial weight. These tablets were placed in a Roche friabilator and the equipment was rotated at 25 rpm for 4 min i.e., for 100 rotations. The tablets were then taken out, dedusted, and reweighed. The percentage friability of the tablets was calculated by following formula:

4. Content uniformity ^{12, 16, 17, 18}

The content of Ondansetron HCl was determined by the following method: 10 tablets were selected at random from each batch and content of ondansetron HCl in each tablet was determined individually. A tablet was crushed in a mortar and pestle and content was transferred to a 100 ml volumetric flask containing 0.1N HCl. The flask was sonicated for 30 min and volume was made upto the mark with 0.1N HCl. Contents of the flask were filtered. The filtrated solution was diluted appropriately and the drug content was measured spectrophotometrically at 310 nm. Above procedure was repeated for all the remaining tablets.

5. Wetting time^{2, 19,}²⁰

A piece of tissue paper was folded twice and placed in a small Petri dish containing water just sufficient for thorough wetting of tissue paper. A tablet was put on the paper and the time required for complete wetting was measured.

6. In Vitro Dispersion Time^{11, 21, 22}

In vitro dispersion time was determined using phosphate buffer pH 6.8 (simulated saliva fluid). A tablet was dropped into a measuring cylinder containing 6 ml of phosphate buffer pH 6.8. The time for the tablet to completely disintegrate was noted. Six tablets were randomly selected from each batch and in vitro dispersion time was performed.

7. Dissolution Studies^{13, 18, 21, 23}

In vitro dissolution studies were performed using type II (paddle) dissolution apparatus at 50 rpm, and 900 ml of 0.1N HCl was used as dissolution medium. Temperature was maintained at 37±0.5°C. Five ml of the dissolution medium was withdrawn at specific time intervals and was filtered. Absorption of filtered solution was measured by UV–visible spectrophotometer at 310 nm. The percent of drug released was determined using standard curve. Dissolution studies were performed for all the prepared formulations and result is displayed in table 3.

Table 1: Composition of melt in mouth tablets of Ondansetron HCl

Batch Code	Ingredients (mg)
Batch Code	Ondansetron HCl	Sodium CMC	Crospovidone	Alginic acid	Croscarmellose sodium	SSG	MCC	Mannitol	peppermint flavour	Magnesium stearate	Talc
F1	8	15	-	-	-	-	40	81	3	1.5	1.5
F2	8	-	15	-	-	-	40	81	3	1.5	1.5
F3	8	-	-	15	-	-	40	81	3	1.5	1.5
F4	8	-	-	-	15	-	40	81	3	1.5	1.5
F5	8	-	-	-	-	15	40	81	3	1.5	1.5

Table 2: Evaluation of Ondansetron HCl melt in mouth tablets:

Tests	Batch code
Tests	F1	F2	F3	F4	F5
Weight variation (mg)	Pass	Pass	Pass	Pass	Pass
Hardness (kg/cm²)	3.0	3.5	4.0	3.5	3.5
% Friability	0.78	0.64	0.39	0.51	0.42
Content uniformity (mg)	7.27 ± 0.48	7.47 ± 0.51	7.35 ± 0.39	7.69 ± 0.52	7.71 ± 0.25
Wetting time (seconds)	45	27	39	36	25
In Vitro dispersion time (seconds)	38	25	35	31	22

Table 3: In vitro dissolution studies of melt in mouth tablets of Ondansetron HCl

Time (min)	% Cumulative drug release
Time (min)	F1	F2	F3	F4	F5
2	51.38 ± 0.28	44.13 ± 0.59	41.39 ± 0.51	43.81 ± 0.31	49.23 ± 0.51
4	62.91 ± 0.35	58.99 ± 0.89	52.81 ± 0.49	61.68 ± 0.81	65.13 ± 0.43
6	73.18 ± 0.28	65.15 ± 0.37	68.32 ± 0.35	78.35 ± 0.42	71.99 ± 0.59
8	87.93 ± 0.79	69.98 ± 0.42	75.84 ± 0.82	91.55 ± 0.35	89.34 ± 0.22
10	95.11 ± 0.31	83.11 ± 0.31	88.54 ± 0.21	95.39 ± 0.12	98.12 ± 0.31
12	96.28 ± 0.56	92.99 ± 0.74	93.77 ± 0.19	-	-
14	-	-	97.38 ± 0.27	-	-

Figure 1: In vitro release profile for F1 to F5.

RESULTS:

All the formulations were prepared by direct compression technique using different disintegrating agents as shown in Table 1. Parameters like weight variation, hardness, friability, drug content, wetting time, in vitro dispersion time and in vitro dissolution studies were performed and are mentioned in Table 2. All formulations were evaluated for weight variation and results indicated that all the formulations exhibit very low weight variation and lies within the pharmacopoeial limits i.e. ± 7.5%. The hardness of the tablets from each formulation was determined and was found to be in range of 3.0 to 4.0 kg/cm². The percentage friability was less than 1% for all formulations. Content uniformity of all the formulations was found to be in the range of 7.27 ± 0.48 to 7.71 ± 0.25 indicating the compliance with the pharmacopoeial limits. In Vitro dispersion time was found to be within 22 to 38 seconds. This indicates suitability of all the formulations for melt in mouth tablets. In vitro dispersion time for all the prepared formulation was found to be least for F5 followed byF2, F4, F3 and F1 respectively. Wetting time was found to be within the range of 25 to 45 seconds. In vitro dispersion time was found to be within the range of 21 to 36 second. % Cumulative drug release for all the prepared formulations was found to be in following order: F5>F3>F1>F4>F2. % Cumulative drug release from F4 and F5 formulations were found to be in 10 minutes, from F1 and F2 formulations were found to be in 12 minutes while F3 was found to be in 14 minutes. Formulation F5 shows fast dispersion.

DISCUSSION:

Different formulations were prepared using different superdisintegrants like sodium carboxy methyl cellulose, croscarmellose sodium, crospovidone, sodium starch glycollate and alginic acid. The tablets were prepared by direct compression technique. These tablets were evaluated for hardness, friability, content uniformity, wetting time and in vitro dispersion time. Prepared tablets from all the formulation disintegrated within few seconds without the need of water. Among all the superdisintegrant used, crospovidone exhibited bestresults for disintigrantion. Effect of superdisintegrants from all the prepared formulation was found to be in following order: SSG>Crospovidone>Croscarmellose sodium>Alginic acid>Sodium CMC. The formulated tablet F2 showed fast disintegration and in vitro dissolution.

ACKNOWLEDGEMENTS:

The authors are thankful to Narendra Patel, manager of Ronak Life Care Pvt. Ltd., Patan, India, for providing us gift sample of Ondansetron HCl. Our special thanks to Mr. Rajesh Asija and Mrs. Sangeeta Asija for providing us necessary support and facilities required for this research work. The authors also wish to acknowledge with thanks to the management of Maharishi Arvind Institute of Pharmacy, Mansarovar, Jaipur, for providing the infrastructure and facilities for our research project.

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Received on 30.05.2012 Modified on 23.06.2012

Research J. Pharm. and Tech. 5(8): August 2012; Page 1089-1092