Preparation and Evaluation of Ondansetron Hydrochloride Fast Dissolving Tablets

 

R.B. Desireddy,  P. Bandhavi, K. Jhansi

Nalanda  Institute of Pharmaceutical Sciences, Kantepudi, Sattenapalli.

Narasaraopeta Institute of Pharmaceutical Sciences, Narasaraopeta

*Corresponding Author E-mail:- bandhavi0031@gmail.com

 

The objective of the present study was to formulate mouth dissolving tablets of Ondansetron hydrochloride  by using sublimation technique using camphor as subliming agent and using different concentrations of superdisintegrants like crospovidone ,sodium starch glycolate, croscarmellose sodium by direct compression method. The results showed that Ondansetron with croscarmellose sodium and camphor fulfilled all the official requirements of Fast dissolving tablets.

 

 

INTRODUCTION:

Ondansetron is chemically 1,2,3,9-tetrahydro-9-methyl-3[(2-methyl-1-imidazol-1-ly)methyl]-4H-carbozol-4-one, monohydrochloride dehydrate. Ondonsteron hydrochloride dehydrate is a white powder that is soluble in water and normal saline. The active ingredient in ondansetron hydrochloride tablets is ondansetron hydrochloride as the dihydrate. It is selective blocking agent of serotonin 5HT-3 reagent.

 

Tablet is most popular among all dosage forms existing today because of its convenience of self administration compactness and easy manufacturing. however swallowing the tablets became a problem for patients suffering from problems like tremors and dysphasia. Forease administration of pediatric ,geriatric  and  psychiatric patients. This may leads to poor patient compliance. To overcome these drawbacks fast dissolving tablets have emerged as alternative oral dosage form. These are novel types of tablets and disintegrate/dissolve/disperse in saliva within a few seconds^[1][2]. According to European pharmacopoeia, the fast dissolving tablets should disperse /disintegrate in less than three minutes. These are also called as melt in mouth tablets, rapi-melt, quick dissolving tablets, mouth dissolving tablets, orally disintegrating tablets^[3].

 

Their characteristic benefits like ,rapid  onset of action, increased bioavailability ,good stability and better patient compliance make these tablets popular as a dosage form of choice. Pregastric  absorption can result in improved bioavailability and as a result of reduced dosage ,improved clinical performance through a reduction of unwanted effects^[4][5].

 

Methodology:

Instrumentation: 

UV-Visible double beam spectrophotometer, Lab India dissolution apparatus, Fourier Transform Infra Red Spectrophotometer, pH meter.

 

Materials and reagents:

Ondansetron hydrochloride(gift sample from Rashmi Pharma, Hyderabad), Crosspovidone (Alkem Laboratories, Mumbai), Sodium starch glycolate (Alkem Laboratories , Mumbai) Crosscarmellose sodium (Alkem Laboratories, Mumbai), Mannitol (Rashmipharma, Hyderabad), Magnesium carbonate (Rashmipharma, Hyderabad), Hydrochloric acid (Qualigens Fine chemicals, Mumbai). All these materials and solvents used in this study  were of analytical grade.

 

Preparation of ondansetron hydrochloride fast dissolving tablets:

Ondansetron hydrochloride fast dissolving tablets were prepared by sublimation technique using direct compression method. According to the formula given in the table 1, all ingredients were passed through 40- mesh sieve separately and collected. The weight of the drug equivalent to 500mg Ondansetron hydrochloride was taken accurately and was mixed with the other excipients and compressed into tablets, after lubrication with magnesium stearate (0.75%), and talc (1%) by using  16 station rotary tablet compression machine equipped with 9mm flat-faced punches.

 

Evaluation of tablets:

Uniformity of weight: 

Carried out as per the procedure specified in USP twenty tablets were randomly selected and weighed individually and their average weight was calculated, Percentage deviation from the average was then calculated.

 

Hardness test:

This is also known as crushing strength. The force required to crush Ondansetron hydrochloride tablets was measured using Monsanto hardness tester for 5 tablets. The average hardness  of the tablets was determined^[6][7].

 

Friability test:

Twenty tablets were randomly selected and weighed. They were subjected to abrasion using Roche friabilator at 25 rpm/min for 5min. The % friability was calculated.

 

In vitro Disintegration test:

In-vitro disintegration time was performed by apparatus specified in USP at 50 rpm .Phosphate buffer of pH 6.8, 900ml was used as disintegration medium and the temperature was maintained at 37±2⁰C and the time in seconds taken for complete disintegration of tablet, with no palpable mass remaining in the apparatus ,was measured in seconds.

 

 

 

Calibration curve method:

The drug was prepared for different concentrations by using solvent and their absorbances were calculated and listed in the table 3.

 

In vitro dissolution studies:

In vitro dissolution study was performed by using USPII dissolution test apparatus (paddle type). Phosphate buffer of pH6.8, 900ml was used as dissolution medium which was maintained at 37±0.5⁰C. Aliquots of this solution medium (5ml) were withdrawn at specific time intervals and were filtered the amount of drug dissolved was determined by UV spectrophotometer by measuring the absorbance of the sample at 310nm.Three trails of each batch were performed and average percentage drug release with standard deviation was calculated and recorded dissolution profile was listed in table 4.

 

 

RESULTS :

Table1:Formulae for the preparation of Ondonsetron hydrochloride fast dissolving Tablets

Ingredients	OFDT1 mg	OFDT2 mg	OFDT3 Mg	OFDT4 mg	OFDT5 mg	OFDT6 mg	OFDT7 mg	OFDT8 mg	OFDT9 Mg
Ondonsetron hydrochloride	4	4	4	4	4	4	4	4	4
Sodium starch glycolate	40	60	80	-	-	-	-	-	-
Crosscarmellose Sodium	-	-	-	40	60	80	-	-	-
Crosspovidone	-	-	-	-	-	-	40	60	80
Magnesium carbonate	40	60	80	40	60	80	40	60	80
Camphor	40	40	40	40	40	40	40	40	40
Mannitol	221	181	141	221	181	141	221	181	141
Magnesium Stearate	3	3	3	3	3	3	3	3	3
Talc	2	2	2	2	2	2	2	2	2
Total weight(mg)	350	350	350	350	350	350	350	350	350

 

 

Table 2:Evaluation Parameters of Ondansetron hydrochloride fast dissolving tablets.

Formulation	Thickness (mm)	Hardness (Kg/cm2)	Friability (%)	Weight variation (%)	Disintegration time(seconds)
OFDT 1	2.8±0.01	3.4±0.01	0.43±0.07	±0.43	253
OFDT 2	2.9±0.01	3.8±0.08	0.39±0.06	±0.60	165
OFDT 3	3.0±0.02	4.3±0.33	0.48±0.06	±0.74	163
OFDT 4	2.9±0.03	4.1±0.18	0.62±0.05	±0.51	150
OFDT 5	2.8±0.01	3.4±0.37	0.48±0.07	±0.53	88
OFDT 6	3.1±0.02	3.2±0.45	0.52±0.06	±0.62	52
OFDT 7	2.8±0.03	3.7±0.33	0.47±0.04	±0.51	94
OFDT 8	3.0±0.01	3.9±0.23	0.35±0.05	±0.10	91
OFDT 9	2.8±0.02	4.1±0.12	0.49±0.07	±0.60	87

 

 

Table 3: Calibration Curve for the Estimation of Ondansetron hydrochloride in 0.1 N HCl

Concentration (µg/ml)	Absorbance
0	0
2	0.1128
4	0.2122
6	0.3097
8	0.3962
10	0.4832

 

Table:4 Dissolution profile of Ondansetron hydrochloride Fast dissolving tablets employing croscarmellose sodium as super disintegrant  prepared by sublimation technique

Time (Mins)	OFDT 6
0	0
5	88.64±0.61
10	95.40±0.15
20	100.02±0.12
30	-
45	-
60	-

 

Dissolution profile for formulation OFDT 6:

 

DISCUSSION:

The data obtained for the evaluation of tablets was given in the table 2. All the parameters done were within the official limits. Based on the disintegration time, the superdisintegrants  are ranked as croscarmellose sodium > crospovidone> sodium starch glycolate. In case of formulations OFDT 3,OFDT 6,OFDT 9 the minimum disintegration time was found to be 163,52,87 seconds respectively. The faster disintegration of the of super disintegrants can be attributed to the increase in the rate and extent of water uptake and consequent swelling and increased hydrodynamic pressure to induce complete disintegration^[8][9]. With the objective of selecting the best subliming agent, fast dissolving tablets were formulated by sublimation technique, as per the formulations in table 1.on the basis of results obtained in the preliminary screening studies, the formulation (OFDT 6) containing 20% concentration of croscarmellose sodium showed fastest disintegration. Hence it was selected for further studies.

 

CONCLUSION:

The basic method considered for the development of ondansetron hydrochloride fast dissolving tablet is the direct compression method by using mannitol as diluent and croscarmellose sodium, crospovidone, sodium starch glycolate as super disintegrating agents at different concentrations and camphor as sublimating agent .From the method by comparing different concentrations of OFDT formulations the formulation (OFDT 6) has less disintegration time and fulfilled all the official requirements of Fast dissolving  tablets.

 

REFERENCES:

1        Van Schaick EA et al; Pharmacokinetic comparison of fast disintegrating  and conventional tablet formulation of risperidone in healthy volunteer.Clin.Ther.2003;25:1687-99.

2        Virley P et al; A novel, fast dissolving dosage form; Manufacturing Chemist.(1990),36:36-37.

3        Dobetti L et al; Fast melting Tablets: Developments and Technologies. Pharm. Tech.,(2001):44-50.

4        Koizumi  K, et al; New method of preparing  high porosity rapidly saliva soluble compressed tablets using mannitol with camphor, a subliming material; Int J Pharm.(1997);152:127-131.

5        Rajyaguru T H, et al; Novel approach-fast dissolving tablets. Indian drugs.(2002),39(8):405-409.

6        Watanabe Y, et al; New compressed tablets rapidly disintegrating in saliva in the mouth using crystalline cellulose and a Disintegrant. Bio. Pharm. Bull.(1995);18:1308-1310.

7        Ishikawa T, et al; Preparation and evaluation of tablets rapidly disintegrating in saliva containing bitter taste masked granules by the compression method. Chem Pharm. Bull. (1997), 47(10): 1451-1454.

8        Nadendla R R et al; Current status of dispersible dosage forms. Int J Pharma. Excip. (2002), 2:25-28.

9        Habib W, et al; Fast dissolving drug delivery systems, critical review in therapeutics. Drug carrier Systems. (2000),17(1):61-72.

10     Chang R, et al, Fast dissolving tablets; Pharma. Tech. (2000),24(6):52-58.

11     Corveleyn S, et al. Formulation and production of rapidly disintegrating tablets by lyophilisation using hydrochlorthiazide as a model drug. Int J Pharm.(1997),152:215-225.

 

 

 

Accepted on 16.06.2013      © RJPT All right reserved