Formulation and Evaluation of Fast Dissolving Tablet of Ondansetron by Utilizing Liquisolid Compact Technique

 

Sanket Jain1*, Sujit Pillai1, Rampal Singh Mandloi2, Nikhlesh Birla3

1Principal, GRY Institute of Pharmacy, Borawan, Distt. Khargone, 451228, MP., India.

2GRY Institute of Pharmacy, Borawan, Distt. Khargone, 451228, MP., India.

3GRY Institute of Pharmacy, Borawan, Distt. Khargone, 451228, MP., India.

*Corresponding Author E-mail: sanketj0960@gmail.com

 

ABSTRACT:

Ondansetron is an anti-emetic drug which is insoluble in water. The present study was aimed to formulate and evaluate oral fast dissolving tablet of Ondansetron by Utilizing Liquisolid Compact Technique. The tablets were prepared by direct compression method and characterized by UV, FTIR studies. Six formulations (F1-F6) of ondansetron were prepared and tablets were evaluated for weight variations, hardness, thickness, friability, disintegration time, drug content and In-vitro dissolution studies gave satisfactory result. TF6 was found to be the best and acceptable formulation whose drug content was about 99.17±0.05 and percentage (%) drug release 97.49±2.03 in 10 min, high as compare to other formulation and has low disintegration time 17±0.01 as compare to other formulation which indicates that drug is rapidly dissolved and available at the site of action.

 

KEYWORDS: Ondansetron, Propylene glycol, Avicel102, Aerosil200, Sodium starch glycolate.

 

 


1.0 INTRODUCTION:

The oral solid dosage form must ensure dis­solution in order to absorb from the gastro­intestinal tract. The poor dissolution rates and inadequate absorption characteristics of water-insoluble drugs are major prob­lems faced by the pharmaceutical industry.1 Dissolution properties of water insoluble drug and its release from a dosage form have a basic impact on the bioavailability.2 The oral Route is the most chosen route of drug administration because of high patient compliance and drug development. Oral bioavailability and ultimately the therapeutic efficacy of drug are determined by the extent of drug solubility and permeability. Therefore solubility is the important factor to attain desired concentration of drug in systemic circulation for pharmacological response to be shown.3,4,5

 

Various techniques have been employed to enhance the dissolution profile of water insoluble drugs such as amorphisation of drug, particle size reduction by micronisation, cogrinding, inclusion complexation, solid dispersion, self emulsifying drug delivery system, nanosuspension, hot melt extrusion.1

 

The new technique developed by Spireas ‘liquisolid system’ is the most promising method for improving the dissolution properties of poorly soluble drugs6. A liquisolid system (LS) refers to formulations formed by conversion of liquid drugs, drug suspensions or drug solution in non-volatile solvents into dry, non-adherent, free- flowing and compressible powder mixtures by blending with selected carriers and coating materials7. Drug present in the liquid medicament in LS is in the solubilized or molecularly dispersed state, so the dissolution can be enhanced by increased surface area and better wetting properties8.

 

The technique of liquisolid compact has been success­fully employed to improve the in vitro release of poorly soluble drugs like indomethacin, piroxicam, griseofulvin, ezetimibe, repaglinide, prednisolone, etc. The liquisolid technology for release enhancement has been successfully applied to low dose poorly soluble drugs1. The advantages of Liquisolid techniques include simplicity, low cost and capability of industrial production2.

 

Ondansetron is an anti-emetic drug which is insoluble in water; hence the drug may be slowly or incompletely dissolves in the gastro-intestinal tract. Ondansetron has a high oral bioavailability of 60%. The half-life is 7 h and the Tmax is 1.5 h for the conventional tablet and slightly longer for the oral drug therapy (ODT). In cancer chemotherapy, drug induced nausea and vomiting may occur so regularly that anticipatory vomiting occurs when patients return for treatment before the chemotherapeutic agent is given.9 It is used as a selective blocking agent of the serotonin 5-HT3 receptor type and also used for prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, radiotherapy or anesthesia and surgery.It is sparingly soluble in water and methanol.10

 

2.0. MATERIAL:

Ondansetron and Avicel 102 was gifted by Yarrow Chem. Mumbai, Propylene glycol and Sodium starch glycolate was gifted by Loba chemie Pvt. Ltd., Mumbai and Aerosil 200 was obtained by National Chemical, Vadodara.

 

3.0. METHODOLOGY:

3.1 Preparation of Liquisolid compacts:11

·       Ondansetron was initially dissolved in the non volatile solvent, PG as liquid vehicles to produce a drug solution.

·       Then carrier material Avicel 102 is added to the drug solution by continuous mixing in a mortar pistel.

·       To the above blend add calculated amount of coating material (Aerosil 200).

·       Before compressions of the mixture add require amount of disintegrants like sodium starch glycolate and mix it well.

·       The final mixture is passed through sieve.

·       The granules obtained are dried in tray drier at 60ºC for one hour.

·       The resultant dried granules are compressed by Tablet press.

 

3.2 Composition of Fast dissolving tablet of Ondansetron:

Table 1: Composition of Fast dissolving Tablet of Ondansetron

Ingredients

F1

F2

F3

F4

F5

F6

Drug+Liquid

40

40

40

40

40

40

R# (Carrier: Coating)

1

2

3

4

5

6

SLf  

(Loading Factor)

1.6

0.8

0.53

0.4

0.32

0.26

Avicel 102

(Carrier)

25

50

75

100

125

150

Aerosil 200 (Coating)

25

25

25

25

25

25

SSG

(Super disintegrant) 1%

0.90

1.15

1.40

1.65

1.90

2.16

Total Wt. of Tablet (mg)

91.35

116.

72

142.

1

167.

47

192.

85

218.

23

Bulk density (ρ) = (Weight of the powder /bulk volume)

 

3.3 Precompression study of Liquisolid preparation:

3.3.1 Angle of repose:

Angle of repose can be measured by fixed funnel method. The frictional forces in loose powder or granules are measured by the angle of repose. This is the maximum angle possible between the surface of a pile of powder or granules and the horizontal plane. Thus, r being the radius of the base of the conical pile.

 

tan θ = /r

 

The powder was allowed to flow through the funnel fixed to a stand at definite height. The angle of repose was then calculated by measuring the height and radius of the heap of granules formed.11,12

 

3.3.2 Bulk density:

Bulk density refers to the measure used to describe a packing of particles or granules. Bulk density is defined as the mass of powder divided by the bulk volume and is expressed in gram per milliliter (g/ml) although the international unit is kilogram per cubic meter (1g/ml=1000kg/m3) because the measurements are made using cylinders. It may also be expressed in gram per cubic centimeter (g/cm3). An accurately weighed quantity of powder, which was previously passed through sieve # 22 and carefully poured into measuring cylinder. Then after pouring the powder into the measuring cylinder, the powder bed was made uniform without disturbing. Then the volume was measured directly from the graduation marks on the cylinder as ml. The volume measured was called as the bulk volume and the bulk density is calculated by following formula.11,12

 

3.3.3 Tapped Density:

Tapped density can be defined as mass of blend in the measuring cylinder divided by its tapped volume. A given quantity of powder is transferred to a measuring cylinder (100ml) and is tapped mechanically until a constant volume is obtained. This volume is the bulk volume and it includes the true volume of powder and void space among the powder particles. The tapped density is calculated by the following formula.11,12

                           Weight of the powder

Tapped Density =--------------------------

                                 Tapped volume

 

3.3.4 Carr’s index:

The compressibility index {carr’s index} is a measure of the propensity of a powder to be compressed. It is determined from the bulk and tapped densities and is calculated using the following formulas.11

 

Carr’s index =ρt –ρb/ρt*100

Where, ρb = bulk density

 

3.3.5 Hausner’s ratio:

A flow property of powder mixture can be determined by hausner’s ratio. It is calculated by following formula and is shown in table no.5

 

Hausner’s ratio = tapped density/bulk density

A hausner ratio greater than 1.25 is considered of poor flow ability.11

 

3.3.6 Drug content:

The accurately weighed amount of each preparation containing 8mg of Ondansetron was dissolved in 100ml of phosphate buffer 6.8pH. The solution was passed through a filter paper and analyzed spectro photometrically at 248nm using UV-visible spectrophotometer after sufficient dilution with phosphate buffer pH of 6.8.11

 

3.3.7 In-vitro drug release studies:

The release rate of Ondansetron from liquisolid compact (equivalent to 8mg of Ondansetron) can be determined using USPXXII tablet dissolution testing apparatus at the basket rotation speed 50rpm. The dissolution test performed using 900ml of 6.8 Phosphate Buffer solutions at 37±0.5ºC. An aliquot sample (5ml) was withdrawn at an interval of 2min. with replacement of fresh medium and each drug solution was analyzed for Ondansetron content by spectrophotometer at 248nm.

 

Table 2: Dissolution Parametres

S. No.

Parameters

Specifications

1.

USP dissolution apparatus

Type II [Paddle method]

2.

Volume of dissolution medium

900 ml

3.

Speed of rotation

50 rpm

4.

Temperature

37º±0.5ºC

5.

Dissolution medium

Phosphate buffer pH 6.8

6.

Sample withdraw at each time interval

5ml

 

3.4 Formulation of Fast dissolving tablet by direct compression method:

Fast dissolving tablet of Ondansetron were prepared by direct compression method. The powder mixture (liquisolid compact) was mix with adequate quantity of super disintegrant and passes with sieve # 22. The compact was compressed into multi punch machine.

 

3.5 Post Compression Evaluations:13

3.5.1 Thickness:

The thickness of twenty tablets was measured by Vernier Caliper. It is expressed in mm.

 

3.5.2 Hardness:

Monsanto hardness tester can be used for the determination of the hardness. The tablet to be tested was held between a fixed and moving jaw and reading of the indicator adjusted to zero. The force applied to the edge of the tablet is gradually increased by moving the screw knob forward until the tablet breaks. Reading is noted down and is expressed in kg/cm2.

 

3.5.3 Weight variation:

20 tablet are selected randomly from the lot and weighed individually to check for weight variation. Pharmacopoeial limits are shown in table no.6

 

3.5.4 Friability:

The friability of the tablet can be determined using roche friabilator. It is expressed percentage (%). 10 tablets were initially weighed (Winitial) and transferred into the friabilator. The friabilator was operated at 25 rpm for 4 min. the tablets were weighed again (Wfinal). And the % friability was calculated as.

 

       Winitial - WFinal

F =------------------------ X 100

                 Winitial

 

3.5.5 Disintegration test:

The test was carried out on 6 tablets using tablet disintegration tester and 6.8pH phosphate buffer at 37°C ± 2°C was used as a disintegration media and the time in seconds taken for complete disintegration of the tablet with no palatable mass remaining in the apparatus was measured.

 

3.5.6 Uniformity of drug content:

The drug content can be determined by triturating 20 tablets and powder equivalent to 100 mg was added in 100ml of 6.8pH Phosphate buffer solution. Followed by stirring for 30min. and solution was filtered. The filtered solution was dilute 6.8pH Phosphate Buffer and the absorbance of resultant solution was measured spectrophotometrically at 248nm.

 

3.5.7 In-vitro drug release studies:

The release rate of Ondansetron from tablets (equivalent to 8mg of Ondansetron) can be determined using USPXXII tablet dissolution testing apparatus at the basket rotation speed 50 rpm. The dissolution test performed using 900ml of 6.8 Phosphate Buffer solutions at 37±0.5ºc. An aliquot sample (5 ml) was withdrawn at an interval of 2min. with replacement of fresh medium and each drug solution was analyzed for Ondansetron content by spectrophotometer at 248 nm.

 

4.0 RESULT AND DISCUSSION OF LIQUISOLID COMPACT:

4.0.1 Precompression evaluation of Liquisolid compact:

The Liquisolid compact of different ratio were evaluated for powder blend properties like bulk density, Tapped density, Carr’s index, Hausner ratio, Angle of repose. Results obtained are given in table 3.


 

Table 3: Precompression evaluation of Liquisolid compact

Formulation/ Parameter

Bulk density (g/ml)

Tapped density(g/ml)

Carr’s index (%)

Hausner’s ratio

Angle of repose(θ)

LSCF1

0.41±0.02

0.485±0.12

15.46±0.01

1.18±0.02

32.99±0.02

LSCF 2

0.39±0.12

0.457±0.09

14.66±0.09

1.17±0.05

31.42±0.12

LSCF 3

0.38±0.06

0.437±0.05

13.04±0.04

1.15±0.03

30.21±0.04

LSCF4

0.37±0.13

0.421±0.02

12.11±0.05

1.13±0.09

29.96±0.09

LSCF5

0.34±0.01

0.413±1.02

10.41±0.07

1.11±0.08

27.24±0.07

LSCF6

0.36±0.08

0.401±0.06

10.22±0.12

1.11±0.07

25.56±0.02

Mean, ±S.D. n=3

 


The powder mixtures for all six formulations of liquisolid compact were evaluated for bulk density which ranged from 0.41 to 0.36 (gm/cm3), tapped density ranged from 0.485 to 0.401 (gm/cm3), Carr’s index ranged from 15.46 to 10.22 %, Hausner’s ratio was found in the ranged of 1.18 to 1.11 (gm/cm3) and angle of repose ranged from 32.99º to 25.56º. All these results indicated that, the powder blend showed good flow properties into the die cavity and compressibility properties and complies with the acceptable limits.

 

4.0.2 Drug content:

The drug content range between 99.02% - 95.16% (Table: 4). The results indicate that the processes employed to prepare liquisolid compact in this study were capable of producing formulation with uniform drug content.

 

Table 4: Drug content of Liquisolid Compacts

Compact Formulation

Drugs content%

F1

95.16±0.02

F2

95.91±0.05

F3

96.74±0.01

F4

98.51±0.09

F5

99.02±0.07

F6

99.86±0.02

Mean, ±S.D. n=3

 

4.0.3 In vitro Dissolution study of Liquisolid compact:

The Dissolution rate of Ondansetron pure drug and Liquisolid compact were evaluated according to the IP Monograph of Ondansetron tablet. In comparison to the Powdered drug, product of liquisolid compact generally showed a significant increase in dissolution rate by adding of nonvolatile solvent (Table 5)


Table 5: Cumulative % Drug release of Liquisolid compact

%CDR/Time

LSCF1

LSCF2

LSCF3

LSCF4

LSCF5

LSCF6

0

0

0

0

0

0

0

2

50.95±0.02

54.43±0.09

57.09±0.02

59.28±0.09

62.43±0.05

65.07±0.05

4

64.19±0.03

67.26±0.04

70.92±0.05

74.47±0.04

77.01±0.06

80.09±0.09

6

77.28±0.05

80.19±0.01

83.51±1.02

85.78±1.04

88.02±1.02

90.89±1.02

8

83.27±0.07

85.89±1.05

88.59±1.08

90.71±0.09

92.69±1.09

95.19±0.08

10

87.29±1.02

90.49±1.07

92.33±0.01

93.99±1.04

96.43±0.04

98.89±1.04

Mean, ±S.D. n=3

 


 

Fig. 1: Cumulative % drug release of Liquisolid Compact

 

4.2 RESULT AND DISCUSSION Of TABLET:

4.2.1 Evaluation of fast dissolving tablets:

All tablets passed weight variation test as the percentage weight variation was within the pharmacopoeia limits of 7.5%. The thickness was found to be to 4.12±0.02 to 6..10±0.02mm, and the hardness of tablets was found to be 3.4±0.02 to 3.1±0.06kg/cm2 which is the required hardness for fast dissolving tablets. Thus, uniformity of hardness was observed. All the tablets showed % friability in the range of 0.45±0.02 to 0.39±0.05% which was within the limit. All the batches compiled with Pharmacopoeia and other acceptable standards required for weight variation, thickness, hardness and friability and possess sufficient mechanical strength. The disintegration time was determined by disintegration apparatus and was found to be within the range of 25 to 17 sec. which is the expected range for fast dissolving tablets. The % Drug contents of tablets from each batch were determined by UV Spectrophotometric method at wavelength 248 nm. The results showed drug content in the range of 95.27% to 99.17% which was within the acceptable Pharmacopoeia limits. The results indicated that all formulations the drug content was uniform. All these results were tabulated in table no. 6

 

4.2.2 In vitro dissolution studies of tablet:

All the six formulations were subjected for the in vitro dissolution studies using USP single station dissolution apparatus. The samples were taken at 2 min intervals and analyzed at 248nm. (Figure No. 2) shows the in-vitro release of Ondansetron fast dissolving tablet of formulation F1 to F6 from the in-vitro dissolution data show in the Table No. 19. It is clear that formulation TF1 TF2 TF3 TF4 and TF5 low solubility and drug release rate as compared to TF6. The formulation F6 showed optimum drug release profile (Figure No. 2) at predetermined rate in 10 min for all the other formulation TF1, TF2, TF3, TF4 and TF5.

 

Fig. 2: Cumulative % drug release of tablet formulations


 

Table 6: Evaluation result of Tablet

Formulation/ Parameter

Weight variation

(%)

Hardness

(kg/cm2)

Thickness

(mm)

Friability

(%)

Disintegration time

(sec)

Drug content

(%)

TF 1

Pass

3.4±0.02

4.12±0.02

0.45±0.02

25±0.05

95.27±0.02

TF 2

Pass

3.5±0.03

4.14±0.02

0.43±0.04

22±0.07

96.50±0.07

TF 3

Pass

3.4±0.08

5.13±0.02

0.44±0.01

21±0.04

97.03±0.08

TF 4

Pass

3.3±0.05

5.16±0.02

0.41±0.05

19±0.03

97.41±0.09

TF 5

Pass

3.2±0.09

6.15±0.02

0.40±0.02

19±0.08

98.73±0.06

TF 6

Pass

3.1±0.06

6.10±0.02

0.39±0.05

17±0.01

99.17±0.05

Mean, ±S.D. n=3

 

Table 7: Cumulative % drug release of Tablet Formulation’s

%CDR/Time

LSCF1

LSCF2

LSCF3

LSCF4

LSCF5

LSCF6

0

0

0

0

0

0

0

2

38.19±1.12

41.4±1.23

44.08±0.05

48.02±0.23

51.73±1.23

55.67±2.03

4

52.03±0.13

54.49±0.23

57.01±2.01

59.98±2.06

62.79±0.06

65.37±1.09

6

68.88±2.23

70.82±0.05

73.51±1.04

75.9±1.05

77.97±2.03

80.84±0.12

8

78.41±0.03

82.08±2.05

85.98±0.06

87.07±0.23

89.54±0.07

91.82±0.06

10

88.4±1.05

90.61±0.07

92.74±1.02

93.48±2.23

95.58±0.09

97.49±2.03

(Mean ± S.D., n=3)

 


4.3 Invitro dissolution of marketed tablet:

Table 8: Cumulative % drug release of Marketed Formulation

% CDR / Time

Marketed

F6

0

0

0

2

57.23

55.67

4

68.29

65.37

6

79.22

72.84

8

93.08

90.82

10

99.07

97.49

Mean, ±S.D. n=3

 

Fig 3: Cumulative % Drug release of Marketed Tablet

 

5.0 CONCLUSION:

An attempt was made to develop the Liquisolid compacts of Ondansetron to achieve fast dissolving effect and to enhance the solubility. In the present work Liquisolid tablets were prepared to improve the dissolution profile of the poorly water soluble drug, Ondansetron. Changes the properties of Ondansetron particles by simply dispersed the drug particles in a non volatile solvent, which in turn increase the wetting properties and surface area of drug particles, and hence improve the dissolution profiles of the drug. In the present work Ondansetron Fast dissolving tablets were prepared by Liquisolid compact method using Propylene glycol as a non volatile solvent, Avicel102 as carrier material, Aerosil200 as coating material and SSG as a super disintegrant. The prepared Liquisolid compacts and fast dissolving tablet formulations of Ondansetron batch have comparably good characteristics on different evaluation parameters studies; TF1 to TF6 was evaluated for drug release for 10min. with specific condition and medium. All the formulations release around 88% - 95% of drug in 10min. from the tablet formulation. But TF6 release 97% of drug in 10 min, it indicates that drug is rapidly dissolved and available at the site of action.

 

From the above study the overall rank order given for the various formulations when compared to marketed formulation. TF1<TF2<TF3<TF4<TF5<TF6<marketed. In conclusion it can be stated that the objective of the study was achieved in improving the solubility and dissolution rate of the Ondansetron using Liquisolid technology.

 

6.0 REFERENCE:

1.    Remeth Jacky Dias, Mali Krishnat Kailas, Ghorpade Sampatrao Vishwajeet, Havaldar Daulatrao Vijay, Mohite V.R. Formulation and Evaluation of Carbamazepine Liquisolid Compacts Using Novel Carriers. Indian Journal of Pharmaceutical Education and Research. 2017; Vol 51 Issue 2, pg no. 69-78.

2.    Sharma Govil, Khatry Sadhna, Arora Sandeep. Formulation and characterization of liquisolid compacts of valsartan. Journal of Pharmacy Research. 2012, 5(8), 4158-4162

3.    Yellela SRK. Pharmaceutical technologies: for enhancing oral bioavailability of poorly soluble drugs. Journal of Bioequivalence and Bioavailability. 2010; 2 no.2: 28–36.

4.    Sharma D, Soni M, Kumar S, Gupta G. Solubility enhancement: eminent role in poorly soluble drugs. Research J Pharm and Tech. 2009; 2 no. 2:220–224.

5.    Vemula VR, Lagishetty V, Lingala S. Solubility enhancement techniques. International Journal of Pharmaceutical Sciences Review and Research. 2010; 5 no. 1: 41–51.

6.    Javadzadeh Y., Nokhodchi A et. al. Liquisolid technique for dissolution rate enhancement of a high dose water-insoluble drug (carbamazepine). International Journal of Pharmaceutics, 341: (2007) 26–34.

7. Gubbi Sanjeev, Jarag Ravindra. Liquisolid Technique for enhancement of dissolution properties of Bromhexine Hydrochloride. Research J. Pharm. and Tech., 2 (2): April.-June. (2009), 382-386.

8.    Karmarkar Amrit B., Gonjari Indrajeet D et. al. Dissolution rate enhancement of Fenofibrate using Liquisolid Tablet Technique, Latin American Journal of Pharmacy, 28 (2): (2009) 219-25.

9.    Mulagada Sravanthi, Baratam Rao Srinivasa. Design and Evaluation of Ondansetron Fast Disintegrating Tablets Using Natural Polymers and Modified Starches as Super Disintegrants for the Enhancement of Dissolution. Journal of Young Pharmacists. 2017, Vol 9 Issue 4 pg no. 519-524.

10. Ramsook C, Sahagun-Carreon I, Kozinetz CA, Moro-Sutherland D: A randomized clinical trial comparing oral ondansetron with placebo in children with vomiting from acute gastroenteritis. Ann Emerg Med. 2002 Apr; 39(4): 397-403.

11. Kumari Kamala P.V., Rao Trinandar M., Rao Shrinivasa Y., M. Ashwini. Formulation and evaluation of Ketoprofen by liquisolid compact method. Int. J. Pharm. Sci. Rev.Res., 33(2), July-August 2015: Article No. 09, Pages: 45-49

12. Chandel Priya, Raj Kumari, Kapoor Ankita. Liquisolid Technique: An Approach for Enhancement of solubility: Journal of Drug Delivery and Therapeutics; 2013, 3(4), 131-137

13. L. Lachman, H. A. Lieberman, J. L. Kanig. The Theory and Practice of Industrial Pharmacy. 3rd ed. Mumbai: Varghese Publishing House: 1987, P. 297-317.

 

 

 

Received on 29.05.2021         Modified on 21.06.2021

Accepted on 26.07.2021       ©A&V Publications All right reserved

Res. J. Pharmacognosy and Phytochem. 2021; 13(4):163-168.

DOI: 10.52711/0975-4385.2021.00027