Central Journal of Drug Design and Research

Cite this article: Bhatt S, Sharma D, Mandge S, Sharma S, Jain V (2015) Design and Optimization of Taste Masked Fast Dissolving Tablet of Ondansetron Hcl using Full Factorial Design. J Drug Des Res 2(2): 1011.

*Corresponding authorShailendra Bhatt, Maharishi Arvind Institute of Pharmacy, Jaipur, Rajasthan, India, Tel: 08107663903; Email:

Submitted: 07 March 2015

Accepted: 02 April 2015

Published: 06 April 2015

Copyright© 2015 Bhatt et al.

OPEN ACCESS

Keywords•Optimization•Factorial design•Fast dissolving tablet•Mechanical strength•Pharmacokinetics data•Bioequivalence

Research Article

Design and Optimization of Taste Masked Fast Dissolving Tablet of Ondansetron Hcl using Full Factorial DesignShailendra Bhatt1*, Divya Sharma1, Shailendra Mandge2, Swapnil Sharma3 and Vikas Jain4

1Maharishi Arvind Institute of Pharmacy, Jaipur, India2Nektar Therapeutics (India) Pvt. Ltd., Hyderabad, India3BanasthaliVidyapith, Rajasthan, India4Mahakal Institute of Pharmaceutical Studies, Madhya Pradesh, India

Abstract

The purpose of this work was to develop taste masked fast dissolving tablets of Ondansetron HCl that overcomes principle drawback of such formulations, which is slow disintegration and inadequate mechanical strength. In the present work taste masked Ondansetron HCl fast dissolving tablets were formulated and optimized by using different ratio of MCC in MCC: Lactose combination and different concentration of Ac-Di-Sol. A 32 full factorial design and statistical models were applied to optimize the effect of two factors. It was observed that the responses, i.e., disintegration time and hardness were affected by both the factors. The statistical models were validated and can be successfully used to prepare fast dissolving tablets of Ondansetron HCl with rapid disintegration (24 seconds) and excellent mechanical strength (4.4 kg/cm2). Pharmacokinetic studies in rats showed statistically insignificant difference (p>0.05) between OFDT1 and marketed product (Ondem MD 8), concluded that optimized FDT was found to be bioequivalent in rate and extent of absorption with the marketed formulation. While, The values of Tmax were found to be 1 h and 2 h for OFDT1 and Ondem MD8, respectively, showed quick onset of action with OFDT1. Stability studies was performed on optimize tablet and it was concluded that formulations were stable and no significant change in the percentage drug content, hardness, disintegration time and drug release was to be observed.

INTRODUCTIONOndansetron HCl is a potent selective serotonin 5HT3 receptor

antagonist which has a role in prophylaxis of postoperative chemotherapy/ radiotherapy induced emesis. The adult dose is 8 mg and its metabolites are excreted in urine with about 10% of unchanged drug and having 67% of bioavailability through oral route [1]. This makes Ondansetron HCl a suitable candidate for fast dissolving dosages form.

Oral route is the preferred route for drug administration. Thus the problems like bitter taste and ease of the swallowing need to be solved. Fast dissolving tablets (FDT) are very beneficial for the patient with difficulties in swallowing and during travelling. FDT dissolve fast and exert rapid onset of action.

FDT can be formulated using different methods. A number of them engage increasing the porosity of the tablet and decreasing the disintegration time (DT) [2]. Super Disintegrants are used that swell or absorb water rapidly to disintegrate the tablet [3]. Technologies like Zydis based on lyophilization yield tablets that

dissolve in a small number of seconds. Generally the techniques try to lower the disintegration time, but compromise with the mechanical potency. A Zydis tablet requires ingular packaging and patient counselling for removing the tablets from the strip [4]. Hence, the objective of this work was to formulate and optimize fast dissolving tablets of Ondansetron HCl that disintegrate in a few seconds and possess good mechanical strength.

Hence in the present investigation, a novel approach is used to combine microcrystalline cellulose and lactose in different ratio with a super disintegrant and formulate FDT which assessing improved bioavailability. Effects of Ac-Di-Sol and different concentration of MCC in microcrystalline cellulose: lactose combination on disintegration time and hardness of the tablets were optimized using a 32 factorial design, and mathematical models were validated.

MATERIAL AND METHODS

Material

Ondansetron HCl was obtained as a gift sample from Cadila

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Pharmaceutical limited, Ahmedabad. Ondem MD 8 (Alkem laboratory Ldt) was purchased from local drug store. Aminoalkyl methacrylate copolymer (Eudragit EPO) was a gift from Evonik Industries, Germany. Cross carmellose sodium (Ac-Di-Sol), were received as a gift sample from Torrent Research Centre Ahmedabad, Micro crystalline cellulose, Lactose and magnesium stearate were purchased from S.D. Fine Chemicals, Mumbai. Sodium saccharine was purchased from Loba Chemicals Mumbai. All other chemicals used in the study were of analytical grade.

Methods

Preparation of drug polymer complex: The drug polymer complex (DPC) was prepared and characterized as per previously published method [5].

Formulation development: DPC was used to prepare FDT by direct compression technique. Composition of tablet is mentioned in (Table 1). All the raw materials were passed through a # 60 sieve prior to mixing. Drug polymer complex (1:5), containing amount equivalent to 10 mg of Ondansetron HCl, was mixed with the other excipients. The powder blend was lubricated with magnesium stearate and compressed on a 10 station mini press tablet machine (CPMD 3-10, Chamunda Pharma Machinery Pvt. Ltd., Ahmedabad, India.) equipped with 9 mm concave punch.

Experimental design of Ondansetron HCl fast dissolving tablets: A randomized 3 level full factorial design using two factors was adopted to systematically study the formulation of FDT of Ondansetron HCl. A sum of 12 trial run with 3 centre points were performed at all possible combinations (Table 2). The amount of MCC in MCC: Lactose combination (X1) and the super disintegrant (Ac-Di-Sol) concentration (X2) were selected as independent variable. The disintegration time and hardness were selected as dependent variable. The responses were analysed for analysis of variance (ANOVA) using Design Expert version8.0 software. Statistical models were generated for each response parameter. The models were tested for significance.

Validation of statistical model: Levels of equally the factors were selected at two diverse points and responses predicted by the statistical models were calculated. Fast dissolving tablets were prepared using these levels and responses were measured practically. The predicted responses were compared against observed responses and closeness between them was checked.

Response surface plots: Response surface plots were generated for each response to study the effect of both factors on each response.

Evaluation of prepared tablets

Uniformity of Mass: The test was performed as per

specification given in I.P.1996 on 20 tablets. The maximum acceptable limit is ± 5% deviation of an individual mass from average mass.

Friability: Tablet Friability was measured using Roche Friabilator according to specification given in IP 1996. This device subjects the tablets to the combined effect of abrasions and shock in a plastic chamber revolving at 25 rpm for 4 min. The tablets were dedusted, and the loss in weight caused by the fracture and abrasion was recorded as the % weight loss. Friability below 1% was considered acceptable.

Where, W0 is initial weight of the tablets before the test and W is the weight of the tablets after test.

Hardness: Hardness of the tablet of each formulation was determined using Pfizer hardness tester.

Wetting time: A piece of tissue paper folded twice was kept in a culture dish (internal diameter 5.5 cm) Containing ~6 mL of purified water. A tablet having a small amount of amaranth powder on the upper surface was placed on the tissue paper. The time required to develop a red colour on the upper surface of the tablet was recorded as the wetting time [6].

Disintegration time: Disintegration of fast dissolving tablets is achieved by saliva in the mouth, however amount of saliva in the mouth is limited and no tablet disintegration test was found in USP and IP to simulate in vivo condition. The disintegration time was measured using a modified disintegration method. According to this method, a Petri dish of 10 cm diameter was filled with 10 ml of distilled water, the tablet was carefully places at the centre of the Petri dish, and the time necessary for the complete disintegration of the tablet in to fine particles was noted as disintegration time [7].

Uniformity of drug content: The test is obligatory for tablets containing less than 10 mg or less than 10 % w/w of active ingredient. This test was performed as per Indian Pharmacopoeia, 1996. A tablet was crushed and dissolved 1 ml of dilute hydrochloric acid and 30 ml of distilled water. This solution was shaken for 15 min. the volume of this solution was made up to 50 ml with distilled water and centrifuged. Five millilitres of the clear supernatant was mixed with 10 ml of 0.1 M hydrochloric acid, and made up to 100 ml with distilled water. The absorption of the solution was determined spectrophotometrically at 249 nm. The same procedure was followed for another nine tablets.

Dissolution studies: Tablet test condition for the dissolution rate studies were used according USP specification using USP 24, type II apparatus. The dissolution medium was 900 ml of 0.1 N HCl (pH 1.2). The temperature of the dissolution medium and the rate of agitation were maintained at 37±0.50 C and 50 rpm respectively. Aliquots of 10 ml of dissolution medium were withdrawn at specific time interval and the volume replaced by fresh dissolution medium, pre warmed to 37±0.50C. The drug concentration was determined spectrophotometrically at 249 nm using UV spectrophotometer (Shimadzu S 1700, Japan).

Pharmacokinetic study: Seven-week-old male Wistar rats were used in the present experiment. The mean weight was found to be 264.66 ± 8.96 g in the range of 259-275 g. All the animal experiments were performed according to the guideline

Ingredients % (w/w)

Ac-Di-Sol 2-6

MCC 0-70

Lactose 100-30

Mag. Stearate 1.5

Saccharine sodium 0.6

Table 1: Percentage of different ingredients used in the preparation of fast dissolving tablet.

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Batches

Real value Transformed value Responses%

MCC in MCC: Lactose combination

%Ac-Di-Sol X1 X2

DisintegrationTime (sec)

Hardness(kg/cm2)

OH1 70 2 1 -1 30±0.98 4.5±0.29

OH2 50 4 0 0 30±0.52 4.1±0.17

OH3 30 4 -1 0 34±0.49 3.9±0.44

OH4 50 4 0 0 30±0.73 4.1±0.98

OH5 50 2 0 -1 35±0.31 4.2±1.0

OH6 30 2 -1 -1 30±0.78 3.8±0.29

OH7 50 4 0 0 30±0.71 4.2±0.37

OH8 70 6 1 1 22±0.82 4.7±0.59

OH9 30 6 -1 1 32±0.39 4.2±0.71

OH10 70 4 1 0 26±0.63 4.6±0.33

OH11 50 4 0 0 29±0.57 4.1±0.20

OH12 50 70 0 1 26±0.43 4.4±0.51

Table 2: Three level full factorial design layout of Ondansetron HCl Fast dissolving tablet.

X1 is transformed value of % of MCC in MCC: Lactose combination; X2 is transformed value of % of Ac-Di-Sol. * Values given as mean±standard deviation (n=3).

of local animal ethical committee (Ref no- BU/BT/185/11-12). The Test (OFDT 1) formulation and Reference (Ondem MD 8) were administered to the rats by gastric intubation method after calculating the animal dose [8]. In gastric intubation method suspension of test and reference product was prepared using small amount of water and it was administered to animal orally. Blood samples were withdrawn after 0, 0.50, 1, 2, 4 and 6 hrs. Blood specimens were taken in a centrifuge plastic capillary tube and subjected to centrifugation at 10,000 rpm for 15 min then plasma was taken in a polyethylene tube and stored at −20◦C until assay.

Analysis of plasma sample and data analysis: Quantitative determination of Ondansetron HCl was carried out by HPLC method using shimadzu HPLC system consist of consist of pump (Perkin Elmer, USA) with universal loop injector (Rheodyne) of injection capacity 20 μl, equipped with a UV-visible detector with reversed phase column used was RP-C18 brownlee (5μm particle size, 250 mm x 4.6 mmi.d.) at ambient temperature. The mobile phase consisted of Acetonitrile: Buffer (KH2PO4, pH 5.5, 0.02 M) 60:40 % v/v and flow rate was adjusted to 1ml/min [9]. The concentration of Ondansetron was determined by HPLC-UV at 220 nm. The method showed high sensitivity with good linearity (r2=0.9971) over a tested concentration range 6-60 ng/ml.

Pharmacokinetic analysis: Pharmacokinetic parameter was determined from the plasma concentration vs time data using non compartmental analysis. Statistical analysis was done using ANOVA (p>0.05).

Stability study: The results of tablet characterization of different batches were compared and optimized batch (OFDT 1) was selected for stability study. The FDT was packed in wide mouth air tight glass container. Stability studies were carried out according to ICH and WHO guidelines.

The tablets are withdrawn after end of period and analysed for physical characterization and drug content. A dissolution

profile comparison between pre-change and post-change product or with different strength, helps assure similarity in product performance and signal bioequivalence.

Among several methods investigated for dissolution profile comparison, f2 is the simplest one.

f2= 50* log {*1 + (1/n) Σt=1n (Rt - Tt)2] -0.5 * 100}

Where Rt and Tt are the cumulative percentage drug dissolved at each of the selected n time points of the reference (before storage) and test (after storage) product respectively. When the two profile are identical, f2 = 100. An average difference of 10% at all measured time point’s results in f2 value 50. FDA sets a standard of f2 value in between 50 to 100; indicate similarity between two dissolution profiles.

RESULTS AND DISCUSSION

Evaluation of tablets

The outcomes of various evaluation parameters are shown in (Table 3). The in vitro drug release profile of all factorial batches and optimized batches were more than 95% in 4 minutes than compare to 90 % in 10 minutes for marketed product (Ondem MD8) as shown in (Figure 3).

Statistical design: A statistical model incorporating interactive and polynomial terms was used to evaluate the responses.

Y= b0 + b1 X1+ b2 X2+ b12 X1 X2 + b12 X1

2 + b22 X2

2 + b12b2 X1

2 X2

Y is the measured response associated with each factor-level combination, b0 is the arithmetic mean response of the total 12 runs; X1 and X2 are the factors studied, bi is the regression coefficient for factor Xi computed from the observed response Y. The main effects (X1 and X2) represent the average result of changing one factor at a time from its low to high value. The interaction terms (X1X2) show how the response changes when

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Parameters* Thickness Weight Friability Drug Content Wetting time

Formulations (mm) (mg) (%) (%) (Seconds)

OH1 3.8±0.12 250.5±1.13 0.28±0.17 99.0±1.21 20±1.29

OH2 3.9±0.73 249.8±1.71 0.35±0.40 99.38±1.14 21±1.42

OH3 3.9±0.21 251.0±1.62 0.41±0.59 98.57±1.11 52±1.20

OH4 3.9±0.31 248.5±1.20 0.35±0.49 97.51±1.33 25±1.38

OH5 3.9±0.12 250.8±1.21 0.34±0.27 99.29±1.22 28±1.05

OH6 3.8±0.51 249.±1.32 0.42±0.38 96.92±1.41 21±1.29

OH7 3.9±0.26 250±1.28 0.31±0.47 98.49±1.71 20±1.14

OH8 3.9±0.50 251.0±1.11 0.28±0.24 97.54±1.29 15±1.44

OH9 3.9±0.30 250.0±1.24 0.31±0.40 98.29±1.31 22±1.04

OH10 3.8±0.21 249.5±1.17 0.28±0.62 99.74±1.30 18±1.29

OH11 3.8±0.20 250.0±1.07 0.36±0.55 100.5±1.42 20±1.19

OH12 3.9±0.21 250±1.28 0.29±0.63 98.5±1.19 18±1.28

Table 3: Characterization of Ondansetron HCl Fast dissolving tablet.

*Values given as mean±standard deviation (n=3).

Model* b0 b1 b2 b12 b12 b2

2 b12b2

FM 29.79 -4.33 -4.50 -0.50 0.13 0.63 1.0

RM 29.79 -4.33 -4.50 - - - -

Model* b0 b1 b2 b12 b12 b2

2 b12b2

FM 4.17 0.32 0.13 - - 0.13 -

Table 4: Summary of result of regression analysis.

*FM indicate full model; RM indicate reduced model

Response model Sum of square df Mean square F value P value R2 Adeq. precision

DT 204.54 6 34.09 151.51 <0.0001 9945 43.244

Table 5: ANOVA for Response Surface Reduced Cubic Model for disintegration time.

Figure 1 Response surface plot for DT.

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two factors are simultaneously changed. The polynomial terms (X1

2 and X22) are included to investigate nonlinearity. Two

conclusions could be drawn from the equation: (1) a coefficient with a negative sign increases the response when the factor level is decreased from a higher level to a lower level, and (2) the factor with a higher absolute value of the coefficient and a lower significance value P” has a major effect on the response variables.

The dependent variables, Disintegration time and Hardness showed a wide variation (22 s to 35 s and 3.8 to 4.7 kg/cm2 respectively). The data clearly indicates that the response variables are strongly dependent on the selected independent

variables. The high values of the correlation coefficient for disintegration time and the hardness indicate a close fit.

The fitted equations (full and reduced) relating the responses to the transformed factor are shown in (Table 4). Analysis of variance (ANOVA) was carried out to identify the insignificant factors (Table 5) and (Table 6), which were then removed from the full model to generate the reduced model.

The Model F-value of 151.51.13 and 45.14 for disintegration time and hardness implies the model is significant. There is only a 0.01% chance that a “Model F-Value” this large could occur due to noise. Value of probability >F less than 0.0500 indicate that

Response model Sum of square df Mean square F value P value R2 Adeq. precision

Hardness 0.76 3 0.25 45.14 <0.0001 9752 20.785

Table 6: ANOVA for Response Surface Reduced Quadratic Model.

Figure 2 Response surface plot for hardness.

Figure 3 In vitro release profile of optimized formulation (OFDT1) and Marketed product (Ondem MD 8).

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model term are significant. Values greater than 0.1 indicates that the model terms are not significant. Adequate precision measures the signal to noise ratio. A ratio greater than 4 is desirable; ratio of 43.244 and 20.785 indicates an adequate signal. This model can be used to navigate the design space.

For disintegration time, the coefficients of X1 and X2 that is, b1, and b2respectively, bear a negative sign, thus on increasing the concentration of MCC in MCC-Lactose combination and concentration of Ac-Di-Sol, a decrease in disintegration time is observed. For hardness, the coefficients of X1 and X2 that is, b1, and b2respectively, bear a positive sign thus on increasing the concentration of MCC in MCC-Lactose combination and concentration of Ac-Di-Sol, increase in hardness is observed.

Validation of statistical model: To validate the statistical model checkpoint batches, CP1 and CP2 were prepared according to the formula (Table 7). From the response surface plot (Figure 1) and (Figure 2), and the calculations from the statistical equation obtained by regression, the results revealed the close match of the experimental results. Thus, we can conclude that the statistical model is mathematically valid.

The best batch was selected after considering the requirements of an FDT. To full fill these requirements, Disintegration time and hardness was targeted to 25 s and 4.5 kg/cm2. The batches’ dissolution rates were also considered and batches with higher dissolution rates were given priority. Different constraints were applied and solution with desirability 1 was selected (Table 8) and (Table 9).

To determine the suitability of the powder blend for tablet compression, optimized FDT was characterized for various flow properties (Table 10). The tablet blend showed good flow ability (angle of repose < 300).

Friability of optimized tablet was below 1% which showed good mechanical resistance. All the parameters i.e. thickness, diameter, weight, drug content and wetting time were under acceptable limits (Table 11).

Comparison of predicted responses and observed values for the optimized tablet (OFDT 1) were in close agreement (Table 12), and the models were found to be valid. Thus, full factorial design with two factors can be successfully used to optimize the formulations.

Figure 4 Plasma concentration of Ondansetron HCl vs time profile of reference (Ondem MD8) and test (OFDT1).

0

20

40

60

80

100

120

0 2 4 6 8

Cum

ulati

ve %

dru

g re

leas

e

Time (min.)

Initial time

After 3 months

After 6 months

Figure 5 Drug release form optimized formulation (OFDT1) before and after storage.

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Formulation code Predicted Values (DT)

Exp. Values (DT)

Residual Predicted Values(Hardness)

Exp. Values (Hardness) Residual

CP1X1= +0.5X2= 1

22.64 21C1.02 1.6 4.59 4.3±0.98 0.29

CP2X1= +1X2= +0.5

23.74 22±1.14 1.74 4.58 4.4±1.01 0.18

Table 7: Comparison of Predicted Values and Experimental Values for Check Point Batches.

Number%MCC in MCC: Lactose combination

Ac-Di-Sol DT Hardness Desirability

1 69.00 4.39 25 4.5 1.000

Table 8: Predicted desirability.

Response Prediction S.D. SE (n=1) 95% PI low 95% PI high

DT 25 0.474342 0.569742 23.5355 26.4846

Hardness 4.5 0.075 0.08592777 4.30185 4.69815

Table 9: Predicted response at 95% confidence (n=1).

Sr no. Formulation Code Bulk density (mg/ml)

Tapped Density(mg/ml) Hausner’s Ratio Carr’s Index (%) Angle of Repose(

θ)1 OFDT 1 0.49±0.29 0.65±0.37 1.32±0.59 24.61±1.05 25.38±0.28

Table 10: Physical properties of optimized tablet blend*.

* Values given as mean±standard deviation (n=3).

Parameters* Thickness Diameter Weight Friability Drug Content Wetting time

Formulations (mm) (mm) (mg) (%) (%) (Seconds)

OFDT 1 3.9±058 9.0±0.38 250±1.49 0.29±1.58 99.98±1.78 15±0.88

Table 11: Characterization of optimized tablet (OFDT 1).

PredictedValues(Disintegration time)

ExperimentalValues(Disintegration time)

Predicted Values(Hardness)

Experimental Values(Hardness)

25±0.4743 24±0.91 4.50±0.085 4.4±0.42

Table 12: Characterization of optimized tablet (OFDT 1).

Pharmacokinetic parameter*

Formulation Cmax(ng/mL) Tmax(h) AUC0-t (ng/mL .h) AUC0- ∞ (ng/mL. h) Kel (1/h)

OFDT 1 32.5±1.62 1±1.89 266.60±4.09 309.2±5.042 0.225±1.13

Ondem MD 8 31.05±4.02 2±1.20 250.67±5.83 295.79±3.01 0.193±1.01

Table 13: Pharmacokinetic parameter of optimized FDT and marketed formulation.

*Values represented as mean±S.D (n=3)

Time period(months)

At 400C ± 20 C and 75±5% RH* 250C ± 20 C and 60 ± 5% RH**

OFDT1 OFDT1

0 4.4±0.68 4.4±0.68

3 4.2±0.79 4.3±0.49

6 4.1±0.58 4.2±0.44

Table 14: Effect of storage condition on hardness of prepared tablet.

Data are expressed as mean±S.D. (n = 3)

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Ac-Di-Sol, being a super disintegrant, enhances faster disintegration. In addition, combination of MCC and lactose also help in the disintegration process. It was observed form the response surface plot that the both the factors had influence on the DT and hardness of the tablets. Optimum value of hardness and DT was observed at high level of MCC in MCC: Lactose combination and at 4% concentration of Ac-Di-Sol. Thus, it was observed that the novel combination of a super disintegrant and a combination of diluents produced fast dissolving tablets having adequate mechanical strength and rapid disintegration.

Thus, the major problem in formulating mouth-dissolving tablets, i.e., poor mechanical strength, was overcome.

Pharmacokinetic study

Table 13 shows the result of pharmacokinetic analysis obtained after administration of optimized FDT (OFDT 1) and marketed formulation (Ondem MD 8), while plasma concentration profile for both formulation are shown in (Figure 4). Maximum plasma concentration after administration of marketed formulation and OFDT 1 was found to be 31.05 ng/ml and 32.5 ng/ml in 120 min. and 60 min. respectively. Shows quick on set of effect. The 90 % confidence intervals for AUC0-t (ng./mL. h), AUC0-∞ (ng./mL .h) and Cmax(ng/mL) for both the formulation were within 85-125% interval proposed by most regulatory agencies (FDA, EMEA, ANVISA). It was concluded that the two formulations are bioequivalent in their rate and extent of absorption and, thus, may be used interchangeably, without any prejudice of therapeutic effect. The one way ANOVA test showed statistically insignificant difference (p>0.05) between the AUC of optimized FDT and marketed formulation.

Stability study

Discoloration and liquefaction was not observed during

storage period. No significant change in hardness, disintegration time and drug content was observed as shown in (Table 14-16). From the result shown in (Table 14-16), it was concluded that formulations were stable and no significant change in the percentage drug content, hardness and disintegration time was to be observed. Effect of storage on drug release for optimized

The dissolution similarity (f2) was also calculated to compare before and after storage dissolution profile (Table 17). The f2 value was found to be more than 50, indicating a close similarity between both the dissolution profiles.

CONCLUSIONFastdissolving tablets of Ondansetron HCl having rapid

disintegration and good mechanical strength can be prepared using a novel combination of Ac-Di-Sol and Diluent (MCC: Lactose). A good evaluation of a statistical model is not how well it fits the data but how well it predicts the points. Comparison of predicted responses and observed values for the same showed close agreement, and the models were found to be valid. Hence, 3 level full factorial design and statistical models can be successfully used to optimize the formulations. The pharmacokinetic data revealed that the quick onset of effect was observed with optimized FDT and from the result of AUC it was concluded that optimized FDT was found to be bioequivalent in rate and extent of absorption. Thus this investigation conclusively demonstrates the potential role of fast dissolving tablet which meets therapeutic demand, manufacturing feasibility and excellent mechanical strength.

REFERENCES1. Salem II, Lopez, JMR, Galan AC. Ondansetron hydrochloride. In:

Analytical Profiles of Drug Substances and Excipients. Brittain HG, Editor; California, 2001; 301-308.

2. Biradar S, Bhagavati S, Kuppasad. Fast dissolving drug delivery

Time period(months)

At 400 C±20 C and 75±5% RH* 250C ± 20C and 60±5% RH**

OFDT1 OFDT1

0 99.98±0.66 99.98±0.66

3 99.94±0.51 99.43±0.67

6 99.00±0.89 99.12±0.23

Table 15: Effect of storage condition on drug content of optimized tablets.

Data are expressed as mean±S.D. (n = 3)

Time period(months)

At 400C ± 20C and 75±5% RH* 250C ± 20C and 60±5% RH**

OFDT1 OFDT1

0 24.00±0.51 24.00±0.51

3 24.5±0.22 24.5±0.43

6 24.2±0.38 24.7±0.61

Table 16: Effect of storage condition on disintegration time of optimized tablets.

Data are expressed as mean±S.D. (n = 3)

Formulations OFDT1 OFDT2

Time After 3 months After 6 months After 3 months After 6 months

f2 89 80 88 84

Table 17: f2 value for optimized formulations.

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Bhatt S, Sharma D, Mandge S, Sharma S, Jain V (2015) Design and Optimization of Taste Masked Fast Dissolving Tablet of Ondansetron Hcl using Full Factorial Design. J Drug Des Res 2(2): 1011.

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