INTRODUCTION:

Recently pharmaceutical industry has become increasingly aware of the need for the elderly be considered as a separate and unique medicare population. Though geriatric patients constitute a minor proportion of the population, its growth rate is high and hence will have a significant impact on the development of drug delivery systems¹.

An inability or unwillingness to swallow solid dosage forms such as tablets and the poor taste of medicines are some of the important reasons for consumer dissatisfaction^2,3. Levocetirizine is a selective, long-acting peripheral H₁ receptor antagonist, used in the treatment of Allergic rhinitis⁴.

Ion exchange resins are water insoluble, cross linked polymer containing salt forming groups in repeating position on the polymer chain. The unique advantages of Ion exchange resins for complexation are due to the fixed positively or negatively charged functional groups attached to water insoluble polymer backbones. These groups have an affinity for positively charged counter ions, thus absorbing the ions into the polymer matrix. Since most of the drugs possess ionic sites in their molecules, the resins charge provides to loosely bind such drugs. The binding is generally an equilibrium process, resulting in continuous desorption or elution of the drug from the resin as a drug is absorbed into the body⁴. Ion exchange resins are high molecular weight water insoluble polymers and so are not absorbed by the body and therefore inert and safe for oral use. The complex of cationic drugs and weak ion exchange resin does not break at the pH of saliva which is 6-7 with cation concentration in the stomach and pH 1.2, free drug is immediately released. This implies that while passing through the mouth the drug remains in complex form, thereby imparting no bitter taste in the mouth. This property was exploited to formulate consumer-friendly dosage forms i.e., oro dispersible tablets. These dosage forms are placed in the mouth and allowed to disperse in the saliva, to produce a suspension that can be easily swallowed by the patient. The advantage of this convenient administration has encouraged both academics and industries to generate new fast disintegrating formulations. Less frequently, they are designed to be absorbed through the buccal and esophageal mucosa as the saliva passes into the stomach. In the latter case, the bioavailability of a drug from fast dispersing formulations may be even greater than that observed for standard dosage forms. Lende et al. developed mouth desolving formulation of Astemizole using disintegrants such as Crosscarmellose, Crosspovidone and Indion 414 for antiallergic action⁵. Likewise till now many attempts has been made for formulating oro dispersible tablets using Labetalol HCl⁶, Croscarmellose sodium⁷ natural disintegrants⁸, etc. each has their own advantages and disadvantages. These formulations become more popular when European Pharmacopoeia adopted the term “Oro dispersible Tablet” for the tablet to be placed in the mouth that disperses rapidly before swallowing^9,10.

The main objective of the study was to formulate taste masked oral dispersible tablets of Levocetirizine by direct compression technique and their evaluation. In the present work, an attempt was made to formulate taste masked Levocetirizine oro- dispersible tablet using different superdisintegrants (like Sodium starch glycolate, Avicel PH102 and Low Hydroxy Propyl Cellulose in variable concentrations by direct compression method. The fundamental principle used in the development of the fast-dissolving tablet is to enhance absorption and improve the bioavailability of the drug¹¹.

MATERIALS AND METHODS:

The active pharmaceutical ingredient Levocetirizine dihydrochloride was procured from Aarti drugs Ltd Mumbai, India. Tulsion-339 was supplied by Thermax Ltd Pune, India and analytical grade Sodium Starch Glycolate, Microcrystalline cellulose and L-HPC from Dr. Reddy’s lab Hyderabad, India.

METHODS:

Calibration Curve for Levocetirizine in 0.1N HCL:

An accurately weighed 50mg of Levocetirizine dihydrochloride was dissolved in 100ml of 0.1N HCl to get a concentration of 500µg/ml. From this stock solution aliquot with suitable dilutions were made in order to get concentrations in between the Beer’s range of 8-24µg/ml. The absorbance was measured at 230.1 nm by using a UV-visible spectrophotometer (Thermo Spectronic, USA.Model - Genesys 6). A graph of concentration vs. absorbance was plotted and shown in fig 1.

Drug-excipient interaction studies:

Infrared (IR) Spectroscopy studies were used for the evaluation of physicochemical compatibility and interactions, which helps in the prediction of the interaction of the drug with polymers. Positive interactions sometimes have a beneficial effect as far as desired release parameters are concerned. Therefore, in the present studies, Levocetirizine Dihydrochloride with the given polymers was analyzed for compatibility study. The spectra are shown in figure 2– 6.

Preparation of Drug-Resin Complex^12,13,14:

Drug-resinates were prepared using the batch method. The resins were first washed with distilled water. Made 5% slurry of the resin in the deionized water and stirred for half an hour to swell the resin. Added required amount of drug in the ratio 1:4 (Drug: Polymer) in this slurry under stirred conditions. After the complete addition, kept stirring for around 4 to 8 hours so that most of the drug gets complexed with the resin. Filtered the drug-resinates so formed through Whatman filter paper. Washed the drug-resinates with distilled water and dried at about 60^oC under a vacuum. The drug content in the filtrate was analyzed by ultraviolet (UV) spectroscopy at 230.1nm. The amount of drug loaded on the complexes was obtained by subtracting the remaining amount of drug in the filtrate from the initial amount.

Formulation of Tablets:

Granules of drug-resinate earlier obtained were mixed/blended with super disintergrant cellactose as a diluent, spray dried mannitol as mouth feel enhancer, aspartame as sweetener, vanillin as a flavoring agent, talc as a glidant and magnesium stearate as lubricant. All ingredients were passed through mesh # 60. Before compression, hardness was adjusted. Drug-resinate equivalent to 5mg of Levocetirizine dihydrochloride was compressed on 10- station rotary punching machine (RIMEK INDIA) to get tablets, each weighing 100mg. Table 1 shows the compositions of F1-F9 formulations.

Pre-Compression Parameters^15,16

All the physical parameters namely, angle of repose, bulk density, and compressibility index were performed and the results are shown in Table 2.

1. Angle of Repose:

It is the maximum angle possible between the surface of a pile of powder and the horizontal plane. The angle of repose was determined by the funnel method. Accurately weighed powder blend was taken in the funnel. Height of the funnel was adjusted in such a way the tip of the funnel just touched the apex of the powder blend. Powder blend was allowed to flow through the funnel freely onto the surface. Diameter of the powder cone was measured and the angle of repose was calculated using the given formula.

ø = tan^-1 (h/r)

2. Bulk density:

It is the ratio of the total mass of powder to the bulk volume of powder. Required quantity of powder blend was transferred in a 100 ml graduated cylinder and the bulk density was calculated by using the formula given below.

Weight of powder

Bulk density = ––––––––––––––––

Bulk volume

3. Percentage Compressibility:

Percent compressibility of the powder mix was determined by Carr’s Compressibility index calculated by the following formula.

TBD – LBD

Carr’s Index % = –––––––––––– x 100

TBD

Ii. Post-compression Parameters^{15,17,18,19,20}

1. Shape and color of tablets: Uncoated tablets were examined under a lens for the shape of the tablet and color was observed by keeping the tablets in light.

2. Uniformity of thickness:

Three tablets were picked from each formulation randomly and thickness was measured individually. It is expressed in mm and the standard deviation was also calculated. The tablet thickness was measured using a dial caliper (Mitutoyo, Japan).

3. Hardness test:

Hardness of the tablet was determined by using the Monsanto hardness Tester-Mumbai. The lower plunger was placed in contact with the tablet and a zero reading was taken. The plunger was then forced against a spring by turning a threaded bolt until the tablet fractured. As the spring was compressed a pointer ride along a gauge in the barrel to indicate the force.

4. Friability test:

This test is performed to evaluate the ability of tablets to withstand abrasion in packing, handling and transporting. Initial weight of 20 tablets is taken and these are placed in the Roche friabilator, rotating at 100rpm for 4min. The tablets are then taken out, dedusted and weighed. The difference in the weight is noted and expressed as a percentage

5. Wetting Time:

Circular tissue papers were placed in a Petri dish containing water. The prepared tablet was then carefully placed. The time required for water to reach the upper surface of the tablets and to get completely wet was noted as the wetting time. Wetting time was recorded using a stopwatch.

6. Water Absorption Ratio²¹:

A piece of tissue paper folded twice was placed in a small Petri dish containing 6ml of distilled water. A tablet was put on the paper and time required for complete wetting was measured. The wetted tablet was then weighed. Water absorption ratio, R, was determined using the equation

R = 100 x Wa – Wb/Wb

Where,

Wb = weight of the tablet before water absorption

Wa = weight of the tablet after water absorption

Three tablets from each formulation were performed and standard deviation was also determined¹².

7. Content Uniformity²²:

Two tablets were weighed and powdered. The whole amount of powdered tablet was transferred into a 100ml volumetric flask. Add 0.1N HCl up to the mark. After a few minutes the solution was filtered; rejecting first few ml of the filtrate. 10ml of filtrate was taken in a 50ml volumetric flask and diluted up to the mark with 0.1N HCl and analyzed spectrophotometrically at 230.1nm. The concentration of Levocetirizine dihydrochloride (in µg/ml) was calculated by using the standard Calibration curve of Levocetirizine dihydrochloride. Drug content claim was 5mg per tablet. This procedure was followed for 10 tablets from each formulation. The mean and standard deviation values were also calculated.

8. In- Vitro Disintegration Time:

In- vitro disintegration time was measured by dropping a tablet in a beaker containing phosphate buffer PH 6.8. Tablets from each formulation were randomly selected and in vitro dispersion time was performed. All these studies were performed and the results are shown in table 3.

9. In vitro Dispersion Time:

In vitro dispersion time was measured by dropping a tablet in a measuring cylinder containing 6ml of pH 6.8 (simulated saliva fluid). Three tablets from each formulation were randomly selected and in vitro dispersion time was performed. Standard deviation was also determined and in vitro dispersion time is expressed in Seconds¹³.

9. In-vitro drug release studies:

In-vitro drug release studies were carried out by using USP-XXIII dissolution apparatus 900ml of 0.1NHCL (500ml) was placed in the dissolution flask maintained at a temperature of 37±1⁰C. One tablet was placed in the flask of the dissolution apparatus and was operated to run up to 15mins at 50rpm. At definite time intervals, 10 ml of dissolution medium was withdrawn, filtered and again replaced with 10ml of fresh medium. Suitable dilutions were done with dissolution medium and were analyzed spectrophotometrically at λmax is 230.1nm using a UV-spectrophotometer. The in-vitro drug release of ODT tablets of Levocetirizine were shown in Table 4 and their comparison profile was shown in fig 5.

10. Stability Studies:

ICH specifies the length of study and storage conditions: long-term testing 25±2⁰C/60% ±5% RH for 12 months Accelerated testing 40±2⁰C/75% ±5% RH for 6 months Stability studies were carried out at 25⁰C/60% RH and 40⁰C/75% RH for a specific time period up to 30 days for selected formulations^23,24.

For determining interactions between the active pharmaceutical ingredient and polymers, FT-IR studies were undertaken. The FT-IR spectra are shown in Figures 2 to 6.

I) Pre-compression Parameters:

Angle of Repose, Bulk Density, Percentage Compressibility:

All formulations showed the angle of repose within 24^OC. It indicates that all formulations showed good flow properties. The values obtained lie within the acceptable range and no large differences were found between loose bulk density and tapped bulk density. This result helps in calculating the % compressibility of the powder. The percent compressibility for all nine formulations lies within the range of 11.53 to 15.38%.

II) Post-compression Parameters:

1. Shape and Color of Tablets:

Tablets showed flat, circular shapes in white color. There was no change in the color and odor of the tablets in all the formulations. It indicates that all the excipients used were compatible with the drug and did not cause any chemical reaction that affects the properties of the formulation.

2. Thickness Test:

The mean values are shown in Table 3 The values are almost uniform in all formulations. Thickness was found in the range from 2.9±0.01mm to 2.9±0.04mm respectively.

3. Hardness Test:

The results of hardness are given in Table 3. A hardness test was performed by a Monsanto tester. Hardness was maintained to be within 3.1kg/cm² to 3.7kg/cm², as these tablets are orodispersible.

4. Friability Test:

The study results tabulated in Table 3 were found well within the approved range (<1%) in all the formulations. Results revealed that the tablets possess good mechanical strength.

5. Weight Variation Test:

The percentage weight variation for all the formulations is tabulated in Table 3. All the tablets passed the weight variation test as the % weight variation was within the pharmacopeial limits of ±10%.

6. Drug Content Uniformity: The drug content of the tablets was found between 4.775±0.120mg to 4.912 ±0.135mg of Levocetirizine dihydrochloride. The results indicated that in all the formulations the drug content was uniform.

7. Wetting Time:

The record of the wetting time was shown in Table 4. The wetting time in all the formulations was very fast. This may be due to the ability of swelling and also the capacity of absorption of water. MCC and starch glycolate absorbs water rapidly in the formulations and shows fast wetting time.

8. Water Absorption Ratio:

The water absorption ratio results are tabulated in Table 4 The ratio values of formulations found in the range of 84.61 to 92.00. In the case of tablets containing LHPC, caused a great deal of swelling. In this, as the quantity of L-HPC increased, the water absorption also increased due to the high swelling property. So, the water absorption ratio value of formulation 9 was high.

9. In vitro Disintegration Time:

Sodium Starch Glycolate has high water uptake and swelling pressure which leads to faster disintegration. MCC has porosity less than L-HPC. At Low porosities, disintegration time decreases rapidly with the increased MCC content. So, the disintegration time of tablets containing L-HPC was more as compared to that of tablets containing MCC.

10. In vitro Dispersion Time:

The values obtained are recorded in Table 5. In vitro dispersion time is measured by the time taken to undergo uniform dispersion. Rapid dispersion within seconds was observed in all the formulations.

11.In vitro Dissolution Studies:

In the comparative study for the formulations F3, F6, F9 release 96.36%, 90.03%, 83.89% respectively at the end of 15 minutes, and the graphical representation is shown in figure 16. To know the order of release the release rates were subjected to kinetic studies. Next, the model fitting of the release profiles was performed using PCP DISSO-V2 software to observe the mechanism. The correlation coefficient values obtained for all five models are tabulated in Table 8. The formulations F1, F2, F3, F5, and F6 show Higuchi Matrix which describes the drug release, as a diffusion process based on Fick’s law, square root time dependent. And other formulations showed the Hixson Crowell model which has been used to describe the dissolution that occurs in planes that are parallel to the drug surface if the tablet dimensions diminish proportionally, in such a manner that the initial geometrical form keeps constant all the time.

12. Stability Studies:

The formulations F3, F6, F9 were selected for stability studies on the basis of their high cumulative % drug release and the also results of in vitro disintegration time, wetting time, and in vitro dispersion studies. The results obtained are tabulated in Table 9 and Table 10. From these results, it was concluded that formulations F3, F6, F9 are stable and retained their original properties.

Table 2: Pre-Compression parameters of Levocetirizine Dihydrochloride tablet formulation

Formulation code	Angle of Repose (q)	Loose Bulk Density (gm/cm³)	Tapped Bulk Density (gm/cm³)	% Compressibility
F1	18.56	0.46	0.53	13.20
F2	18.43	0.47	0.54	12.96
F3	18.00	0.46	0.52	11.53
F4	22.29	0.59	0.69	14.00
F5	21.18	0.57	0.66	13.63
F6	18.26	0.54	0.62	12.90
F7	23.13	0.55	0.65	15.38
F8	21.80	0.53	0.62	14.51
F9	20.80	0.52	0.60	13.33

Table 3: Post Compression Parameters of Levocetirizine Dihydrochloride ODT

Formulation Code	Uniformity of Thickness (n=3) (mm)	Hardness (n=3) (kg/cm²)	Friability % (n=10)	Uniformity of Weight (n=20) (mg)	Drug Content (n=3) (mg)
F1	2.9. ± 0.01	3.4 ± 0.25	0.3296	99.95 ± 1.011	4.912 ± 0.135
F2	2.9. ± 0.02	3.3 ± 0.27	0.2988	99.95 ± 1.120	4.875 ± 0.104
F3	2.9. ± 0.04	3.1 ± 0.25	0.2985	100.3 ± 1.123	4.900 ± 0.077
F4	2.9. ± 0.01	3.5 ± 0.23	0.3788	101.0 ± 1.775	4.795 ± 0.160
F5	2.9. ± 0.02	3.5 ± 0.24	0.3485	100.05 ± 1.00	4.800 ± 0.22
F6	2.9. ± 0.03	3.5 ± 0.26	0.2993	100.55 ± 1.11	4.825 ± 0.011
F7	2.9. ± 0.04	3.7 ± 0.24	0.3791	100.55 ± 1.15	4.775 ± 0.13
F8	2.9. ± 0.03	3.6 ± 0.24	0.3492	105.25 ± 1.5	4.800 ± 0.110
F9	2.9. ± 0.04	3.6 ± 0.24	0.3296	104.00 ± 1.80	4.775 ± 0.120

Table 6: In vitro dissolution profile of the formulations F1, F2, F3, F4

Formulation code

Time (min)

Absorbance at 230.1nm

Conc. in mg/ml

Conc. in 500 ml(mg)

CLA (mg)

Cum. Drug Released (mg)

Cum. % Drug Released

Cum. % Drug Retained

Log Cum. % Drug Retained

0.203

0.216

0.232

0.244

0.262

6.591

7.013

7.532

7.922

8.506

3.295

3.506

3.766

3.961

4.253

0.000

0.066

0.136

0.211

0.291

3.295

3.572

3.902

4.172

4.544

65.909

71.448

78.045

83.448

90.877

34.091

28.552

21.955

16.552

9.123

1.533

1.456

1.342

1.219

0.960

0.207

0.220

0.237

0.254

0.271

6.721

7.143

7.695

8.247

8.799

3.360

3.571

3.847

4.123

4.399

0.000

0.067

0.139

0.216

0.298

3.36

3.639

3.986

4.339

4.697

67.208

72.773

79.721

86.779

93.948

32.792

27.227

20.279

13.221

6.052

1.516

1.432

1.307

1.121

0.782

0.210

0.226

0.243

0.261

0.278

6.818

7.338

7.89

8.474

9.026

3.409

3.669

3.945

4.237

4.513

0.000

0.068

0.142

0.220

0.305

3.409

3.737

4.086

4.457

4.818

68.182

74.74

81.727

89.149

96.364

31.818

25.260

18.273

10.851

3.636

1.503

1.402

1.262

1.032

0.561

0.198

0.209

0.226

0.237

0.251

6.387

6.742

7.290

7.645

8.097

3.194

3.371

3.645

3.823

4.048

0.000

0.064

0.131

0.204

0.281

3.194

3.435

3.776

4.027

4.329

63.871

68.697

75.529

80.535

86.581

36.129

31.303

24.471

19.465

13.419

1.558

1.496

1.389

1.289

1.128

Amount of drug present in one tablet F1 = 4.912mg, F2 = 4.875mg, F3 = 4.900mg, F4 = 4.

Table 7: In vitro dissolution profile of the formulations F5, F6, F7, F8, F9

Time

(min)

Absorbance at 230.1nm

Conc. in mg/ml

Conc. in 500ml(mg)

CLA (mg)

Cum. Drug Released(mg)

Cum. % Drug Released

Cum. % Drug Retained

Log Cum. % Drug Retained

0.201

0.219

0.229

0.241

0.255

6.484

7.065

7.387

7.774

8.226

3.242

3.532

3.694

3.887

4.113

0.000

0.065

0.135

0.209

0.287

3.242

3.597

3.829

4.096

4.400

64.839

71.942

76.581

81.929

88.000

5.161

28.058

23.419

18.071

12.000

1.546

1.448

1.370

1.257

1.079

0.205

0.223

0.231

0.247

0.261

6.613

7.194

7.452

7.968

8.419

3.306

3.597

3.726

3.984

4.210

0.000

0.066

0.138

0.213

0.292

3.306

3.663

3.864

4.196

4.502

66.129

73.258

77.277

83.929

90.039

33.871

26.742

22.723

16.071

09.961

1.530

1.427

1.356

1.206

0.998

0.194

0.203

0.211

0.221

0.226

6.258

6.548

6.806

7.129

7.290

3.129

3.274

3.403

3.565

3.645

0.000

0.063

0.128

0.196

0.267

3.129

3.337

3.531

3.761

3.913

62.581

66.735

70.626

75.213

78.252

37.419

33.265

29.374

24.787

21.748

1.573

1.522

1.468

1.394

1.337

0.196

0.205

0.214

0.228

0.235

6.323

6.613

6.903

7.355

7.581

3.161

3.306

3.452

3.677

3.790

0.000

0.063

0.129

0.198

0.272

3.161

3.370

3.581

3.876

4.062

63.226

67.394

71.619

77.516

81.245

36.774

32.606

28.381

22.484

18.755

1.566

1.513

1.453

1.352

1.273

0.198

0.209

0.216

0.230

0.243

6.387

6.742

6.968

7.419

7.839

3.194

3.371

3.484

3.710

3.919

0.000

0.064

0.131

0.201

0.275

3.194

3.435

3.615

3.911

4.195

63.871

68.697

72.303

78.213

83.890

36.129

31.302

27.697

21.787

16.110

1.558

1.496

1.442

1.338

1.207

Amount of drug present in one tablet F5 4.800mg, F6 = 4.825mg, F7 = 4.775mg, F8 = 4.800mg, F9 = 4.775 mg

Table 8: Model fitting of the release profile using five different models (R-value)

Formulation Code	Mathematical Models. (Kinetics)
Formulation Code	Zero order	First order	Higuchi matrix	Peppas	Hixson crowell	Best fit model
F1	0.8317	0.9718	0.9885	0.9759	0.9852	HIGUCHI MATRIX
F2	0.8401	0.9631	0.9874	0.9733	0.9813	HIGUCHI MATRIX
F3	0.8436	0.9505	0.9907	0.9790	0.9769	HIGUCHI MATRIX
F4	0.8260	0.9877	0.9908	0.9777	0.9937	HIXSON CROWELL
F5	0.8207	0.9866	0.9950	0.9877	0.9938	HIGUCHI MATRIX
F6	0.8233	0.9793	0.9910	0.9817	0.9890	HIGUCHI MATRIX
F7	0.7872	0.9978	0.9950	0.9834	0.9987	HIXSON CROWELL
F8	0.8025	0.9925	0.9888	0.9736	0.9950	HIXSON CROWELL
F9	0.8094	0.9819	0.9829	0.9671	0.9880	HIXSON CROWELL

Table -9: Selected formulations for stability studies F3, F6 and F9 stored at 25⁰c/60%RH

Formulation Code	Tested after time (in days)	Hardness (kg/cm²)	Disintegration time (sec)	Wetting time (sec)	Drug content (n=5)	Friability %
Formulation Code	Tested after time (in days)	*Mean* ± *SD (n=3)*			Drug content (n=5)	Friability %
F3	10	3.2±0.25	28.70±0.430	48.00±0.19	4.900±0.78	0.2986
	20	3.2±0.28	28.43±0.230	49.00±0.20	4.900±0.60	0.2987
	30	3.1±0.26	28.20±0.330	48.30±0.18	4.900±0.75	0.2988
F6	10	3.3±0.29	30.30±0.515	49.30±0.40	4.825±0.80	0.2993
	20	3.4±0.30	30.45±0.560	48.00±0.44	4.825±0.85	0.2994
	30	3.5±0.26	30.31±0.587	49.60±0.48	4.825±0.84	0.2994
F9	10	3.6±0.36	32.10±0.450	50.00±0.56	4.775±0.89	0.3296
	20	3.5±0.28	32.40±0.435	51.00±0.60	4.774±0.88	0.3297
	30	3.6±0.27	32.66±0.467	51.30±0.58	4.775±0.86	0.3298

Table 10: Selected formulations for stability studies F3, F6 and F9 stored at 40⁰c/75% RH

Formulation Code	Tested after time(in days)	Hardness(kg/cm²)	Disintegration time(sec)	Wetting time(sec)	Drug content(n=5)	Friability %
Formulation Code	Tested after time(in days)	*Mean* ± *SD (n=3)*
F3	10	3.21±0.25	29.20±0.432	46.00±0.18	4.890±0.79	0.2988
	20	3.21±0.28	29.10±0.231	47.00±0.21	4.775±0.62	0.2990
	30	3.20±0.26	29.02±0.334	48.00±0.20	4.890±0.78	0.2989
F6	10	3.62±0.29	31.30±0.520	47.00±0.42	4.750±0.87	0.2995
	20	3.64±0.30	31.33±0.570	48.00±0.45	4.699±0.89	0.2997
	30	3.66±0.26	31.55±0.590	49.00±0.47	4.800±0.91	0.2999
F9	10	3.71±0.36	33.56±0.455	49.00±0.58	4.700±0.90	0.3299
	20	3.72±0.28	33.60±0.445	50.00±0.62	4.695±0.92	0.3298
	30	3.74±0.27	33.62±0.470	51.00±0.64	4.778±0.93	0.3299


Figure 7: Comparative in vitro release profile of Levocetirizine orodispersible tablets according to Zero Order Kinetics for formulation F-1, F-2 and F-3.	Figure 8: Comparative in vitro release profile of Levocetirizine orodispersible tablets according to Zero Order Kinetics for formulation F-4, F-5 and F-6.

Figure 9: Comparative in vitro release profile of Levocetirizine orodispersible tablets according to Zero Order Kinetics for formulation F-7, F-8 and F-9.	Figure 10: Comparative in vitro release profile of Levocetirizine orodispersible tablets according to Higuchi Matrix for formulation F-1, F-2 and F-3.

Figure 11: Comparative in vitro release profile of Levocetirizine orodispersible tablets according to Higuchi Matrix for formulation F-4, F-5 and F-6.	Figure 12: comparative in vitro release profile of levocetirizine orodispersible tablets according to Higuchi Matrix for formulation F-7, F-8 and F-9.

Figure 13: comparative in vitro release profile of Levocetirizine orodispersible tablets according to Hixson Crowell for formulation F-1, F-2 and F-3.	Figure 14: Comparative in vitro release profile of Levocetirizine orodispersible tablets according to Hixson Crowell for formulation F4, F5 and F6

Figure 15: Comparative in vitro release profile of Levocetirizine orodispersible tablets according to Hixson Crowell for formulation F-7, F-8 and F-9	Figure 16: Comparative in vitro release profile of Levocetirizine orodispersible tablets for formulation F-3, F-6 and F-9

Formulation Code	Wetting Time (n=3)	Water Absorption Ratio (n=3)
Formulation Code	*Mean* ± SD	*Mean* ± SD
F1	51 ± 1.06	84.61 ± 0.23
F2	50 ± 1.17	86.73 ± 0.12
F3	48 ± 0.15	89.76 ± 1.12
F4	52 ± 1.09	87.00 ± 0.89
F5	51 ± 1.07	88.00 ± 0.24
F6	49 ± 1.23	90.00 ± 0.91
F7	53 ± 1.04	89.10 ± 0.85
F8	52 ± 0.30	90.50 ± 0.32
F9	51 ± 1.05	92.00 ± 0.45

Formulation Code	*In vitro* Disintegration Time (Sec)	*In vitro* Dispersion Time (sec.)
F1	32 ± 1.081	45 ± 1.15
F2	30 ± 0.200	43 ± 0.40
F3	28 ± 0.500	41 ± 0.55
F4	36 ± 0.225	54 ± 0.60
F5	34 ± 0.420	53 ± 0.80
F6	30 ± 0.320	50 ± 0.90
F7	38 ± 0.625	56 ± 1.20
F8	37 ± 0.450	54 ± 0.95
F9	32 ± 0.340	51 ± 0.75

Ingredients

Mannitol

Aspartame

Vanillin

Ingredients	Formulation code (mg)
Ingredients	F1	F2	F3	F4	F5	F6	F7	F8	F9
Levocetirizine Dihydrochloride +Tulsion339 (1:4)	25	25	25	25	25	25	25	25	25
Sodium starch glycolate	2	3	4	--	--	--	--	--	--
Avicel PH 102	--	--	--	2	3	4	--	--	--
Low hydroxyl propyl cellulose	--	--	--	--	--	--	2	3	4
Cellactose	57.02	56.02	55.02	57.02	56.02	55.02	57.02	56.02	55.02
Mannitol	13.33	13.33	13.33	13.33	13.33	13.33	13.33	13.33	13.33
Aspartame	0.66	0.66	0.66	0.66	0.66	0.66	0.66	0.66	0.66
Vanillin	0.66	0.66	0.66	0.66	0.66	0.66	0.66	0.66	0.66
Magnesium stearate	0.50	0.50	0.50	0.50	0.50	0.50	0.50	0.50	0.50
Talc	0.83	0.83	0.83	0.83	0.83	0.83	0.83	0.83	0.83