1. INTRODUCTION:

Bilastine is a new second-generation H1-antihistamine approved for the symptomatic treatment of allergic rhino-conjunctivitis and chronic urticaria (CU). Bilastine, with its efficacy and safety profile, optimizes the evaluation of research on anti-histamine it works by blocking histamine receptors.

Orodispersible tablets of bilastine were prepared using cross povidone, mannitol as a super disintegrant and aerosil, magnesium stearate by direct compression method by using taste masking by organoleptic method². Flavor masking is the apparent elimination of an unpleasant taste that would otherwise be there. The ideal way to lessen or suppress bitterness would be to find a universal inhibitor of all bitter-tasting compounds that does not interfere with other taste modalities, such as sweetness or saltiness³. A number of novel, cutting-edge methods have recently been established for the formulation of orodispersible tablets¹.

In this paper, we reported the formulation optimization and evaluation of novel Orodispersible tablets of bilastine an anti-histamine commonly used to prevent rhino-conjunctivitis and urticaria in allergic conditions. It is a moderately bitter drug therefore essential to mask the bitter taste⁴. ODTs have proven their ability to enhance patient compliance because they disintegrate in the mouth and there is no need to swallow a whole tablet. The Orodispersible tablet can be prepared by using a variety of technologies including the direct compression method. The key advantages of the direct compression method are accurate dosing, rapid drug therapy interventions, patient compliance, ease of administration, enhanced palatability, easy to handle, etc⁵. A large number of super disintegrants are used in the fabrication of Orodispersible tablets. These include crospovidone, croscarmellose sodium, sodium starch glycolate, etc. ODTs were prepared by various methods like direct compression, sublimation method, effervescent method, etc. Each method has its advantages and disadvantages but most frequently direct compression is used in preparing Orodispersible tablets by utilization of 2³ factorial designs and a central composite design in a quadratic mode⁷.

The purpose of this study was to develop a novel formulation of ODTs for the treatment of rhino-conjunctivitis and urticaria prepared by direct compression method and containing a combination of different super disintegrants; the later taste masked by the use of a combination of different sweetening and flavoring agents like orange and peppermint flavors⁸. Taste is an important parameter in administering drugs orally. One of the significant formulation issues with many medications is unpleasant to taste. A major concern for medical professionals is how to administer bitter medications orally while maintaining an appropriate level of palatability. The polymer coating approach has been described as an effective taste masking strategy, although the organoleptic method may also be used to hide the flavor of the active substance. Formulation of ODTs manufactured by taste masking using an organoleptic method employing direct compression as a traditional technology and a mix of different sweetening and flavoring chemicals, such as orange and peppermint flavors. Successful taste masking of bilastine was done by organoleptic method and prepared ODTs of bilastine were by using different super disintegrants by direct compression method. Then rapid disintegration is occurred due to penetration of saliva into the pores, which leads to swelling of asuper disintegrant to create enough hydrodynamic pressure for quick and complete disintegration of the ODTs¹.

2. MATERIALS AND METHODS:

2.1 Material:

Bilastine was obtained from Medley Pharma Ltd., Andheri. CCS, CP, SSG and MCC were received as gift samples from Medley Pharma Ltd., Andheri. Other excipients and chemicals used were of AR grade.

2.2 Experimental Design:

Central composite design (CCD) was used for experimental design containing two independent variables crospovidone (X1) and MCC PH 102 (X2) were investigated at three levels as low, medium and high given in table 1. While putting the values nine baches were generated using DoE software (version 13). In that independent variables were investigated in the response i.e. percentage drug release (Y1), disintegration time (Y2), and wetting time (Y3). The statistical experimental design was evaluated through the analysis of variance (ANOVA) test using the Design Expert software (Version 13).

Table 1: Independent Variables and their Levels of Central Composite Design

Independent Variable	Unit	Levels
Independent Variable	Unit	-ᾱ	Low	Medium	High	+ᾱ
Crospovidone	%	1.414	2	3.5	5	6.141
MCC-PH-102	%	1.414	39	42	45	46.24

2.3. Pre-formulation Studies:

Pre-formulation studies such as physical appearance, solubility, melting point, hygroscopicity and drug excipient compatibility were performed to confirm the suitability and stability of drug and excipient for the formulation of mouth dissolving tablets¹¹.

2.3.1 Pre-compression parameter:

1) Bulk Density: Bulk density is the ratio of a given mass of powder and its bulk volume. Bulk density was determined by measuring the volume of a known mass of powder sample that has been passed through the screen into a graduated cylinder or through a volume measuring apparatus into a cup¹⁵.

Bulk Density=W/V₀

Where, W=Weight of powder in gm

V₀=Bulk Volume of powder in ml

2) Tapped Density:

Tapped Density = W/V_f

In which W=Weight of the powder

Vf=Tapped volume of the powder²⁰.

3) Carr’s/Compressibility Index:

The compressibility Index is an important measure to calculate the flow ability of powders. It is represented as a percentage.

Compressibility [%] = Tapped density – Bulk density/Tapped density x 100)

4) Hausner’s Ratio:

It indicates the flow properties of the powder and is measured by the ratio of tapped density to bulk density.

Hausner"s ratio = Tapped density / Bulk density

5) Angle of Repose (^θ):

Angle of repose is defined as the maximum angle possible between the surface of a pile of the powder and horizontal plane. The frictional force in loose powder or granules can be measured by the angle of repose¹⁴.

θ = tan ^-1 (h/r)

Where, θ = angle of repose,

h = height of the pile,

r = radius of the pile base

2.3.2 Determination of UV Spectrum:

Bilastine Solution (10 µg/ml) was prepared in phosphate buffer pH 6.8. This solution was scanned under a double-beam UV visible Spectrophotometer (Shimadzu-1800) and the spectrum was recorded in the wavelength ranges between 200-400 nm.

2.3.3 Preparation of Calibration Curve of Bilastine:

Calibration curve of bilastine in phosphate buffer pH. 6.8 was established by preparing different dilutions of the drug like 5, 10, 15, 20, and 25 µg/ml from a stock solution of 10mg/100ml and taking the absorbance of these solutions was measured spectrophotometrically at λmax 281nm. Also, plotted the graph of absorbance of bilastine against concentration in MS Excel and determined the slope and intercept.

2.3.4. Fourier Transform Infrared Spectroscopy (FTIR):

The FTIR studies were carried out using FTIR 1-S Affinity used to identify any drug and excipients interaction. The infrared spectra of bilastine, and a mixture of drugs and excipients that examined using FTIR.

2.3.5. Differential Scanning Calorimetry (DSC):

DSC analysis was used to measure melting temperature and also to check the possibility of any interaction between drug and excipients used in the formulation of tablets.

2.4. Preparation of Orodispersible Tablets:

Orodispersible tablets of bilastine were prepared by taste masking of bilastine by an organoleptic method using direct compression as conventional technology. The organoleptic method involves the addition of a combination of sweeteners (sucralose, aspartame) and flavors (orange, mint) to mask the unpleasant taste of low to moderately bitter bilastine⁹.

During direct compression, various super disintegrants were added like CCS,SSG and Crosspovidone (Table 2).

Table 2: Formulation Table of Optimized Batches of Bilastine ODTs

Sr. No.	Ingredients	BLS1	BLS2	BLS3	BLS4
1	Bilastine	20	20	20	20
2	MCC PH 102	84	75	90	92.48
3	Pearlitol SD 200	72.76	86	68	68.52
4	Sucralose	2	2	2	2
5	Aspartame	2	2	2	2
6	Crospovidone	11.24	7	10	7
7	Orange Flavour	3	3	3	3
8	Peppermint Flavour	3	3	3	3
9	Magnesium Stearate	1	1	1	1
10	Aerosil	1	1	1	1
	Average Weight (mg)	200	200	200	200

Table 2: continued

Sr. No.	Ingredients	BLS5	BLS6	BLS7	BLS8	BLS9
1	Bilastine	20	20	20	20	20
2	MCC PH 102	84	90	84	78	78
3	Pearlitol SD 200	81.26	74	77	80	86
4	Sucralose	2	2	2	2	2
5	Aspartame	2	2	2	2	2
6	Crospovidone	2.74	4	7	10	4
7	Orange Flavour	3	3	3	3	3
8	Peppermint Flavour	3	3	3	3	3
9	Magnesium Stearate	1	1	1	1	1
10	Aerosil	1	1	1	1	1
	Average Weight (mg)	200	200	200	200	200

2.5. Post Compression Parameter of Orodispersible Tablet of Bilastine:

The compressed tablets were evaluated for the tests such as weight variation, thickness, hardness, friability, disintegration time and in-vitro dissolution rate as per the pharmacopeial standards. Also, specific tests for the evaluation of mouth-dissolving tablets like wetting time and water absorption ratio were performed.

1) Weight Variation Test:

For the weight variation test as per the official book, USP was carried out. Twenty tablets were taken and their weight was determined individually and collectively using a single-pan electronic balance. The average weight of the tablets was determined from the collective weight. From the individual tablets weight, the range and percentage standard deviation were calculated. No more than 2 tablets should deviate from the average weight of the tablet showed the maximum percentage ± 10 mg deviation allowed according to USP¹².

2) Thickness

A vernier caliper was used to measure the thickness of each tablet¹⁴.

3) Hardness Test

The strength of the tablet is expressed as tensile strength (Kg/cm²). The tablet crushing load is the force required to break a tablet into pieces by compression. It was measured by using a tablet hardness tester (Monsanto hardness tester). Three tablets from each formulation batch were tested randomly and the average readings were noted^16,30.

4) Friability

The friability of the tablets was determined using a Roche friabilator. This device consists of a plastic chamber that is set to revolve around 25 RPM for 4 min dropping the tablets at a distance of 6 inches with each revolution. Pre-weighed a sample of 20 tablets was placed in the friabilator and was subjected to 100 revolutions. Tablets were dusted using a soft muslin cloth and reweighed. The friability (% F) was then calculated by^16,32.

% Friability (F) = W₀/W×100

Where, W₀ and W are the weight of the tablets before and after the test respectively. The limit for a percentage of friability is between 0.5-1% w/w.

5) Wetting Time:

Five circular tissue papers of 10 cm. diameter are placed in a petri dish with a 10 cm. diameter. 10 ml of water containing amaranth (water soluble dye) is added to the petridish. A tablet is carefully placed on the surface of the tissue paper. The time required for water to reach the upper surface of the tablet is noted as a wetting time^17,28,30

6) Water Absorption Ratio:

A small petri plate with 6 ml of water was filled with a folded piece of tissue paper twice. On the paper, a tablet was placed, and the amount of time needed for full wetness was recorded. A weight was then placed on the moistened pill. The formula below was used to calculate the water absorption ratio, R^16,25.

R = 100(Wa-Wb)/ Wb

Where, Wb - Weight of tablet before absorption

Wa - Weight of tablet after absorption

Three tablets from each formulation were performed

7) In-Vitro Disintegration Time:

The Orodispersible tablet of bilastine gets disintegrated rapidly within 30 seconds. Due to the use of super disintegrants, there is fast disintegration. As a result, patients will get relief from allergies as soon as possible^24,28.

8) Kyoto-Model Disintegration Method/KYO Method:

The ODT samples were categorized according to their water permeability for the Kyoto-model disintegration technique, also known as the KYO method, and the appropriate water volume was chosen. The disintegrative qualities were then assessed using a recently suggested technique using two weights positioned on the tablet's upper surface. Measurement of the disintegrative properties of an ODT sample One piece of filter paper (21 mm in diameter) was placed in a flat-bottomed test tube (22 mm in internal diameter) set at 37°C and an ODT sample was placed in the center of the filter paper. The measuring instrument shown was placed on the upper surface of the tablet. The measuring instrument imposes a double weight on the tablet, a weight in the center of the upper surface of the tablet and on the marginal portion of the upper surface of the tablet, dubbed “inner weight” and “outer weight,” respectively. The completion of disintegration of an ODT sample was defined as the time when the tips of both outer and inner weights made contact with the filter paper. The data are the mean of six determinations³⁴.

9) In-Vitro Dissolution Study:

In vitro dissolution study for an optimized tablet was carried out using the USP paddle method at 50rpm in 900ml of phosphate buffer (pH 6.8) as dissolution media, maintained at 37 ± 0.5°C. 5ml of aliquot was withdrawn at the specified time intervals (1-minute), filtered through Whatman filter paper and assayed spectrophotometrically at 281 nm. An equal volume of fresh medium, pre-warmed at 37°C, was replaced with the dissolution media after each sampling to maintain constant volume throughout the study^22,24.

10) Drug Content:

Ten tablets from each formulation were powdered. The powder equivalent to 20 mg of bilastine was weighed and dissolved in phosphate buffer pH 6.8 in 100 ml. From this suitable dilution was prepared and the solution was analyzed at 281 nm using a UV double beam spectrophotometer (Shimadzu-1800) using pH 6.8 as blank^16,26.

Drug Content (%) = Test Absorbance/Standard Absorbance × 100

Table 3: Evaluation of Precompression Parameters of Bilastine Orodispersible Tablets

Batch	Bulk density (g/ml)	Tapped Density (g/ml)	Carr's Index (%)	Hausner’s Ratio	Angle of Repose (ɵ)
BLS1	0.45±0.025	0.50±0.03	10±1.21	1.1±0.11	30.2±0.50
BLS2	0.42±0.15	0.54±0.03	22.2±.109	1.28±0.13	31.8±0.48
BLS3	0.49±0.05	0.53±0.03	7.5±1.4	1.08±0.14	31.21±1.0
BLS4	0.49±0.05	0.51±0.04	5.88±0.6	1.06±0.29	30.2±0.46
BLS5	0.39±0.07	0.51±0.02	23.5±1.6	1.30±0.13	31±0.46
BLS6	0.32±0.04	0.47±0.06	14.8±0.8	1.17±0.08	31.33±1.05
BLS7	0.32±0.04	0.48±0.05	20.8±1.14	1.2±0.11	30.1±0.61
BLS8	0.38±0.068	0.44±0.04	11.36±0.4	1.1±0.42	30.3±0.24
BLS9	0.41±0.05	0.51±0.07	19.60±0.8	1.2±0.1	31.20±0.5

3. RESULT AND DISCUSSION:

3.1. Pre-formulation Studies:

1. Pre-compression parameter:

Precompression parameter like bulk density, tapped density, Carr’s index, Hausner’s ratio and angle of repose indicates the good flow of the powder blends and the result are given in table 3.

2. Determination of UV Spectrum and Calibration Curve of Bilastine

UV spectrum of bilastine was presented in fig. 1 and the calibration curve shows the straight-line equation given in fig. 2.

Fig. 1: Wavelength Maxima of Bilastine in phosphate buffer pH. 6.8

2. Effect of Independent Variables on Wetting Time:

The wetting time of ODT observed in simulated saliva pH 6.8 was given in table 4.

On applying CCD, it generatesan equation in terms of coded form for wetting time

WT=6.24+4.914+2.369X₂+0.028X₁X₂+0.137X₁²-0.053X₂² - 3

From the results of multiple linear regression analysis, the coefficient X1 bearsa positive sign and X2 bear a negative for the wetting time of the tablet. The addition of more amount of Crospovidone decreased the wetting time while increasing the concentration of MCC PH 102 decreased the wetting time and it was presented in a 3D plot (fig. 8). ANOVA was used to identify the significant effect. The result was found to be significant at that level of probability (p<0.05).

3. Weight Variation Test:

Weight variation test of optimized ODT result present in a range of 187.5±0.74 to 198.65±0.4 mg given in table 5.

Thickness:

The thickness of ODT was determined by using a vernier caliper and the results shown in table 5 given in a range of 4.0±0.05 to 4.3±0.05 mm

4. Hardness Test:

Monsanto hardness tester was used to examine the strength of ODT observed in the range of 1.3±0.1 to 1.7±0.15 Kg/Cm² presented in table 5.

5. Friability:

The friability of the tablets was determined using the Roche friabilator and the result was given in table 5.

6. Water Absorption Ratio:

Orodispersible tablets of water absorption ratio presented in table 5 containing in the range of 70.05 to 97.43.

7. Drug Content:

20 mg powder of bilastine tablet was weighed and dissolved in phosphate buffer pH 6.8 in 100 ml and determined the drug content present in the formulation using a UV spectrophotometer. The result of drug content was given in table 5.

4. CONCLUSION:

The taste of low or moderately bitter bilastine was masked by using the organoleptic method and novel anti-histamine Orodispersible tablets (ODTs) of bilastine were prepared by direct compression method. Nine formulations (BLS1-BLS9) were prepared by varying super disintegrant concentrations to optimize the best formulation by 3²factorial designs and a central composite design in the quadratic model was utilized by design expert software (version13.0.5.0). Also improved the disintegration and dissolution rate within a time limit and prepared ODT shows the best results as compared with the marketed brand of an uncoated tablet of bilastine. An in-vitro drug release study was carried out and based on the result BLS8 optimized batch identified the best formulation among all the batches. The in-vitro drug release was more than 100% within 10 minutes. Also compared with the marketed uncoated tablet of bilastine the prepared ODT shows the best results.

Also, conclude that the Kyoto model disintegration method (KYO method) can evaluate the disintegration time of ODT formulation in the development stages and during quality control.

So, it represents that the use of super disintegrants increases the release of the drug Bilastine. There it may be concluded that an Orodispersible tablet was a suitable drug delivery system for Bilastine.

Thus, the Orodispersible tablet was successfully prepared for a patient who is suffering from difficulty swallowing or dysphagia, patients mainly for pediatric above the age of 12 years, geriatrics, or patient who have no access to water, and also provides faster and better drug release thereby, improving the bioavailability of drug as compared to the conventional marketed formulation.

5. REFERENCES:

1. T.Y. Puttewar. M.D. Kshirsagar. A.V. Chandewa. R.V. Chikhale; Formulation and evaluation of Orodispersible tablet of taste masked doxylamine succinate using ion exchange resin. Journal of King Saud University (Science). 2010; 22: 229–240.

2. Kandukuri Rekha. R. Aruna. Dr. Rinku Mathappan. Dr. Mekkanti Manasa Rekha. S. Karthik. Formulation and Development of Bilastine Tablet; World Journal of Pharmaceutical Research. 2019; Volume 8. Issue 7: 2197-2224.

3. Harmik Sohi. Yasmin Sultana. and Roop K. Khar; Taste Masking Technologies in Oral Pharmaceuticals: Recent Developments and Approaches. Drug Development and Industrial Pharmacy; 2004; Vol. 30. No. 5: pp. 429–448.

4. Tanaji D. Nandgude. Vivekanand Kisan Chatap. Kiran Bhise. DK Sharma. Mouth dissolving tablets: Geriatrics and paediatrics friendly drug delivery system. Indian Drugs. 2007; 440 - 471.

5. Dali Shukla. Subhashis Chakraborty. Sanjay Singh. Brahmeshwar Mishra. Mouth Dissolving Tablets I: An Overview of Formulation Technology. Scientia Pharmaceutical. 2009; 77: 309–326.

6. Ruchika Sharma. M. S. Ashawat. C. P. S Verma. Neha Kumari. A Fast Release Tablet Containing Herbal Extracts (Ginger, Cinnamon, Termermeric, Long Pepper and Punarnava). Asian J. Pharm. Tech. 2020; 10(4): 231-240.

7. Sarfaraz RM. Ahmad M. Mahmood. Khan Hu. Sher M. Maheen. Bashir. Iqbal A. and. Ashan H. Formulation and In-Vitro Evaluation of Novel Atorvastatin Amlodipine Orodispersible Tablet; International Journal of Biology Pharmacy and Allied Sciences. 2014; 3(6): 941-951.

8. Ulrike Stange. Christian Fuhrling. Henning Gieseler; Formulation. Preparation. and Evaluation of Novel Orally Disintegrating Tablets Containing Taste-Masked Naproxen Sodium Granules and Naratriptan Hydrochloride; Pharmaceutics Drug Delivery and Pharmaceutical Technology. 2014; 103:1233–1245.

9. Oral Disintegrating Tablets: Background and Review on Recent Advancement. by Nehaben Gujarati. Advance Pharmaceutical Journal. 2017; 2(2): 56-64.

10. Ramakant Joshi. Navneet Garud and Wasim Akram. Fast Dissolving Tablet: A Review. International Journal of Pharmaceutical Sciences and Research. 2020; Vol. 11(4): 1562-1570.

11. Muthukumar. SundaraGanapathy. Design and Evaluation of Hydralazine Hydrochloride Mouth Dissolving Tablet for The Management of Hypertension. International Journal of Recent Scientific Research Research. 2017; Vol. 8. Issue. 5: pp. 17230-17235.

12. Abhishek S. Pujari. Nitin A. Gaikwad. Indrajeet V. Mane. Ganesh B. Vambhurkar. Pravin P. Honmane. In-Vitro Evaluation of Different Marketed Brands of Paracetamol Tablets using Quality Control Tests. Asian J. Pharm. Tech. 2018; 8(3): 119-122.

13. K. Sampath Kumar. D. Maheswara Reddy. Y. Dastagiri Reddy. J. Balanarasimha Goud and Abdul Basit. Development and Evaluation of Mouth Dissolving Tablets of Montelukast Sodium Using Co-processed Excipients. Journal of Pharmaceutical Research International 2021; 33(14): 21-29.

14. Durgaramani Sivadasan. Muhammad Hadi Sultan. Osama Madkhali. Shamama Javed. Aamena Jabeen. Formulation and in-Vitro Evaluation of Orodispersible Tablets of Fexofenadine Hydrochloride. Tropical Journal of Pharmaceutical Research. 2020; 19 (5): 919-925.

15. M. Aruna. Samreen Sultana. Shaik Harun Rasheed. Formulation and Evaluation of Fast Disintegrating Tablets of Metoprolol Succinate Using Various Superdisintegrants. International Journal of Research in Pharmaceutical Sciences and Technology. 2019; 1(2): 79-83.

16. Meghawati R. Badwar. Sandhya L. Borse. Manish S. Junagade. Anil G. Jadhav. Formulation and Evaluation of Mouth Dissolving Tablet of Amlodipine Besylate. International Journal of Applied Pharmaceutics. 2019; Vol 11. Issue 4: 132-139.

17. Nirmala Rangu. B. Chaitanya Kumari. Ganesh Akula. A Jaswanth. Formulation and Evaluation of Oro Dispersible Tablets of Atenolol by Sublimation Method. Asian J. Pharm. Tech. 2018; 8(1): 01-07.

18. Swati L. Khedekar. Subhash V. Deshmane. Formulation. Development and Evaluation of Mouth Dissolving Tablet Containing Cyclodextrin as Taste Masker. Journal of Pharmacy. 2019; Volume 9. Issue 1: 21-29.

19. Rupali Rana. Nisha Devi. Vishal Kumar. Reena Thakur. Shivali Single. Sachin Goyal. The Formulation and Evaluation of Mouth Dissolving Tablet Levocetirizine by using synthetic super disintegrants. Himalaya Journal of Health Sciences. 2020; 5(1): 1-11.

20. Savithri T. B. Farooq. C. Rashmi. Research Article on Formulation and Evaluation of Fast Dissolving Tablets of Canagliflozin by Direct Compression Method. European Journal of Biomedical and Pharmaceutical Sciences. 2020; Volume 7. Issue 1: 374-379.

21. Dillip Kumar Brahma. Dr. Neeraj Sharma. Design and Evaluation of Fast Dissolving Tablet by Using Novel Technique for Effective Treatment of Diabetes. Journal of Critical Review. 2020; Volume 7. Issue 05: 2136-2142.

22. Anju Govind. Manjunath B. Menden. Ravikumar. Simila. Mercy. Narayana Swamy V. B. Formulation and Evaluation of Mouth Dissolving Tablets of Deflazacort. Asian J. Pharm. Tech. 2016; 6(2): 91-98.

23. Vani H. Bhargava. Poonam S. Sable. Deepak A. Kulkarni. Geeta P. Darekar. Formulation and Evaluation of Mouth Dissolving Tablet of Benazepril Hydrochloride. Research Journal Pharm. and Tech. 2021; 14(6): 3161-3166.

24. Rajendra Singh. Swati Saxena. Sarang Jain. Formulation and Evaluation of Mouth Dissolving Tablet Containing Nonsteroidal Anti-inflammatory Drug. Research Journal Pharm. and Tech. 2021; 14(1): 432-436.

25. Venkatalakshmi Ranganathan. Jason Yoong. Development and Evaluation of Mouth Dissolving Tablets Using Natural Super Disintegrants. Journal of Young Pharmacists. 2017; Vol 9. Issue 3: 332-335.

26. Neha Srivastava. Seema Thakur. Anchal Bajaj. Nikita Sahi. Fast Dissolving Tablets: A novel approach in the Delivery System. Asian J. Pharm. Tech. 2016; 6 (3): 148-154.

27. Praveen N. Ramesh Y. Gnanaprakash K. Gobinath M. Mahesh N. Monica A. Formulation and Evaluation of Levamisole Oral Dispersible Tablets. International Journal of Research in Pharmaceutical Sciences. 2015; 6(3): 256-261.

28. Sudarshan Singh. S.S. Shyaleand P. Karade. Formulation and Evaluation of Orally Disintegrating Tablets of Lamotrigine. International Journal Pharmaceutical Sciences and Nanotechnology. 2015; Vol 8. Issue 2: 2881-2888.

29. Ashish Masih. Amar Kumar. Shivam Singh. Ajay Kumar Tiwari. Fast Dissolving Tablets: A Review. International Journal of Current Pharmaceutical Research. 2017; Vol 9. Issue 2: 8-18.

30. Rohan Patil. Neha Patil. Aniket Patil. S. J. Shid. V.N. Dange. C.S. Magdum. S.K. Mohite. Preparation and Evaluation of Fast Dissolving Tablet Tramadol Hydrochloride. Asian J. Pharm. Tech. 2016; 6 (3): 183-185.

31. Abay FB and Ugurlu T. Orally Disintegrating Tablets: A Short Review. Journal of Pharmaceutics & Drug Development. Volume 3. Issue 3. 2015; 1-8.

32. Sagar T. Malsane. Smita S. Aher. R B Saudagar. A Review on Fast Dissolving Tablet. International Journal of Current Pharmaceutical Review and Research. 2017; 8(3): 284-292.

33. Nikita K.Patel. Sahilhusen. Mukesh S. Patel. A Review on Orodispersible Tablets-As a Novel Formulation for Oral Drug Delivery Systems. Journal of Pharmaceutical Sciences and Bio scientific Research. Volume2015. 5. Issue 3. 286-294.

34. Ryo Kakutani. Hiroyuki Muro. Tadashi Makino. Development of a New Disintegration Method for Orally Disintegrating Tablets. Chem.Pharma Bull. (2010); 58(7): 885-890.

35. Dev Asish. Yadav Shravan Kumar. Kar S.K. Mohanty Smitapadma. Shelke Om. Formulation and Characterization of Aceclofenac Mouth Dissolving Tablet by QbD. Journal of Drug Delivery & Therapeutics. 9(5). 2019; 9(5): 43-50.

36. Rebecca. Ravi Kumar. Narayana Swamy V. B. Formulation and In-Vitro Evaluation of Mouth Dissolving Tablets of Labetalol HCl by Sublimation Method. Asian J. Pharm. Tech. 2016; 6 (2): 70-80.

37. Jain N. K. 'Pharmaceutical Product Development. CBS Publishers and Distributors Pvt. Ltd. Second Edition: 369-394.

38. Jelena Djuris. Computer-Aided Applications in Pharmaceutical Technology. Published by Woodhead Publishing Limited. 2013; 1-11.

Received on 09.09.2022 Modified on 24.12.2022

Asian J. Pharm. Tech. 2023; 13(3):157-165.

DOI: 10.52711/2231-5713.2023.00028

Batches	Variable Level in Coded Form		Dependent variables (Y)
Batches	X1	X2	% Drug Release (%)	Disintegration Time (Sec)	Wetting Time (Sec)
BLS1	0	1	95.61	20.15	30.41
BLS2	-1	0	96.78	20.3	20.08
BLS3	1	1	95.88	19.54	3.46
BLS4	1	0	101.6	19.26	8.5
BLS5	0	-1	102.4	20.18	28.09
BLS6	1	-1	93.12	20.11	29
BLS7	0	0	97.81	20.18	8.72
BLS8	-1	1	102	18.57	18.61
BLS9	-1	-1	107.1	19.69	14.3

Batch	Weight Variation (mg)	Thickness (mm)	Diameter	Hardness (Kg/Cm²)	Friability (%)	Water Absorption Ratio	Drug Content (%)
BLS1	187.5±0.74	4.0±0.05	8.0± 0.05	1.5±0.15	0.41±0.07	71.50	98.81
BLS2	197.5±0.63	4.0±0.1	8.0±0.05	1.5±0.1	0.5±0.05	70.05	100.71
BLS3	186.8±0.75	8.0±0.05	8.0±0.05	1.5±0.15	0.6±0.06	74.47	99.36
BLS4	198.1±0.75	4.0±0.11	8.0±0.05	1.3±0.1	0.41±0.07	97.43	101.89
BLS5	198.05±0.97	4.0±0.05	8.0±0.05	1.6±0.1	0.41±0.07	86.66	100.27
BLS6	198.45±0.47	4.1±0.05	8.0±0.11	1.3±0.1	0.4±0.08	94.35	97.21
BLS7	198.5±0.77	4.2±0.1	8.0±0.11	1.5±0.1	0.5±0.05	98.46	96.53
BLS8	198.65±0.4	4.1±0.1	8.0±0.1	1.7±0.15	0.6±0.05	84.92	99.39
BLS9	198.55±0.2	4.3±0.05	8.0±0.1	1.5±0.1	0.5±0.04	95.47	93.61