INTRODUCTION:

Arthritis is an inflammation of one or more joints, resulting in stiffness and discomfort that can get worse with age. There are as many as 100 types of arthritis with distinctive symptoms and causes^1,4. Osteoarthritis is a generative disease of synovial joints characterized by focal loss of articular hyaline cartilage with the proliferation of new bones and remodeling of joint contour^5-9. For quite a while, NSAIDs have been a key component of the treatment for OA symptoms.

The mechanism by which NSAIDs exert their anti-inflammatory and analgesic effects is via inhibition of the prostaglandin-generating enzyme, cyclo-oxygenase (COX)^10-14. For the pain and inflammation associated with OA, these particular COX-2 inhibitors work wel1^15-17. This pharmacologic activity gives celecoxib its analgesic, anti-inflammatory, and antipyretic effects^18-19.

A sustained release dosage form is a dosage form that maintains the therapeutic blood or tissue levels of the drug by continuous release of medication for a prolonged time^20-22.Sustained release formulations are used for special effects, e.g., Treatment of Arthritis. It reduces side effects. Sustained release formulations give maximum bioavailability with a minimum dose and improve patient compliance. These are self-medicated formulations that’s why it reduces nursing and hospitalizing time. There is an exaggerated release of drugs i.e., dose dumping. Sustained-release formulations have higher manufacturing costs^23-25.

MATERIAL AND METHOD:

Materials:

Celecoxib was obtained as a gift sample from Hetero Labs Limited, Baddi (Himachal Pradesh) India. HPMC K100, Micro-crystalline cellulose, PVP K30 was procured from Loba Chemie Pvt. Ltd., Mumbai.

Methods:

Preformulation Studies:

The drug Celecoxib was characterized by its identity and purity. The following studies were performed^26,27.

Determination of Absorption Maxima of Celecoxib:

A solution of Celecoxib containing the concentration 10 μg/ ml was prepared in 0.1N HCl and phosphate buffer 6.8 pH respectively, and UV spectrum was taken using a UV spectrophotometer. The solution was scanned in the range of 200 – 400nm^28,29.

Drug and Excipient Compatibility Studies:

Compatibility of the Celecoxib with HPMC K 100 and PVP K30 used to formulate bilayer tablets was established by FTIR spectral analysis and Differential Scanning Calorimetry ^30-32.

Factorial design:

A 2³full factorial design by Design Expert software (Design Expert Software Version 11.1.0.1) was used for the development of a sustained-release tablet. Dependent factors are % drug release, and wetting time and independent factors are MCC, HPMCK100, AND PVP K30.³³

Table 1. Experimental design as per 2³ factorial designs for Sustained Release Bilayer Tablet

Batch code	Levels of independent variables (factors) employed
Batch code	MCC (X1)	HPMC K100 (X2)	PVP K30 (X3)
1	65	100	20
2	65	50	30
3	95	75	25
4	125	100	20
5	65	50	20
6	125	50	20
7	65	100	30
8	125	50	30
9	125	100	30

EXPERIMENTAL METHODS:

Formulation of Immediate Release layer:

The immediate release tablet was prepared by blending Celecoxib uniformly with different types of super disintegrants (Sodium Starch Glycolate, Cross povidone, and Croscarmellose sodium) as per the formulae given in Table no 3. The drug-super disintegrant blend was then mixed with MCC using morter and pestle for 10 min. The final mass was lubricated with 0.5%w/w magnesium stearate and 0.5%w/w talc and compressed using a tablet compression machine using 3 BB punches³⁴.

Table 2. Compositions of Immediate Release Tablets (100 mg)

Sr.No.	Ingredients	F₁	F₂	F₃	F₄	F₅	F₆	F₇	F₈	F₉
Sr.No.	Ingredients	(Weight in mg)
1.	Celecoxib	54	54	54	54	54	54	54	54	54
2.	Chitosan (%)	1	2	3	4	5	6	7	8	0
3.	MCC	18	13	08	18	13	08	18	13	08
4.	Sodium starch glycolate	5	10	15	-	-	-	-	-	-
5.	Croscarmellose sodium	-	-	-	5	10	15	-	-	-
6.	Cross Povidone	-	-	-	-	-	-	5	10	15
7.	Magnesium stearate	1	1	1	1	1	1	1	1	1
8.	Talc	2	2	2	2	2	2	2	2	2

Table 3. Compositions of sustained release tablets

Sr. No.	Ingredients	F1	F2	F3	F4	F5	F6	F7	F8	F9
Sr. No.	Ingredients	(Weight in mg)
1.	Celecoxib	145	145	145	145	145	145	145	145	145
2.	MCC	65	65	95	125	65	125	65	125	125
3.	HPMC K100M	100	50	75	100	50	50	100	50	100
4.	PVPK-30	20	30	25	20	20	20	30	30	30
5.	Lactose	5	10	25	15	10	15	10	5	15
6.	Magnesium stearate	2	2	2	2	2	2	2	2	2
7.	Talc	3	3	3	3	3	3	3	3	3
8.	Isopropyl alcohol	10	10	10	10	10	10	10	10	10

Formulation of sustained release layer:

The sustained release layer of the tablet was prepared by wet granulation technique by mixing Celecoxib uniformly with different proportions of HPMC K 100M, Micro-crystalline cellulose. Polyvinyl pyrolidone K30 (3%w/v in IPA) was used as a binder. In order to obtain granules, the wet bulk was processed through 30 sieve. The granules were dried at 50◦ in a hot air oven. The granules of 30/60# size was lubricated with 1% w/w magnesium stearate^35,36

Compression of Bilayer Tablet:

The bilayer tablet of celecoxib was prepared using a tablet compression machine equipped with 11 mm round punches. The dies were initially filled with the weighed amount immediate release portion and were lightly compressed. Over this compressed layer, the required quantity of the sustained release layer granules was placed and compressed to obtain the hardness of the tablet 5–6 kg/cm². It was observed that the table compressed at this force did not show any layer separation. The total weight of the tablet was kept constant, i.e., 500mg for all formulations³⁷.

EVALUATION PARAMETERS:

Pre-compression studies:

Angle of repose:

funnel was fixed at a height of 2 cm over the platform. About 20 g of sample was slowly passed along the wall of the funnel till the tip of the pile formed touches the stem of the funnel. A rough circle was drawn around the pile base and the radius of the powder cone was measured

θ = tan-1 (h/r)

Where, θ = angle of repose, h = height of powder cone, r = radius of the powder cone

Bulk density and Tapped density:

Bulk density is outlined as the magnitude relation of mass of powder by bulk volume.

Bulk density (g/ml) = weight of sample/bulk volume

Tapped density:

After mechanical tapping in measuring cylinder, there will be an associate degree of increase within the bulk density which is called as tapped density. Tapped density = Weight of powder taken/Tapped Volume

Compressibility index:

The characteristics of the powder to be compressed is measured by the compressibility index and it conjointly helps in the measurement of interaction between the particles and settling property of powder particles.

% Carr’s Index = Tapped density − Bulk density/tapped density x 100

Hausner’s ratio:

It provides an indication of the degree of densification, which could result from the vibration of the feed hopper^38-40.

Hausner’s Ratio = Tapped density /Bulk density

Post compression parameter:

Weight variation:

Twenty tablets were selected randomly from each formulation batch and weighed individually. The average weight and % weight variation was calculated.

Hardness:

A Monsanto hardness tester was used to measure the hardness of tablets. Tablets were placed between two anvils, and forced to the anvils, and the crushing strength that caused the tablets to break was recorded.

Thickness:

The thickness of the tablets was determined by the Digital Vernier Caliper instrument. Ten tablets were used for the determination of thickness from each batch.

Friability:

The friability (%) of tablets was determined by using a Roche type of friability testing apparatus. Twenty tablets were weighed and placed in the Roche friability test apparatus at 25rpm. After 100 revolutions, the tablets were dedusted and weighed again. The friability was determined as the percent loss in weight of the tablets

% Weight loss = W1 − W2/W1 x 100

Where, W1 = initial weight, W2 = final weight

Disintegration test:

Six tablets were selected randomly from each batch for the disintegration test. The disintegration test was performed by using Electro lab disintegration tester. Disintegration time (DT) was measured for all tablets⁴¹.

Drug content:

10 tablets of each formulation were weighed and powdered. The equivalent weight of powder was taken and dissolved in pH 6.8 buffer and make up a volume of up to 100 ml. Further 1mL of the above solution was diluted to 10 ml with pH 6.8 buffer. UV absorbance was measured at 252 nm⁴².

In-vitro drug release study:

In-vitro release studies were carried out USP II paddle-type dissolution test apparatus. An in-vitro drug release study was performed on 3 tablets of each batch⁴³.

Wetting time:

Taking five circular tissue papers of 10 cm diameter and place in a petridish of 10 cm diameter. Ten milliliters of water soluble dye solution is added to the petridish and the tablet is placed on the surface of tissue paper. The time required for water to reach the upper surface of the tablet is noted as wetting time⁴⁴.

Stability study:

The optimized batch was kept in an environmental stability chamber for accelerated stability conditions at 40°C ± 2°C temperature and 75 ± 5 % relative humidity for a period of 1 months. The samples were withdrawn at 0 and 1 intervals and evaluated for physical parameters, drug content, and in-vitro drug release⁴⁵.

RESULTS AND DISCUSSIONS:

Determination of Absorption Maxima of Celecoxib:

The absorbance maximum of Celecoxib was found to be at 250 nm and 252 nm in 0.1 N HCl and 6.8 pH phosphate buffer respectively.

Fourier Transform Infrared Spectra:

The FTIR spectrum of Celecoxib was recorded. the values of peaks were confirmed with the reported peaks and it was in accordance with its chemical structure.(Figure-1).

Differential Scanning Calorimetry:

The thermogram of Celecoxib showed an endothermic peak at 161.62°C with an end set at 164.31°C, which indicates the amorphous nature of the drug. DSC thermogram is shown in Figure 2. A. It was concluded that the procured sample confirms the test for Celecoxib for purity and quality. There was no considerable change in DSC endothermic values when comparing the pure drug with the excipients shown in Fig 2. B.

Post Compression Parameters:

Post compression parameters of Celecoxib Bilayer Tablets:

The weight variation of all factorial batches was less than 7.5%. The thickness of tablets of factorial batches was 4.42 to 4.64 mm. The friability of tablets was less than 0.5%, which indicates good handling and transportation characteristics. The hardness of Celecoxib double-layered tablets was 5 Kg/cm². The tablets were assayed and the drug content was found to be in the range of 85.29 - 98.25.

1. A spectrum of Celecoxib

1. B celecoxib–excipient compatibility

Figure 1. I.R. spectrum

2.A DSC thermogram of Celecoxib pure drug

2.B thermogram of Celecoxib and excipients

Figure 2. DSC

Table 4. Post-compression Parameters of Celecoxib Bilayer Tablets

Batch	Weight Variation (mg)	Hardness (Kg/cm²)	Thickness (mm)	Friability (%)	Drug Content (%)	Wetting time (sec)
L1	408.6±1.91	5	4.47±0.023	0.26±0.033	91.08±1.56	60±0.47
L2	401.2±1.44	5	4.64±0.047	0.35±0.015	90.10±1.64	53.21±0.49
L3	409.6±1.26	5	4.46±0.023	0.41±0.044	88.85±1.46	53±0.12
L4	410.5±1.91	5	4.57±0.047	0.41±0.075	98.25±1.19	51.12±0.25
L5	409.6±1.71	5	4.54±0.029	0.39±0.029	94.65±1.42	55.23±0.30
L6	408.9±1.98	5	4.42±0.020	0.36±0.032	90.29±1.92	49.1±0.20
L7	404.1±1.48	5	4.44±0.035	0.24±0.055	90.89±1.83	49±0.54
L8	402.3±1.33	5	4.64±0.042	0.41±0.078	88.96±1.77	42.3±0.31
L9	411.9±1.71	5	4.45±0.028	0.44±0.061	85.29±1.86	48.12±0.61

(mean± SD, n=3)

Table 5. In-vitro drug release of bilayer tablet

Time (Hrs)

L1(%)

L2(%)

L3(%)

L4(%)

L5(%)

L6(%)

L7(%)

L8(%)

L9(%)

0.1 N HCl

45.03

±0.40

44.1

±0.41

55.68

±0.40

39.93

±0.67

56.7

±0.65

43.76

±0.66

44.77

±0.22

45.45

±0.22

34.65

±0.23

Phosphate buffer (pH 7.4)

12.39

±1.51

18.20

±1.46

27.30

±1.64

12.93

±0.78

13.07

±0.64

12.34

±0.69

12.39

±1.16

13.97

±1.02

14.19

±0.99

21.01

±1.29

29.77

±1.16

37.92

±1.06

31.79

±1.50

27.09

±1.12

32.21

±0.99

21.01

±0.79

32.27

±0.71

24.17

±0.62

37.21

±1.92

35.11

±1.43

47.69

±1.44

36.80

±1.86

37.25

±1.77

40.15

±1.06

37.21

±1.39

38.41

±1.21

38.25

±0.86

57.56

±0.86

51.16

±0.77

66.29

±1.43

46.34

±1.80

50.84

±1.79

50.72

±1.56

46.31

±0.58

48.41

±0.55

49.82

±0.41

72.38

±1.82

66.18

±0.98

72.27

±0.87

61.11

±1.03

72.38

±0.89

65.96

±1.78

61.07

±1.83

64.09

±1.61

63.37

±0.83

80.54

±1.64

78.81

±1.88

79.76

±0.91

69.20

±1.83

80.54

±1.16

78.24

±1.00

69.17

±1.54

75.69

±1.38

76.77

±0.76

90.10

±0.81

85.09

±0.95

82.82

±0.56

86.01

±0.11

96.50

±0.32

91.20

±0.45

85.30

±0.45

83.0

±0.42

82.00

±0.70

In-vitro Drug Release Study of Celecoxib Bilayer Tablets

(mean± SD, n=3)

Fig 3: Comparative study of drug release vs. time of all batches

The batch L5 gives sustained release of the drug for 24 hours.

Table 6. Formulation suggested by 2³ Factorial design with their response

Std	Run	Factor 1 A: MCC mg	Factor 2 A: HPMC K100 mg	Factor 3 A: PVP K30 mg	Response 1 Drug release %	Response 2 Wetting time sec
3	1	65	100	20	90	60
5	2	65	50	30	85	53.21
9	3	95	75	25	82.2	53
4	4	125	100	20	86	51.12
1	5	65	50	20	96.5	55.23
2	6	125	50	20	91.2	49.1
7	7	65	100	30	85.3	49
6	8	125	50	30	83	42.3
8	9	125	100	30	82	48.12

Ex-vivo permeation study:

F9 (tablet with no chitosan) gave 62.8 % permeation and F5 (tablet with 5% w/w chitosan) gave 81.15 % permeation which shows chitosan can increase drug permeability by acting as a permeation enhancer

Fig 6: Comparative study of drug permeation of F5 and F9

Stability study:

Stability testing on optimized batches of bilayer tablets as per ICH guidelines (Q1A R2) was carried out. After checking the physical parameters, no significant change was found in all the batches before and after the stability study. The results obtained as shown in the table below.

Table 8. Evaluation parameters of stability batch H5

Evaluation parameters	Before stability Storage	After 1 month storage
Hardness (kg/cm2)	5	5
Friability (%)	0.39 ± 0.015	0.39 ±0.021
Weight variation (mg)	409.6 ± 1.56	409.6 ±1.48
Drug content (%)	98.65 ± 0.36	97.99 ±0.26
% Drug release	96.50 ± 0.43	95.05 ±0.86
Wetting time (sec)	55 ±0.30	55 ±0.23

(mean± SD, n=3)

CONCLUSION:

Immediate release tablets of Celecoxib were prepared by using varying concentrations of super-disintegrants. Hence, the H6 batch is considered an optimized batch. The immediate release layer also contains various concentrations of Chitosan. Bilayer tablets quickly release the immediate release layer get released within 60 min, subsequently from the sustained release layer the Celecoxib is released in a sustained manner, which would be required to maintain plasma drug concentration for effective treatment for a longer duration of time. Therefore, it was concluded that the developed formulation may be suitable for the effective treatment of Osteoarthritis in patients.

ACKNOWLEDGMENTS:

The author is thankful to Hetero Labs Limited, Baddi, Himachal Pradesh for Supplying a gift sample of Celecoxib. Also thankful to the principal and management of Kamla Nehru College of Pharmacy, Butibori, Nagpur for providing a research facility.

REFERENCES:

1. Tanaji D. Nandgude, Priyajit S. Hasabe, Anuja K. Kolsure. Clinical Features and Treatment of Rheumatoid Arthritis: A Review. Research J. Pharm. and Tech. 2018; 11(12): 5701-5706. doi: 10.5958/0974-360X.2018.01032.6 https://doi.org/10.5958/0974-360X.2018.01032.6

2. Mandl LA. Osteoarthritis year in review 2018: clinical. Osteoarthritis and cartilage. 2019; Mar 1; 27(3): 359-364. https://doi.org/10.1016/j.joca.2018.11.001

3. Kloppenburg M, Berenbaum F. Osteoarthritis year in review 2019: epidemiology and therapy. Osteoarthritis and cartilage. 2020; Mar 1; 28(3): 242-248. https://doi.org/10.1016/j.joca.2020.01.002

4. Pagar KR, Khandbahale SV, Kasar PM. Osteoarthritis: Pathophysiology and current treatment modalities. Asian Journal of Pharmaceutical Research. 2019; Oct; 9(4): 289-298.

5. Cooper C, Chapurlat R, Al-Daghri N, Herrero-Beaumont G, Bruyère O, Rannou F, Roth R, Uebelhart D, Reginster JY. Safety of oral non-selective non-steroidal anti-inflammatory drugs in osteoarthritis: what does the literature say?. Drugs and aging. 2019; Apr 1; 36(Suppl 1): 15-24 https://doi.org/10.1007/s40266-019-00660-1

6. Malfait, A.M. and Schnitzer, T.J. Towards a mechanism-based approach to pain management in osteoarthritis. Nature Reviews Rheumatology. 2013; 9(11): 654-664. https://doi.org/10.1038/nrrheum.2013.138

7. Chaudhary A, Pandit V, Ashawat MS, Kumar T. Rheumatoid arthritis, a laconic review to understand their basic concept and management process. Asian Journal of Pharmaceutical Research. 2022; 12(4): 312-22. http://dx.doi.org/10.52711/2231-5691.2022.00051

8. Mourya H, Chauhan R, Joshi R, Akram W, Garud N. Bilayer tablets: A promising novel drug delivery system. Research Journal of Pharmacy and Technology. 2023; 16(5): 2517-21. http://dx.doi.org/10.52711/0974-360X.2023.00414

9. George N, Pillai MK, Haribabu Y. Bilayer floating tablets: An updated review. Research Journal of Pharmacy and Technology. 2022; Mar 1; 15(3): 1337-42. DOI: 10.52711/0974-360X.2022.00223

10. Liu L, Xu X. Preparation of bilayer-core osmotic pump tablet by coating the indented core tablet. International journal of pharmaceutics. 2008; Mar 20; 352(1-2): 225-30. https://doi.org/10.1016/j.ijpharm.2007.10.047

11. Akhtar M, Jamshaid M, Zaman M, Mirza AZ. Bilayer tablets: A developing novel drug delivery system. Journal of Drug Delivery Science and Technology. 2020; Dec 1; 60: 102079. https://doi.org/10.1016/j.jddst.2020.102079

12. Deshpande RD, Gowda DV, Mahammed N, Maramwar DN. Bi-layer tablets-An emerging trend: a review. International Journal of Pharmaceutical Sciences and Research. 2011; Oct 1; 2(10): 2534.

13. Li SP, Karth MG, Feld KM, Di Paolo LC, Pendharkar CM, Williams RO. Evaluation of bilayer tablet machines—a case study. Drug Development and Industrial Pharmacy. 1995; Jan 1; 21(5): 571-590. https://doi.org/10.3109/03639049509048124

14. Chauhan M, Suthar S, Shah A, Polara M, Patel M, Patel J. Bilayer tablet: Immediate release and sustain release: A review. Research Journal of Pharmacy and Technology. 2012; 5(6): 716-720

15. Kaur Bhatia J, Kaur R, Singh S. Formulation and optimization of hydrochlorothiazide mouth dissolving tablets by using co-processed superdisintegrants. Int J Pharm Sci Rev Res. 2013; 21(2): 46-51.

16. Purushothaman P, Sha A, Vetrichelvan T. Formulation development and Evaluation of immediate and sustained release Bilayer Tablets Containing Amitriptyline HCl and Pregabalin for the treatment of Neuropathic Pain. Asian Journal of Pharmacy and Technology. 2017; 7(3): 127-36.

17. Pandey P, Dahiya M. Oral disintegrating tablets: a review. International Journal of Pharma Research and Review. 2016; Jan; 5(1): 50-62.

18. Mayuri B. Patil, Priyanka M. Salve, Shital V. Sonawane, Avish D. Maru, Jayshree S. Bhadane, Rajendra K. Surawase. Technologies in Bilayer Tablet Manufacturing: A Review. Research Journal of Pharmaceutical Dosage Forms and Technology. 2021; 13(3):253-258. doi: 10.52711/0975-4377.2021.00042

19. Kumar PA, Surendrabhoopathi G, Kulakarni SV. Current Innovation in Layered Tablet Technology. Asian Journal of Research in Pharmaceutical Science. 2013; 3(4): 189-94. DOI: 10.52711/2231-5659

20. Ratnaparkhi MP, Gupta Jyoti P. Sustained release oral drug delivery system-an overview. Terminology. 2013; 3(4): 10-22270.

21. Gupta, M.M. and Brijesh, R. A review on: sustained release technology. International Journal of Therapeutic Application. 2012; 8(1):1-23.

22. Chauhan M, Suthar S, Shah A, Polara M, Patel M, Patel J. Bilayer tablet: Immediate release and sustain release: A review. Research Journal of Pharmacy and Technology. 2012; 5(6): 716-20.

23. Venkat Thota. Sustained release oral drug delivery system-an overview. International Journal of Pharma Research. 2015; 2(3): 11-21.

24. Garna, S., Chaturvedi, S., Agrawal, V. and Alim, M. Formulation approaches for sustained release dosage forms: a review. Asian J Pharm Clin Res. 2015; 8(5): 46-53.

25. Shukla S, Pandya V, Bhardia P, Jonwal N, Bhatt D. Bi-layer Tablet system–An Innovative trend. Asian Journal of Pharmaceutical Research. 2013; 3(2): 49-56.

26. Stieger N, Liebenberg W, Wessels JC. UV spectrophotometric method for the identification and solubility determination of nevirapine. Die Pharmazie. 2009; Oct 1; 64(10): 690-691. Die Pharmazie, 01 Oct 2009, 64(10):690-691

27. Thimmasetty J, Subrahmanyam CV, Vishwanath BA, Babu PR. Solubility parameter estimation of celecoxib by current methods. Asian Journal of Research in Chemistry. 2009; 2(2): 188-195.

28. Karajgi SR, Metri S, Tiwari V, Hulyalkar S, Rub TA, Patil AS. UV spectrophotometric method for the quantitative estimation of celecoxib in capsule dosage forms. Der Pharmacia Lettre. 2016; 8(10): 247-257.

29. Kumar P, Chaudhary M, Bhattacharya S, Juyal V. Validated Analytical Method Development of Celecoxib in Bulk, Tablet and Rat Plasma by UV-Spectroscopy. Research Journal of Pharmacy and Technology. 2010; 3(3): 894-6.

30. Primo FT, Fröhlich PE. Celecoxib identification methods. Acta Farmaceutica Bonaerense. 2005;24(3):421.

31. Bunaciu AA, Aboul-Enein HY, Fleschin S. Application of Fourier transform infrared spectrophotometry in pharmaceutical drugs analysis. Applied Spectroscopy Reviews. 2010; May 17; 45(3): 206-219. https://doi.org/10.1080/00387011003601044

32. Ford JL, Timmins P. Pharmaceutical thermal analysis: techniques and applications. 1989 Jan. https://lccn.loc.gov/88037189

33. Momin MM, Kane S, Abhang P. Formulation and evaluation of bilayer tablet for bimodal release of venlafaxine hydrochloride. Frontiers in pharmacology. 2015; Jul 9; 6: 144. https://doi.org/10.3389/fphar.2015.00144

34. Jadhav SB, Mali AD, Rajeghadage SH, Bathe RS. Formulation and evaluation of immediate release tablets of Imipramine hydrochloride. Int. J. Biomed. Adv. Res. 2014; 5(11):559-565. DOI:10.7439/ijbar

35. Shanmugam S, Chakrahari R, Sundaramoorthy K, Ayyappan T, Vetrichelvan T. Formulation and evaluation of sustained release matrix tablets of Losartan potassium. Int J Pharm Tech Res. 2011; Jan; 3(1): 526-534.

36. Lachman L, Lieberman HA, Kanig JL. The theory and practice of industrial pharmacy. Philadelphia: Lea and Febiger; 1976.

37. Nilawar PS, Wankhade V, Badnag D. An emerging trend on bilayer tablets. Int J Pharm Pharm Sci Res. 2013; 3(1): 15-21.

38. Nyol S, Gupta MM. Immediate drug release dosage form: a review. Journal of Drug Delivery and Therapeutics. 2013; Mar 15; 3(2).

39. Kavitha K, Kumar MR, Dakshayani S, SD JS. Bilayer tablet technology: An overview. Journal of Applied Pharmaceutical Science. 2011; Oct 30(Issue): 43-7.

40. Parashar B, Chauhan A, Prashar D, Chandel A, Kumar H, Purohit R. Formulation and evaluation aspects of tablets-An overview. Am J PharmTech Res. 2012; 2(1): 2249-3387.

41. Pharmacopoeia I. Government of India, Ministry of Health and Family Welfare, Controller of Publication, New Delhi, India, Vol. 1-2. Received 14th September 2014 Revised 21st September 2014 Accepted 26th September 2014 J. App. Pharm. Res. 2007; XI (4): 17-23.

42. Agarwal RK, Jain HK, Singhai AK. Estimation of Losartan potassium from tablets. Indian Drugs. 2000; 37(5):26-30.

43. Yeole P, Galgatte U, Babla I, Nakhat P. Design and evaluation of xanthan gum-based sustained release matrix tablets of diclofenac sodium. Indian Journal of Pharmaceutical Sciences. 2006 Mar 1; 68(2).

44. Brniak W, Jachowicz R, Pelka P. The practical approach to the evaluation of methods used to determine the disintegration time of orally disintegrating tablets (ODTs). Saudi Pharmaceutical Journal. 2015; Sep. 1; 23(4): 437-43. https://doi.org/10.1016/j.jsps.2015.01.015

45. M. Kaur, G. Kaur, S. Sharma, H. Kaur. Overview on stability studies. International Journal of Pharmaceutical, Chemical and Biological Sciences. 2013; Nov. 3(4): 1231-41. https://doi.org/10.1080/25740881.2020.1844233

Received on 22.12.2023 Revised on 12.04.2024

Accepted on 20.06.2024 Published on 24.12.2024

Available online from December 27, 2024

Research J. Pharmacy and Technology. 2024;17(12):5915-5922.

DOI: 10.52711/0974-360X.2024.00897

Number	MCC	HPMC K100	PVP K30	Drug release	Wetting time	Desirability
1	65.000	50.000	20.000	96.507	49.684	0.570	Selected