Formulation and Evaluation of Orodispersble Tablet

 

Pratiksha S. Deore*, Yashpal M. More, Dr. Avish D. Maru

Department of Pharmaceutics, Loknete Dr. J D Pawar College of Pharmacy, Manur, Tal.

Kalwan – 423501, Dist. Nashik, (MH) India.

*Corresponding Author E-mail: deorepratiksha84@gmail.com

 

ABSTRACT:

The aim of present work is to formulate and develop tablets of promethazine HCL.by using various superdisintegrating agent by direct compression method. The main objective of the study is to increase rapid onset of action of promethazine HCL in the treatment of nausea and vomiting. The orodispersible tablet of promethazine hcl is were prepared by direct compression method. Using different concentration of Crospovidone, croscarmellose sodium Mannitol, lactose, maltose, mg. stearate. The tablet was evaluated by various parameters and result are found to be satisfactory.

 

KEYWORDS: Orodispersible, Super disintegrants, Direct compression, Repimelt.

 

 

INTRODUCTION:

These types of tablets are those when placed in mouth cavity disperse the drug in very rapid manner i.e., instantaneously releasing the drug which dissolve in saliva. ODTs are alternative dosage forms for the patients who are suffering from dysphasia i.e., difficulty in swallowing. The oral administration of drug is most important method for administrating the drugs for systemic effects. Except that the parenteral route is not used routinely for self-administration e.g., insulin. Topical route is only applicable to deliver the drugs into the body for the systemic effect. The administration of the drug by the parenteral route is only beneficial for treating medical emergencies in which the subject is comatose or can’t swallow. Never the less it is probable that at least 90% of all drugs used to provide systemic effects are administered by the oral route. ODTs are the different from traditional tablets in that they are designed to be dispersed on the tongue rather than swallowed whole.

 

ODTs dissolve or disintegrate in the oral cavity without the need of water or chewing. And also it is mainly used for the rapid action, to enhance the bioavailability, accurate dosing, enhance palatability, ease of administration, accurate dosing, having a good patient compliance because most of the people familiar with this route. Drugs present in ODTs do not suffer from the first pass metabolism. This type of drug administration or delivery is becoming popular day by day due to its numerous advantages. ODTs have tremendous advancement in drug delivery, the oral route is the ideal and preferable route for the administration of therapeutic agents because of low-cost therapy, it tends to high level of patient compliance. This article contains an inventive technology, the dosage form containing active pharmaceutical ingredients (API). They disintegrent rapidly, usually in case of seconds, without need for water, providing optimal convenience to the patient.

 

Sailent features

·         Ease of administration

·         No need of water

·         Increased bioavailability

·         More conventional dosage form for uncooperative patients

 

Advantages of ODT

·         It is superior for the traveler and busy persons who does not contain water every time and also suitable for bedridden.

·         Having good mouth feel property it helps to mask the bitterness of medicine.

·         It allows high drug loading.

·         No need of chewing.

·         Rapid drug therapy intervention.

·         It provides rapid absorption of drugs and enhance bioavailability.

 

Disadvantages of ODT:

·         It is hygroscopic in nature, so must kept in dry place.

·         If the dosage form is not formulated properly, it may leave unpleasant taste in mouth.

·         Careful handling is required in case the tablet having insufficient mechanical strength.

 

MATERIALS AND METHODS :

1.       Materials

Promethazine HCl, crospovidone, Crosscarmellose sodium, Mannitol, Mg. stearate, Maltose, Lactose.

 

Table No : 1 List of materials used for the experimental work:

Sr. No.

Ingredients

Name of supplier

Functional Category

1

Promethazine HCL

Balaji Drug, Nashik

Active Pharmaceutical Ingredient

2

Crospovidone

Research Lab, Mumbai

Super disintegrants

3

Crosscarmellose Sodium

Research Lab, Mumbai

Super disintegrants

4

Mannitol

Research Lab, Mumbai

Sweetning agent, Disintegrant

5

Mg. Stearate

Research Lab, Mumbai

Lubricant

6

Maltose

Research Lab, Mumbai

Sweetning agent

7

Lactose

Research Lab, Mumbai

Filler, Diluent

 

2.       METHOD:

Preparation of orodispersible tablet by using direct compression method:

 In the direct compression method of tablet preparation, dry ingredients are thoroughly weighed, mixed and then passed through sieve no.20 again it mixed together and then compressed using 8 mm flat punch on cemach R&D tablet press 8 station compression machine .hardness of the tablet was maintain at 3-3.5Kg/cm2.Tablet weight was maintain at 170 to 180 mg. this technique eliminates the drying step it associate with the wet granulation method .It also reduce the higher cost involved in wet granulation including increase equipment, time, labor, process validation and the energy expenditure .Direct Compression have demands the use of excipients with strictly defined properties .As per the results Direct compression Method is both economical and efficient .Its well suitable for the production of high quality tablets ,which is exhibit low friability ,hardness and excellent dissolution rate .Direct compression can improve the chemical and physical stability of tablets as compared to wet granulation .

 

Formulation of promethazine HCl orodispersible Tablet:

Table No 2: Formulation of promethazine HCl orodispersible tablet 100mg.

Sr. No

Name of Ingredients

F1

F2

F3

F4

F5

F6

F7

F8

F9

1

Promethazine HCL

50

50

50

50

50

50

50

50

50

2

Crospovidone

12

12

12

9

9

9

7

7

7

3

Crosscarmellose sodium

12

9

7

12

9

7

12

9

7

4

Mannitol

10

10

10

10

10

10

10

10

10

5

Mg. stearate

6

6

6

6

6

6

6

6

6

6

Maltose

5

5

5

5

5

5

5

5

5

7

Lactose

Q.s

Q.s

Q.s

Q.s

Q.s

Q.s

Q.s

Q.s

Q.s

 

 

RESULT AND DISCUSSION:

Pre-formulation study:

Identification and Characterization of drug:

a)       Organoleptic properties:

Promethazine HCl received was studying for organoleptic characters such as color, odor and appearance.

 

Table No. 3 Organoleptic properties of Promethazine HCL

Sr.

No

Parameters

Observed Results

Standard Results

1

Color

White

White

2

Odor

Odorless

Odorless

3

Appearance

Crystalline powder

Crystalline powder

 

All the test of Promethazine HCL complies as per I.P. 2014 therefore it’s confirmed that the model drug has good properties.

 

b)      Melting point:

The melting point was determine by capillary method and it was found to be

 

Table No. 3. Melting Point of Promethazine HCl

Parameter

Observed result

Reported results

Melting point

210-212°C

216-218°C

 

c)       UV-Spectrum of Promethazine HCl:

Determination of λ max of Promethazine HCl in Phosphate buffer (pH.6.8):

The Ultra-violet spectroscopic absorbance of Promethazine HCl was done in 0.1M HCl at the 274ʎ max.

 

Fig.no. 1.Calibration curve of Promethazine HCl in phosphate buffer (pH6.8)

 

Table No. 4 Calibration curve of Promethazine HCl in phosphate buffer pH 6.8

Sr. No.

Concentration (μg/ml)

Absorbance at (274nm)

1

5

0.182

2

10

0.398

3

15

0.456

4

20

0.709

5

25

0.826

6

30

0.923

 

d)      FTIR Study (Promethazine HCl):

 

Fig No. 2. FTIR Spectrum of Pure drug Promethazine HCl

 

Table No. 5. Identification of function groups in FT-IR spectrum of Promethazine HCl

Sr. No.

Wave Number

Functional group

1

3704

NH2Asymmetric Stretching

2

3589

NH2 Symmetric Stretching

3

3236

C-H Sym.Stretching

4

3212

C-H Asym. Stretching

5

1642

C=N Stretching +NH2Scissoring

6

1621

Aromatic breathing + NH2Scissoring

7

1584

Aromatic C-C Stretching + NH2 scissoring

8

1531

C-C Stretching +C=N Stretching +NH2 Scissoring

9

1431

C- C Stretching

10

1142

Aromatic Breathing + NH2 Rocking

11

1025

NH2 Rocking + Aromatic C-H in Plane Bending

12

974

Aromatic Deformation + NH 2Rocking

13

738

C-Cl Stretching +C-C-C in plane bending

14

578

C-Cl Stretching +NH2 twisting

 

e)       DSC Study:

Differential Scanning Calorimetry analysis of pure drug were obtained by differential scanning calorimeter (DSC 60 Shimazdu, Japan). The samples were heated in an open aluminum pans at a rate of 100 per min–1 in a 300C to 3000C temperature range under a nitrogen flow of 40 ml/min. Promethazine HCl shows a long and short characteristics endothermic peak at 217.21°C due to its phase transition system

 

Fig No.3. DSC of Promethazine HCl

 

Compatibility Study: (at 40 ̊C/ 75% RH

Table No. 6. Compatibility study of drug with different excipients

Sr No.

Ingredients

Observation (After 30 Days)

1

Promethazine HCL

No Change

2

Promethazine HCL + CP

No Change

3

Promethazine HCL + CCS

No Change

4

Promethazine HCL + Mannitol

No Change

5

Promethazine HCL + Mg. Stearate

No Change

6

Promethazine HCL + Maltose

No Change

7

Promethazine HCL + Lactose

No Change

 

Pre-formulation Studies:

Angle of repose:

The data obtained from the angle of repose for all the formulations were found to be in the range of 21.12°C to 30.10°C, which reveals god flow property.

 

Bulk Density/ Tapped Density:

Bulk density and tapped density for the blend was performed. The bulk density and tapped density for the entire formulation blend varied from 0.26-0.45gm/ml and tapped density varies from 0.35- 0.54gm/ml

 

Evaluation parameter:

Preliminary Study:

a)       Stage 1:

Table No. 7. Pre-Compression Evaluation (Powder)

Sr. No.

Formulation

Code

Bulk Density (gm/ml)

Tapped Density (gm/ml)

Angle of Repose ( ̊ )

Carr’s Index (%)

Hausner’s Ratio

1

F1

0.33

0.35

27.29

11.06

1.16

2

F2

0.26

0.54

24.62

14.19

1.08

3

F3

0.37

0.35

25.68

13.97

1.06

4

F4

0.35

0.42

30.10

15.31

1.11

5

F5

0.45

0.37

28.42

16.44

1.17

6

F6

0.40

0.39

22.31

15.32

1.13

7

F7

0.33

0.54

26.01

13.12

1.22

8

F8

0.29

0.42

21.12

16.02

1.12

9

F9

0.45

0.39

29.09

15.09

1.27

 

b)      Stage II:

Post Compression Evaluation

Table No.8. Post Compression Evaluation (Trial batches)

Sr. No.

Formulation code

Weight variation (mg)

Diameter (mm)

Thickness (mm)

Hardness (kg/cm2)

Friability (%)

1

T1

201

8

3.85

3.99

0.73

2

T2

204

8

3.91

4.25

0.85

3

T3

200

8

3.53

4.31

0.59

4

T4

199

8

3.90

4.25

0.81

5

T5

204

8

3.91

4.40

0.93

6

T6

198

8

3.80

3.70

0.78

7

T7

202

8

3.78

4.0

0.83

8

T8

196

8

3.81

3.70

0.69

9

T9

201

8

3.84

4.01

0.85

 

Hausner’s Ratio:

The hausner’s ratio of the entire formulation varies from 1.06- 1-27, with good flow properties.

 

Carr’s Index:

The % Compressibility of the all 9 formulations is 11.06 –16.44, which is good or in the acceptable range means showing good or fair flowability for proper flow of powder blend.

 

All these results indicated that, the powder mixture possess good flow of powder and compressibility properties.

 

Stage III:

Percent Drug Release

Table No.9. % Drug Release F1 – F5 Batch (In vitro dissolution study)

Sr. No

Time (min)

F1

F2

F3

F4

F5

1

5

31.12

36.19

33.75

35.07

36.41

2

10

40.20

47.39

44.21

43.89

45.82

3

15

52.33

69.81

59.23

56.87

58.72

4

20

63.15

81.22

68.77

69.09

71.89

5

25

82.09

88.13

79.91

81.13

86.74

6

30

90.34

93.84

91.84

92.03

92.89

 

Fig No.4. In vitro dissolution study of F1 – F5 Batch

 

Table No. 10. % Drug Release F6 – F9 Batch (In vitro dissolution study)

Sr. No

Time (min)

F6

F7

F8

F9

1

5

39.64

40.13

41.91

38.93

2

10

47.14

49.20

50.63

49.70

3

51

61.27

60.69

61.67

58.34

4

20

74.62

69.02

69.23

70.21

5

25

89.71

80.27

82.09

83.90

6

30

98.23

93.77

93.24

94.92

 

Fig No.5. In vitro dissolution study of F6 – F9 Batch

 

c)       Stage IV:

Stability Study:

After storage Promethazine HCl orodispersible tablets were analysed the stability study of final trial was done after 3 months by store in stability chamber. The result given in table 11.

 

Table No. 11 Stability Study of the tablet

Evaluation parameter

Before stability

After 1 month storage

After 2-month storage

After 3-month storage

Average weight

200 mg

200 mg

200 mg

200 mg

Hardness

3.41

3.40

3.40

3.40

Friability

0.83

0.83

0.83

0.83

Dispersion time (Sec)

22 Sec

26 Sec

24 Sec

24 Sec

Disintegration time (Sec)

20 Sec

29 Sec

30 Sec

28 Sec

 

CONCLUSION:

In the present work an attempt has been made to develop fast disintegrating tablets of promethazine HCl. By using various superdisintegrants like CCS (croscarmellose sodium) and sodium starch glycolate in different praportionshoe. All the formulations were prepared by the direct compression method. The value of the pre-compression parameters of all the formulations showed good flow properties and compressibility, so these can be used for tablet manufacturing. They passed all the quality control evaluation parameters.as per the I.P. limits. Among all the formulations the F6 formulation shows all of the better results than rest of the other formulations, hence F6 is the optimized formulation.

 

ACKNOWLEGMENT:

We are grateful to the teacher’s and Principal of Loknete Dr. J. D. Pawar College of Pharmacy, Manur, Tal. Kalwan for their helpful guidance.

 

REFERENCES:

1.        BimodalM, Singh SK, Mishra DN Vijaya Kumar SG, Spray dried excipient base: a novel technique for the formulation of orally disintegratinuhg tablets. Chem Pharm Bull 54(1): 99-102

2.        Jain, D. and Amul, M., 2014. A review-formulation & development of orodispersible tablet. IJPE, 4, pp.21-38.) Lachman L, Liberman HA, Kanig Jl. The Theory and Practical of Industrial Pharmacy .

3.        Garud, S.S., Derle, D.V., Valavi, A.B., Shaikh, S.J. and Derle, N.D., 2014. A review on: Orodispersible tablet (ODT) technology-A novel approach to develop the supergenerics. Int. J. Pharm. Sci. Rev. Res, 26(2), pp.231-236.

4.        Arora, P. and Sethi, V.A., 2013. Orodispersible tablets: A comprehensive review. International Journal of Research and Development in Pharmacy & Life Sciences, 2(2), pp.270-284.

5.        Kaushik D, Dureja H, Saini TR. Mouth dissolving tablets: A Review. Indian Drugs 41 (4): 187-193.

6.        Tablets Formulation of tablets/ Disintegration. www.pharmpedia.com,2014

7.        Prasad D, Ghosh T, Ghosh A, A Review on New Generation Orodispersible Tablets and its future prospective. Int Journ Pharm Pharm Sci 2014

8.        Dobetti L (2012). Fast melting tablets: Developments and technologies. Pharm Technol Drug Deliv Suppl 44-50.

9.        Sachan, A.K., 2019. Comparative Study of Natural and Synthetic Superdisintegrants in Orodispersible Metformin Tablet. Asian Journal of Pharmaceutical Research and Development, 7(3), pp.46-53.

10.      Miehlke, S., Lucendo, A.J., Straumann, A., Jan Bredenoord, A. and Attwood, S., 2020. Orodispersible budesonide tablets for the treatment of eosinophilic esophagitis: a review of the latest evidence. Therapeutic Advances in Gastroenterology, 13, p.1756284820927282.

11.      Scaglione, F., Donde, S., Hassan, T.A. and Jannini, E.A., 2017. Phosphodiesterase type 5 inhibitors for the treatment of erectile dysfunction: pharmacology and clinical impact of the sildenafil citrate orodispersible tablet formulation. Clinical Therapeutics, 39(2), pp.370-377.

12.      Cilurzo, F., Musazzi, U.M., Franzé, S., Selmin, F. and Minghetti, P., 2018. Orodispersible dosage forms: biopharmaceutical improvements and regulatory requirements. Drug Discovery Today, 23(2), pp.251-259.

13.      Gupta, D.K., Maurya, A. and Varshney, M.M., 2020. Orodispersible tablets: An overview of formulation and technology.

14.      Wasilewska, K. and Winnicka, K., 2019. How to assess orodispersible film quality? A review of applied methods and their modifications. Acta Pharmaceutica, 69(2), pp.155-176.

15.      Rahane, R.D. and Rachh, P.R., 2018. A review on fast dissolving tablet. Journal of Drug Delivery and Therapeutics, 8(5), pp.50-55.

16.      Ratnaparkhi M, “Formulation and Development of Taste Masked Orally Disintegrating Tablets of Perindopril Erbumine by Direct Compression Method” PAA; 3(5):1-10.

17.      Slavkova, M. and Breitkreutz, J., 2015. Orodispersible drug formulations for children and elderly. European Journal of Pharmaceutical Sciences, 75, pp.2-9.

18.      Rameesa, C.K. and Drisya, M.K., 2015. Orodispersible Tablet: A patient friendly dosage form (a Review). Bali Med. J., 4(1), pp.17-20.

19.      Wasilewska, K. and Winnicka, K., 2019. How to assess orodispersible film quality? A review of applied methods and their modifications. Acta Pharmaceutica, 69(2), pp.155-176.

20.      Abay, F.B. and Ugurlu, T., 2015. Orally disintegrating tablets: a short review. Journal of Pharmaceutics & Drug Development, 3(3), p.303.

21.      Kumari, P.K. and Rao, Y.S., 2019. A Review on Orodispersible Tablets: A Novel Approach. Research Journal of Pharmacy and Technology, 12(8), pp.3993-4001.

22.      Pinho, L.A., Temer, A.C., Ribeiro, C., Sá-Barreto, L.L. and Cunha-Filho, M.S.S., 2018. The popularization of orodispersible tablets in the pharmaceutical market. Infarma-Ciências Farmacêuticas, 30(2), pp.77-84.

23.      Deshmukh, R.S., Bari, M.M. and Barhate, S.D., 2018. Formulation and Evaluation of Orodispersible Tablet of Naratriptan HCl. Asian Journal of Pharmacy and Technology, 8(3).

24.      Kanathe, P., Jain, R., Jain, N. and Jain, S.K., 2021. Formulation and Evaluation of Orodispersible Tablet of Fluvastatin Sodium. Journal of Drug Delivery and Therapeutics, 11(1), pp.42-47.

25.      Verma, S., 2018. A Review on Conventional and Modern Techniques to Develop Orodispersible Films. Asian Journal of Pharmaceutics (AJP): Free full text articles from Asian J Pharm, 12(02).

26.      Sachan, A.K., 2019. Comparative Study of Natural and Synthetic Superdisintegrants in Orodispersible Metformin Tablet. Asian Journal of Pharmaceutical Research and Development, 7(3), pp.46-53.

27.      Hobbs, D., Karagianis, J., Treuer, T. and Raskin, J., 2013. An in vitro analysis of disintegration times of different formulations of olanzapine orodispersible tablet: a preliminary report. Drugs in R&D, 13(4), pp.281-288.

28.      Gupta, S., Kesarla, R., Chotai, N., Misra, A. and Omri, A., 2017. Systematic approach for the formulation and optimization of solid lipid nanoparticles of efavirenz by high pressure homogenization using design of experiments for brain targeting and enhanced bioavailability. Biomed research international, 2017.

29.      Panda, N., Reddy, A.V., Reddy, G.S. and Panda, K.C., 2015. Formulation design and in vitro evaluation of zolmitriptan immediate release tablets using primojel and AC-Di-Sol. Journal of Pharmaceutical Sciences and Research, 7(8), p.545.

30.      Puttewar, T.Y., Kshirsagar, M.D., Chandewar, A.V. and Chikhale, R.V., 2010. Formulation and evaluation of orodispersible tablet of taste masked doxylamine succinate using ion exchange resin. Journal of King Saud University-Science, 22(4), pp.229-240.

31.      Singh, J., Philip, A.K. and Pathak, K., 2008. Optimization studies on design and evaluation of orodispersible pediatric formulation of indomethacin. Aaps Pharmscitech, 9(1), pp.60-66.

32.      Subramanian, S., Sankar, V., Manakadan, A.A., Ismail, S. and Andhuvan, G., 2010. Formulation and evaluation of Cetirizine dihydrochloride orodispersible tablet. Pakistan journal of pharmaceutical sciences, 23(2).

33.      Jain, D. and Amul, M., 2014. A review-formulation & development of orodispersible tablet. IJPE, 4, pp.21-38.

34.      Radke, R.S., Jadhav, J.K. and Chajeed, M.R., 2009. Formulation and evaluation

35.      Kapadekar Tejas, Deshmukh Ganesh. A Review on Orodispersible Tablets: A Novel Approach. Research J. Pharm. and Tech 2019; 12(8): 3993-4001. doi: 10.5958/0974-360X.2019.00688.7

36.      Sneha B. Patel, Manish N. Vaghani, Jitendra Singh Yadav. A Current Review on Orodispersible Tablet. Research J. Pharm. and Tech. 8(5): May, 2015; Page 637-646. doi: 10.5958/0974-360X.2015.00102.X

37.      Vishali T, Damodharan N. Orodispersible Tablets: A Review. Research J. Pharm. and Tech 2020; 13(5): 2522-2529. doi: 10.5958/0974-360X.2020.00449.7

38.      Anjan K. Mahapatra, Ranjit P. Swain, B. Revathi, N. Nirisha, P.N. Murthy. Orodispersible Tablets: A review on Formulation Development Technologies and Strategies. Research J. Pharm. and Tech. 6(9): September 2013; Page 941-953.

39.      Fady A. Malaak, Khalid Abu Zeid, Shahinaze A. Fouad, Mohamed A. El-Nabarawi. Orodispersible Tablets: Novel Strategies and future challenges in Drug Delivery. Research J. Pharm. and Tech. 2019; 12(11):5575-5582. doi: 10.5958/0974-360X.2019.00966.1

40.      DG Umalkar, GV Shinde, GS Bangale, Rajesh KS, RSR Murthy. Design and Evaluation of Orodispersible Tablet of Aceclofenac Using Different Superdisintegrants by 23 Factorial Designs. Research J. Pharma. Dosage Forms and Tech. 2010; 2(2):198-203.

41.      Sharad A. More, Shrinivas K. Mohite. Formulation Development and Evaluation of Orodispersible Tablet of Omeprazole by Using Co-Processed Superdisintegrant. Research J. Pharma. Dosage Forms and Tech. 2012; 4(4): 216-220.

42.      Ramu Samineni, Sumalatha. K, Dharani G, Rachana J, Anitha P, Manasa K. Formulation and Evaluation of Oral Disintegrating Tablets of Montelukast Sodium and Desloratidine. Res. J. Pharma. Dosage Forms and Tech.2019; 11(3):152-158. doi: 10.5958/0975-4377.2019.00026.0

43.      Srinivasa Sastry D, Narayana Charyulu R, Satyanarayana D S, Srilakshmi D. Formulation and Evaluation of Orodispersible Tablets of an Antiulcer Agent. Research J. Pharm. and Tech. 2017; 10(3): 747-750. doi: 10.5958/0974-360X.2017.00140.8

44.      Siddharth Kumar Sahu, Ajazuddin, Tripti Banjare, Swapnil Gupta, Akansha Bhandarkar, Hemlata Sahu, Shradha Devi Diwedi, Pankaj Sahu, Palak Agrawal, Pooja Yadav, Aditi Bhatt, Kailash Sahu, Deeksha Dewangan, HemlataThapa, Deepika, GyaneshSahu, Mukesh Sharma, D. K. Tripathi, Amit Alexander. Formulation and evaluation of orodispersible tablet of montelukast sodium. Research J. Pharm. and Tech. 2018; 11(3): 1112-1118. doi: 10.5958/0974-360X.2018.00209.3

 

 

Received on 04.06.2021              Modified on 13.07.2021

Accepted on 30.07.2021       ©Asian Pharma Press All Right Reserved

Asian J. Res. Pharm. Sci. 2021; 11(4):267-272.

DOI: 10.52711/2231-5659.2021.00042