DESIGEN, FORMULATION AND EVALUATION OF EFFERVESCENT …

[Pages:7]WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

Gayke et al.

World Journal of Pharmacy and Pharmaceutical Sciences

SJIF Impact Factor 6.647

Volume 6, Issue 9, 2034-2040

Research Article

ISSN 2278 ? 4357

DESIGEN, FORMULATION AND EVALUATION OF EFFERVESCENT TABLET OF ALENDRONATE SODIUM WITH VITAMIN D3

Gayke A. U.*, Aglawe S. B., Sancheti V. P. and Mohan R. S. S. N. D. College of Pharmacy, Babhulgaon, Yeola. Tal.- Yeola, Dist.- Nashik. 423401.

Article Received on 21 July 2017,

Revised on 10 August 2017, Accepted on 31 August 2017,

DOI: 10.20959/wjpps20179-10155

ABSTRACT Alendronate sodium is a bisphosphonates which has antiresorptive effect which is implicated in the prophylaxis and treatment of osteoporosis. The objective of the present investigation is to formulate

effervescent tablet of Alendronate sodium with Vitamin D3 against

*Corresponding Author Gayke A. U. S. N. D. College of Pharmacy, Babhulgaon, Yeola. Tal.- Yeola, Dist.Nashik. 423401.

osteoporosis thereby improving patient compliance. Effervescent tablet is a tablet intended to be dissolved or dispersed in water before administration. Effervescent tablets were formulated using Tartaric acid and sodium bicarbonate as effervescent composition by wet granulation. Formulation was evaluated for weight variation, thickness, hardness, solution time, pH of solution & content uniformity. The

Effervescent tablet of Sodium Alendronate and Vitamin D3 is a new pharmaceutical

formulation to be taken orally and offering a considerable advantage: avoidance of gastro-

intestinal disorders, to the limits of the possible. As compared to the pure drug and marketed

tablet, this formulation displayed significantly effective in the oral osteoporosis treatment in

post-menopausal women.

KEYWORDS: Effervescent tablet, Alendronate sodium, Vitamin D3, Osteoporosis.

INTRODUCTION The oral dosage forms are the most popular way of drug administration despite having some disadvantages like slow absorption and thus onset of action is prolong. This can be overcome by administrating the drug in liquid from but, many APIs have limited level of stability in liquid form. So, Effervescent tablets acts as an alternative dosage form.[1] Effervescent tablet is a tablet intended to be dissolved or dispersed in water before administration. In addition to active ingredients, it generally contains mixture of acids/acid salts and carbonate and hydrogen carbonates which release carbon dioxide when mixed with water.[2] This reaction



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occurs in presence of water, even with small amount as catalyzing agent, and because water is one of the reaction products, it accelerates the rate of reaction, leading to difficulty in stopping the reaction. For this reason, the whole manufacturing and storage of effervescent products is planned by minimizing the contact with water.[3] Alendronate sodium is a BCS class III bisphosphonate, used in the treatment of osteoporosis. Which acts as a potent, specific inhibitor of osteoclast-mediated bone resorption.[4] Colecalciferol (vitamin D3) is a secosterol that is the natural precursor of the calcium-regulating hormone calcitriol (1,25dihydroxyvitamin D3).[5,6] This study seeks to formulate effervescent tablet of Alendronate sodium with cholecalciferol, which limits the amount of time in which the bisphosphonate is in contact with the Oesophageal tissue, thus minimizing the risk of irritation and provide vitamin D3 nutrition during bisphosphonate treatment to facilitate normal bone formation and mineralization while minimizing the occurrence of or potential for the complications associated with vitamin D insufficiency, such as hypocalcaemia and osteomalacia.[7,8]

MATERIALS AND METHODS Materials Alendronate sodium trihydrate was obtained from Apex Healthcare Ltd., Ankleshwar (Gujarat), as a gift sample. Vitamin D3, Citric acid, PVP, Sodium bicarbonate, Sodium saccharine, Tartaric acid, Maltodextrin, Sodium metabisulphite, Boric acid, Sodium benzoate, color and flavor were procured from SciTech Specialities Pvt. Ltd., Sinnar (Maharashtra). All the APIs and excipients used were of analytical grade.

Method



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Table 1: Composition of formulations F1-F9.

Ingredients

Formulation (mg/tab.)

F1 F2 F3 F4 F5 F6 F7 F8 F9

Blend `A'

Sod. alendronate 70.00 70.00 70.00 70.00 70.00 70.00 70.00 70.00 70.00

Tartaric acid

1780.8 1663.591558.991462.561431.491551.17 1571.7 1553.131572.67

PVP

4.3 6.45 4.3 4.3 4.3 4.3 4.3 4.3 4.3

Water

Q.S. Q.S. Q.S. Q.S. Q.S. Q.S. Q.S. Q.S. Q.S.

Blend `B'

Sod. bicarbonate 1780.781839.941890.791931.322044.091881.411906.031883.751907.21

Sod. saccharine

8.6 12.9 17.2 21.5 17.2 12.9 17.2 15.05 15.05

Vitamin D3 Citric acid

2

2

2

2

2

2

2

2

2

4.3 8.6 12.9 17.2 21.5 25.8 21.5 21.5 21.5

Maltodextrin

132 132 132 132 132 132 132 132 132

Sod. metabisulphite 8.6 8.6 8.6 8.6 8.6 8.6 8.6 8.6 8.6

Sunset yellow color 2.15 2.15 2.15 2.15 2.15 2.15 2.15 2.15 2.15

Lemon flavor

86 129 172 215 129 172 129 172 129

Polomint flavor

8.6 12.9 17.2 21.5 25.8 25.8 23.65 23.65 23.65

Lubrication blend

Sodoium Acetate 90.37 90.37 90.37 90.37 90.37 90.37 90.37 90.37 90.37

PEG 600

21.5 21.5 21.5 21.5 21.5 21.5 21.5 21.5 21.5

Total

4000 4000 4000 4000 4000 4000 4000 4000 4000

Evaluation Parameters 1. Tablet Thickness Ten tablets of each formulation were evaluated for thickness and diameter using a calibrated dial caliper.[2]

2. Tablet weight variation Twenty tablets were randomly selected and accurately weighed. Results are expressed as mean values ? SD.[9]

3. Friability Test The friability of tablets was determined using Roche Friabilator. It is expressed in percentage (%). Twenty tablets were initially weighed and transferred into Friabilator. The Friabilator was operated at 25 rpm for 4 minutes or run up to 100 revolutions. The tablets were weighed again. The % friability was then calculated by the following formula.[10] Percentage Friability = W ? W0 ? 100 / W

Where, W0 = initially weight W = weight after friability. Percentages Friability of tablets less than 1 % are considered acceptable.



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4. Hardness The hardness of the tablets was determined using Precision dial type hardness tester. It is expressed in kg/cm2. Three tablets were randomly picked and hardness of the tablets was determined.[11]

5. pH of the Solution pH solution was determined with one tablet in 200 ml of purified water at 20 ? 1?C by using pH meter (HI 2211, HANNA), immediately after completing the dissolution time.[12]

6. Solution Time The solution time is indicating the time required to dissolve the tablet in 200ml of water at 17.5 ? 2.5C.[13]

7. Drug Content Uniformity Drug content analysis of Alendronate sodium Weigh and powder 20 tablets. Weigh accurately a quantity of the powder containing about 25 mg of Alendronate sodium was taken in a 25 ml volumetric flask and dissolved in around 15 ml of distilled water, finally filled up to the mark by distilled water to get a sample solution of 1 mg/ml. Then appropriate dilutions was done from the sample solution using sodium-1, 2napthoquinone-4-sulphonate reagent and 0.01 M NaOH. Absorbance of the resulting brown colored solution was measured at 525 nm using double beam UV spectrophotometer (1600, shimadzu) against a blank.[14]

Drug content analysis of Vitamin D3 Weigh and powder 10 tablets. Weigh accurately about 12.5 gm of the powder into a 100 ml volumetric flask and sufficient amount of Methanol: water (97:3) was added to dissolve properly. Then appropriate dilution was done and analyzed by HPLC instrument (Shimadzu LC-2010A) at 264 nm.[14]

8. Panel Testing (Human Subjects) In vivo taste evaluation carried out on a trained taste panel of 5 healthy volunteers with organoleptic sense, with their prior consent. On placing the dosage form in mouth for 60 seconds, bitterness recorded against pure drug.[15]



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RESULTS AND DISCUSSION Table 2: Evaluation Parameters.

Formulation code

F1 F2 F3 F4 F5 F6 F7 F8 F9

Thickness ? S.D. (mm) (n = 5) 5.85 ? 0.01 5.64 ? 0.015 5.976 ? 0.01 5.89 ? 0.021 6.07 ? 0.015 5.07 ? 0.02 5.78 ? 0.005 5.86 ? 0.01 6.0 ? 0.003

Evaluation parameter

Hardness ? S.D. Friability

(kg/cm2) (n = 5)

(%)

5.6 ? 0.1

0.31?0.02

5.5 ? 0.152

0.24?0.02

6.1 ? 0.152

0.47?0.03

5.5 ? 0.2

0.12?0.01

5.2 ? 0.1

0.46?0.04

5.8 ? 0.057

0.26?0.03

5.9 ? 0.2

0.22?0.01

5.6 ? 0.152

0.27?0.03

5.6 ? 0.057

0.18?0.03

Average weight variation (n=10)

4.005 ? 0.005 3.910 ? 0.01 3.890 ? 0.015 3.973 ? 0.006 3.93 ? 0.013 3.895 ? 0.011 4.008 ? 0.005 3.925 ? 0.013 4.004 ? 0.005

Table 3: Evaluation of Solution time, pH of solution & Drug content.

Formulations Solution time (sec.)

F1

53.83 ? 0.071

F2

54.09 ? 0.066

F3

58.49 ? 0.09

F4

52.54 ? 0.155

F5

50.46 ? 0.101

F6

44.83 ? 0.120

F7

46.08 ? 0.026

F8

56.42 ? 0.065

F9

57.68 ? 0.070

pH of solution

5.01 ? 0.050 5.24 ? 0.025 5.41 ? 0.045 6.02 ? 0.015 5.65 ? 0.030 5.78 ? 0.020 5.48 ? 0.036 5.32 ? 0.025 5.6 ? 0.020

Drug content (%)

ALS

Vit.D3

99.39 ? 0.069 198.112 ? 0.027

99.23 ? 0.060 196.24 ? 0.034

99.17 ? 0.083 196.44 ? 0.036

99.19 ? 0.092 198.10 ? 0.031

99.73 ? 0.063 197.04 ? 0.025

99.68 ? 0.081 196.77 ? 0.030

99.10 ? 0.072 197.16 ? 0.045

99.44 ? 0.057 197.17 ? 0.073

99.85 ? 0.029 199.03 ? 0.016

Table 4: Taste Analysis of Formulations.

Formulations

I

F1

Very sour

F2

Slightly sour,

good

F3

Good but sweet

F4

Basic, Sweet

F5

After Metallic

F6

After Metallic

F7

Sweet

F8

OK

F9

OK

II Very sour Slightly sour, good Good but sweet Basic, Sweet

After Metallic After Metallic, slightly bitter OK OK

OK

Volunteer

III

IV

V

Sour

Very sour

Sour

Very sour

Very slightly Slightly sour

sour, good

Good but sweet Good

Good

Basic, Sweet Basic, very Basic, very

sweet

sweet

After Metallic After Metallic After Metallic

After Metallic, After Metallic, After Metallic,

slightly bitter excess polo slightly bitter

Sweet

Sweet

Sweet

slightly orange slightly orange OK

feel, good

feel, good

OK

OK

OK



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All the tablets were evaluated for hardness, friability, weight variation, pH of the Solution,. Drug Content Uniformity, Panel Testing (Human Subjects). Formulations of various effervescent composition show variation in the pH of solutions and In-vivo taste evaluation by panel test, formulation F9 shows more popularity and having better taste than others.

CONCLUSION The Effervescent tablet of Sodium Alendronate and Vitamin D3 is a new pharmaceutical formulation to be taken orally and offering a considerable advantage: avoidance of gastrointestinal disorders, to the limits of the possible. Another aspect of this invention is that the absorption of the active ingredient is faster when compared to the tablet form; consequently an enhanced bioavailability of the active ingredient is probable. As compared to the pure drug and marketed tablet, effervescent tablet of Alendronate sodium plus Vitamin D3 displayed significantly effective in the oral osteoporosis treatment in post-menopausal women.

REFERENCES 1. A. K. L. Kabir, "Formulation Development of Verapamil Hydrochloride Tablet by

Effervescent Method", Stamford Journal of Pharmaceutical Sciences, 2010; 3(1): 34-37. 3. H. Stahl, "Effervescent Dosage", Pharmaceutical Technology Europe Magazine, April 2003; 25-28. 2. K. R. Srinath, "Formulation and Evaluation of Effervescent tablets of Paracetamol", International Journal of Pharmaceutical Research & Development, 2011; 3(3): 12-76104. 3. H. Stahl, "Effervescent Dosage", Pharmaceutical Technology Europe Magazine, April 2003; 25-28. 4. F. Karamustafa, "Bisphosphonate and Alendronate- Scientific Review", FABAD J. Pharm. Sci., 2006; 31: 31-42. 5. Merck Sharp and Dohme Corp., "Full Prescribing Information for FOSAMAX", Initial U.S. Approval: 1995; Revised, June 2012; 1-23. 6. Teva Pharmaceuticals USA, "Highlights of Prescribing Information of Alendronate Sodium Tablet", May 2012; 1-30. 7. A.V. Katdare, "Effervescent Alendronate Formulation", Patent no.: US 5, 1998; 853-759: 1-4.



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8. G.A. Daifotis, "Combination for Inhibiting Bone Resorption Comprising a Bisphosphonate (Alendronate) and a Vitamin d (Cholecalciferol)", Publication no.: EP1758594 A1, 2007; 1-5.

9. Srinivas Pannala, Mahalaximi Rathnanand, "Preparation and in vitro evalution of nizatidine immediate release tablet", International Journal of Pharm Tech Research, 2011; 1688-1692.

10. Janugade B.U., Patil S. S., Patil S.V., Lade P.D. "Formulation and evaluation of PressCoated montelukast sodium tablets for pulsatile drug delivery system", Int. J. ChemTech Res., 2009; 690-695.

11. H.K. Patel, "Formulation and Evaluation of Effervescent Tablet of Paracetamol and Ibuprofen", International Journal for Pharmaceutical Research Scholars, 2012; 1: I-2, 509-520.

12. A. Aslani, "Formulation, Characterization and Physicochemical Evaluation of Potassium Citrate Effervescent Tablets", Advanced Pharmaceutical Bulletin, 2013; 3(1): 217-225.

13. H. K. Patel, "Formulation and Evaluation of Effervescent Tablet of Paracetamol and Ibuprofen", International Journal for Pharmaceutical Research Scholars, 2012; 1: I-2, 509-520.

14. S. S. Panda, "Spectrophotometric Determination of Alendronate Sodium by Using Sodium-1, 2-Napthoquinone-4-Sulphonate", International Journal of Pharmaceutical Sciences and Nanotechnology, 2012; 4(4): 1563-1568.

15. S. B. Thoke, "Review On: Taste masking approaches and Evaluation of Taste Masking", International Journal of Pharmaceutical Sciences, 2012; 4(2): 1895-1907.



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