Comparative Invitro Evaluation of Commercially ...

International Journal of Advances in Pharmacological Sciences Volume 2, No.1-2, January-December 2012, pp. 25-30 @ Research Sciences Press, (India)

Comparative Invitro Evaluation of Commercially Available Rabeprazole Enteric Coated Tablets *

M. S. Neeharika*, T.Neelima Rani**, K.Susmitha***

Assistant Professor, Department of Pharmaceutics, Raghu College of Pharmacy, Dakamarri, Bheemili, Visakhapatnam, Andhra Pradesh, India. **Malla Reddy Pharmacy College, Dhulapally, Secunderabad, Andhra Pradesh, India. ***Al-Ameer College of Pharmacy, Gudilova, Anandapuram, Visakhapatnam, Andhra Pradesh, India. Email: [email protected] Abstract:-The present study is concerned with the investigation and comparison of physico-chemical properties( thickness, hardness, weight variation, friability and disintegration) and invitro dissolution of the drug along with drug content (assay) for different brands of tablets containing Rabeprazole (20mg, 10mg) prepared by various pharmaceutical industries under different trade names. All the brands passed all the official tests as prescribed by the Pharmacopoeia. All the brands were within the limit when tested for thickness, weight variation, hardness, friability and disintegration. The amount of drug obtained and percentage purity is less when compared to that of labeled claim. Among the four brands, both 20 mg(B) and 10 mg(b), brand 1 i.e. B1 and b1 was found to have more amount of the drug and brand 2 i.e. B2 and b2 was found to have less amount of the drug. The U.V. Spectrophotometric method for the assay of Rabeprazole tablets used in this study is simple, inexpensive, reproducible and easy to use and could be used in routine monitoring of the quality of the Rabeprazole sodium tablets, especially in the absence of high technology equipment. Key Words: Rabeprazole sodium, Pharmacopoiea, Spectrophotometry, Thickness, Weight variation, Hardness, Friability, Disintegration, Dissolution. INTRODUCTION: Rabeprazole sodium is chemically 2-[[[4-(3-Methoxypropoxy)-3-methyl-2-pyridyl]methyl]sulfinyl]benzimidazole sodium which has been widely used in the treatment of peptic ulcer. A wide variety of Rabeprazole tablets are available in the market. Rabeprazole sodium comes under the class of proton pump inhibitor. The main purpose of an oral tablet is to deliver a certain and defined amount of drug to the human body through GI system. Studies on bioavailability of drugs from a given study showed that in many situations tablets with same drug and drug content did not give the same therapeutic response. Formulation additives in the tablet, physical form of the drug used in the tablet and manufacturing process vary from manufacturer to manufacturer, which is responsible for variation in the observed dissolution profile and therapeutic effect. Rabeprazole tablets are available as enteric coated tablets. Enteric coatings are those which remain intact in the stomach but will dissolve and release the contents once it reaches the small intestine. Their prime intension is to delay the release of drugs which are inactivated by the stomach contents or may cause nausea or bleeding by irritation in gastric mucosa. Now a day, many pharmaceutical companies are manufacturing the drugs for their commercial purpose with insufficient active ingredient in the dosage form as they claimed on the strip. So, the study was undertaken with the objective of evaluating different brands of commercially available Rabeprazole enteric coated tablets to get awareness about the pharmaceutical company that gives appropriate active ingredient present in dosage forms released into the market. Rabeprazole tablets are available in 20mg and 10mg doses in the market. In the present study we are comparing 20mg and 10mg tablets of different brands available in the market. The physical parameters weight variation, thickness, hardness, friability, disintegration, dissolution and assay were considered during the present study. MATERIALS AND METHODS: Instrumentation For the analysis of Rabeprazole content in the dosage forms, EI Double beam UV-VIS Spectrophotometer Model No: ELSCOSL210 with 1cm matched quartz cells were used. Other equipments used are USP disintegration apparatus, USP Type-II dissolution apparatus, Roche friabilator, High precision balance and pH meter.

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Materials & Reagents Reference Rabeprazole tablet is a gift sample from Dr. Reddy’s Laboratories limited. The four brands were obtained from a retail pharmacy. PHYSICOCHEMICAL PARAMETERS: Uniformity Of Weight The test was carried out on 20 tablets as per the procedure specified in USP. The average weight and maximum % deviation were calculated. Hardness Test The hardness test was carried out for 5 tablets using Monsanto hardness tester. The average hardness of the tablets was obtained. Thickness The thickness of the tables was calculated by the use of vernier calipers. Friability test The % friability of the tables of each brand was calculated by the use of Roche friabilator. It should be less than 1%. % Friability = (1- W/W0) X 100 Where, W = Initial weight of 20 tablets. W0 = Weight of 20 tablets after 100 revolutions. Disintegration Test The disintegration test was carried out according to USP procedure on six tablets using disintegration test apparatus with discs in 0.1N HCL (pH 1.2) maintained at 37°C ± 2°C for 2 hours. After 2 hours 0.1N HCL was replaced with phosphate buffer 6.8 pH. A disc was added to each tube and operated for further 60 minutes. The disintegration time of each tablet was recorded. Dissolution Study Drug release studies were carried out using a USP type II dissolution test apparatus at 100 rpm for 2 hr in 0.1 N HCl (900 ml) maintained at 37°C ± 0.5°C. 10 ml of sample was taken and sample was analyzed using UV spectrophotometer at 260 nm. Then the dissolution medium was replaced with pH 6.8 phosphate buffer (900 ml) and tested for drug release for 1 hr at same temperature and same rotation speed. After 5, 10, 15, 30, 45 and 60 minutes, 10 ml of the samples were taken out and 10 ml Volume of fresh phosphate buffer pH 6.8 was added to kept volume of dissolution medium constant and sample was analyzed using UV spectrophotometer at 284 nm. Assay The enteric coated tablets of Rabeprazole sodium were tested for their drug content. Ten tablets were finely powdered; quantities of the powder equivalent to 20 mg of Rabeprazole sodium were accurately weighed and transferred to a 100 ml of volumetric flask. The flask was filled with phosphate buffer pH 6.8 and mixed thoroughly. Volume was made up to mark with phosphate buffer pH 6.8 and filtered. The absorbance of the resulting solution was measured at the 284nm using a UV-Vis double beam spectrophotometer and percent purity was determined. RESULTS AND DISCUSSION All the brands exhibited good hardness strength, which is required for safe handling and transportation. Brand 1 exhibited maximum hardness while all the other brands exhibited similar hardness. All the brands had a friability of less than 1%. Tablets having fewer tendencies to generate powder on handling and transportation will have low friability values. The content of Rabeprazole in each tablet brand was within the limits prescribed by U.S.P.

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International Journal of Advances in Pharmacological Sciences Volume 2, No.1-2, January-December 2012, pp. 25-30 @ Research Sciences Press, (India) All the brands of tablets passed the weight variation test. According to I.P., if the tablets are uniform in weight, it is likely that the tablets will be uniform in drug content also. Hence, I.P. prescribes only weight variation test on tablets when the drug forms the major bulk of the tablet. As all the brands passed the weight variation test, it is concluded that all the tablets are uniform in drug content also. All the brands of tablets passed the U.S.P disintegration test indicating that they will completely disintegrate in the intestine within 2 hours but no disintegration in the stomach. All the brands of Rabeprazole tablets passed the dissolution test as prescribed by U.S.P. Even though all brands passed the dissolution test as prescribed by U.S.P., there was variation in Rabeprazole dissolution rate from brand to brand. Table 1: Physical Evaluation Of Different ‘B’ Brands Of Rabeprazole Tablets PHYSICAL B1 B2 B3 PARAMETER

B4

Weight variation

2.4%

4.6%

3.7%

1.9%

Thickness

3.6mm

3.7mm

3.7mm

3.8mm

Hardness

3 Kg/sq.cm

2.5kg/sq.cm

2.5 kg/sq.cm

2.5 kg/sq.cm

Friability

0.62%

0.49%

0.18%

0.33%

No evidence of disintegration for 1 hr




Complete disintegration in 2 hrs




96

90

92

93

Disintegration time: a) In 0.1 N HCl (gastric fluid) b) In 6.8 pH phosphate buffer (intestinal fluid) % Purity

Table 2:Physical Evaluation Of Different ‘B’ Brands Of Rabeprazole Tablets PHYSICAL PARAMETER

b1

b2

b3

b4

Weight variation

2%

3.8%

1.96%

2.2%

Thickness

3.6mm

3.7mm

3.7mm

3.8mm

Hardness

3 kg/sq.cm

2.5 kg/sq.cm

2.5 kg/sq.cm

2.5 kg/sq.cm

Friability Disintegration time:

0.26%

0.33%

0.48%

0.54%









96.5

91

91

93

a) In 0.1 N HCl (gastric fluid) b) In 6.8 pH phosphate buffer (intestinal fluid) % Purity

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Table 3: DISSOLUTION PROFILE FOR BRAND ‘B’ IN 0.1 N HCl % of drug dissolved

Time (hrs) 2

B1

B2

B3

B4

0.12 ± 0.06

0.43 ± 0.04

0.36 ± 0.08

0.22 ± 0.07

Table 4: DISSOLUTION PROFILE FOR BRAND ‘b’ IN 0.1 N HCl % of drug dissolved

Time (hrs) 2

Time (min) 0

b1

b2

b3

b4

0.12 ± 0.04

0.46 ± 0.08

0.32 ± 0.03

0.21 ± 0.05

Table 5: Dissolution Profile For Brand ‘B’ In Ph 6.8 Phosphate Buffer Cumulative % drug dissolved B1 B2 B3 0 0 0

B4 0

5

20 ± 0.12

14 ± 0.17

16 ± 0.19

18 ± 0.11

10

34 ± 0.14

36 ± 0.16

31 ± 0.17

34 ± 0.18

15

46.3 ± 0.18

52 ± 0.14

52 ± 0.13

48 ± 0.16

30

65.25 ± 0.13

71 ± 0.12

63.62 ± 0.14

68 ± 0.14

45

82.95 ± 0.16

82 ± 0.19

78.34 ± 0.17

84 ± 0.12

60

95 ± 0.15

91 ± 0.15

92 ± 0.16

93 ± 0.15

Figure 1: Dissolution Profile For Brand ‘B’ In Ph 6.8 Phosphate Buffer

CUMULATIVE % DRUG DISSOLVED

100 90 80 70 60

B1

50

B2

40

B3

30

B4

20 10 0 0

20

40 TIME (min)

28

60

80

International Journal of Advances in Pharmacological Sciences Volume 2, No.1-2, January-December 2012, pp. 25-30 @ Research Sciences Press, (India) Table 6: Dissolution Profile For Brand ‘B’ In Ph 6.8 Phosphate Buffer Cumulative % drug dissolved b1 b2 b3 0 0 0

Time (min) 0

B4 0

5

18 ± 0.11

15 ± 0.14

16.55 ± 0.16

16.25 ± 0.11

10

33 ± 0.12

32 ± 0.18

41.8 ± 0.15

33.6 ± 0.16

15

41.5 ± 0.19

53 ± 0.16

53.9 ± 0.18

55 ± 0.17

30

66.5 ± 0.16

76 ± 0.15

59.5 ± 0.13

78.5 ± 0.14

45

82.5 ± 0.13

81 ± 0.19

70.3 ± 0.17

82 ± 0.12

60

96.5 ± 0.18

90 ± 0.13

91 ± 0.12

93 ± 0.15

Figure 2: Dissolution Profile For Brand ‘B’ In Ph 6.8 Phosphate Buffer

CUMULATIVE %DRUG DISSOLVED

120 100 80 b1

60

b2 40

b3 b4

20 0 0

10

20

30

40

50

60

70

TIME (min)

CONCLUSION: Almost all the brands have passed all the official tests prescribed by USP. Formulation additives in the tablet, physical form of the drug used in the tablet and manufacturing processes vary from manufacturer to manufacturer which is responsible for the variation in the observed dissolution profiles. It is an alternative to determine Rabeprazole sodium in the pharmaceutical dosage forms that contain it as unique active principle with quite satisfactory results for the specific purposes of its design. We strongly recommend the manufacturers to change their manufacturing process to meet the requirements regarding the amount of the drug present in the dosage form as per label claim so that there will be better invitro performance and thereby better in-vivo performance of the Rabeprazole enteric coated tablets. ACKNOWLEDGEMENT We are very thankful to management of Raghu College of Pharmacy, Dakamarri, Bheemili, Visakhapatnam for providing necessary facilities to carry out the research work. REFERENCES: 1. H.P. Rang, M.M. Dale “Pharmacology” 6th edition, Page no: 386-389. 2. Aulton M.; Pharmaceutics: The Science of Dosage Form Design; International Student Edition: 304-321, 347-668. 3. Ansel H., Allen L. and Jr. Popovich N.; Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems; Eighth: 227-259.

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