Publication Ref No.

: IJPRD/2010/PUB/ARTI/VOV-1/ISSUE-12/FEB/007

ISSN 0974 9446

FORMULATION AND EVALUATION OF ORALLY DISINTEGRATING TABLETS OF SERTRALINE Suhas M. Kakade1*, Vinod S. Mannur1, Ravindra V. Kardi1, Ketan B. Ramani1, Ayaz A. Dhada1 Department of Pharmaceutics, K.L.E. Universitys college of pharmacy, J.N.M.C. Campus, Belgaum 590010, India. Email: suhaspharma@yahoo.com
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Suhas Kakade

ABSTRACT There is an increasing demand for more patient compliant dosage form and a novel method is the development orally disintegrating tablets which dissolve or disintegrates instantly on the patient tongue or buccal mucosa. It is suited for tablets undergoing high first pass metabolism and is used for improving bioavailability with reducing dosing frequency to minimize side effect and make it more cost effective. Sertraline is practically slightly soluble in water, its rapidly and extensively absorbed after oral administration, the absolute bioavailability is only approximately 44% due to extensive hepatic first pass metabolism. Hence the main objective of the study was to formulate orally disintegrating tablets of sertraline to achieve a better dissolution rate and further improving the bioavailability of the drug. Orally disintegrating tablets prepared by direct compression and using super disintegrants like crospovidone, croscarmellose sodium and sodium starch glycolate designate, designated as three different groups of formulation ( A, B and C) respectively were prepared and evaluated for the precompression parameters such as bulk density, compressibility, angle of repose etc. The prepared batches of tablets were evaluated for hardness, weight variation, friability, drug content, disintegration time and in-vitro dissolution profile and found satisfactory. Among the three groups, group (C) containing crospovidone emerged as the best formulation and showed maximum dissolution rate with 98.49% drug release in 15 min. All three groups of formulations released the drug at faster rates than that of marketed conventional tablets of sertraline. Key-words : Sertraline, Superdisintegrants, Orally disinintegrating tablets.

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Publication Ref No.: IJPRD/2010/PUB/ARTI/VOV-1/ISSUE-12/FEB/007

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INTRODUCTION AND MATERIALS & METHODS INTRODUCTION Recent advance in novel drug delivery system aims to enhance the safety and efficacy of the drug molecule by formulating a dosage form being for the administration.1 Difficulty in swallowing is experienced by patient such as pediatric, geriatric, bedridden, disabled and mentally ill, including motion sickness and sudden episodes of allergic attacks, hence resulting in higher incidence of non-compliance and ineffective therapy.2 To improve the quality of life and treatment compliances of such patients fast disintegrating or orally disintegrating tablets dosage form is abetter alternative for oral medication.3 Orally disintegrating tablets are solid dosage form containing medical substances which disintegrate rapidly, usually within few seconds when placed upon tongue requiring no additional water to facilate swallowing.4 It is suited for tablets undergoing high first pass metabolism and is improving bioavailability with reducing dosing frequency to minimize side effect. Sertraline is a selective serotonin reuptake inhibitor (SSRI) used as an adjuvant in the treatment of depression and anxiety disorder. However, the low aqueous solubility it is rapidly and extensively absorbed after oral administration. The absolute bioavailability is only approximately 44% due to extensive hepatic metabolism.5 Various techniques can be used to formulate orally disintegrating tablets or fast dissolving tablets.6 Direct compression one of the techniques requires the incorporation of a superdisintegrants into the formulation the use or highly water soluble excipients to achieve fast tablet disintegration. Direct compression dose not require the use of water or heat during the formulation procedure and is the ideal method for moisture and heat-labile medications. The aim of purpose work was to formulate and characterization orally disintegrating tablets of sertraline for rapid dissolution of drug and absorption, which may produce the rapid onset of action in the treatment of depression and anxiety disorder. MATERIALS AND METHODS Materials: Sertraline was obtained as a gift sample from Sai Ram Organics Pvt. Ltd. Hydrabad. Crospovidone and Lactose spray dried were gift sample from Signet Chemical Corporation, Mumbai. Croscarmellose sodium, Sodium starch glycolate and Microcrystalline cellulose were gift samples from Sunrise Remedies, Ahmedabad, India. All chemicals and reagents used were of analytical grade. Methods: Prepration of orally disintegrating tablets: Sertraline orally disintegrating tablets were prepared by direct compression method. Different concentration of excipients was used to prepare different groups of orally disintegrating tablets. Compositions of various formulations are shown in Table 1. All the ingridents of the orally disintegrating tablets of sertraline were weighed and mixed in mortar with the help of pestle, then finally 1mg Magnesium Sterate and 1mg Aerosil was added material was slightly compressed on the 8mm flat-faced punch using a Rimek tablet press machine. The total weight of the formulation was maintained 200mg. Evaluation of orally disintegrating tablets of sertraline: All the batches of tablets were evaluated for various parameters like weight variation, friability, hardness, drug content, disintegration and dissolution and results reported in Table 2. 2
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Publication Ref No.: IJPRD/2010/PUB/ARTI/VOV-1/ISSUE-12/FEB/007

ISSN 0974 9446

Weight variation test: Twenty tablets were taken and their weight was determined individually and collectively on a digital weighting balance. The average weight of one tablet was determined from the collective weight. Hardness test: The hardness of the tablet was determined using Monsanto Hardness Tester. Friability test: Six tablets from each batch were examined for friability using Roche Fribilator (Tropical Equipment Pvt. Ltd. Mumbai, India) and the equipment was run for 4min at 25 revolutions per minute. The tablets were taken out, dedusted and reweighted and % friability was calculated. %Friability = (Loss in weight/Initial weight) x 100 Water absorption ratio: A piece of tissue paper folded twice was kept in a Petri dish (internal diameter 5.5cm) containing 6ml of purified water. The tablet was placed on the tissue paper and allowed to wet completely. The wetted tablet was removed and reweighted. Water absorption ratio, R was determined according to the following equation. R = 100 (Wa Wb)/Wb Where Wb and Wb are the weight before and after water absorption, respectively. Wetting time: A piece of tissue paper folded twice was kept in a Petri dish (inter diameter 5.5cm) containing 6ml of purified water. The tablet was placed on the tissue paper and allowed to wet completely. The time required for complete wetting of the tablet was then recorded. Content uniformity test: Five tablets were weighed and powdered, 10 mg of equivalent of sertraline was weighed and dissolved in suitable quantity of methanol, the solution was filtered suitably diluted and the drug content was analyzed using UV spectrometer at 270 nm. In vitro disintegration time: The disintegration test was performed using an USP disintegration apparatus, with distilled water at 240.50C. The time reported to obtain complete disintegration of six tablets were recorded and average was reported. In vitro dissolution testing: Dissolution study was conducted for all the formulation using USP type-II apparatus (Electolab, Mumbai, India.). The dissolution test was performed using 500 ml of phosphate buffer (PH 6.8) was taken as the dissolution medium at 50 rpm and 370C0.50C. Five millilitres of aliquots were periodically withdrawn and the sample volume was replaced with an equal volume of fresh dissolution medium. The samples were analyzed spectrophotometrically at 270 nm.

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RESULT AND DISCUSSION

Sertraline orally disintegrating tablets were prepared by direct compression method. Three different groups (A, B and C) of formulation with variation of tablet excipent were prepared with each group containing three different formulations. Table 2 shows the data obtained from the evaluation of tablets. All batches of the tablets were preliminarily evaluated for various physical parameters such as hardness, friability, drug content, wetting time, water absorption ratio, disintegration and dissolution which were reported in Table no 2. All above properties and value were near to boundary of standard limit. All the tablets maintained hardness in the range 3.44.1kg/cm2. The loss in total weight of the tablets due to friability was in the range of 0.23-0.61%. The drug content in different formulation was highly uniform and in the range of 97-99%. Wetting time is used as an indicator of the ease of tablet disintegration and found to be 17-32sec. (Figure No.1). Water absorption ratio ranged from 18.45-37.89. The result in vitro disintegration were within the prescribe limit and comply with the criteria for orally disintegrating tablets, the value were with 18-43sec. In vitro dissolution studies are shown in table 2 and fig. 2, 3 and 4. The cumulative % of drug release increased in 15 min with increased in the concentration of superdisintegrant. At 10% superdisintegrant level the drug release at the end of 15 min. were found to be 98.49%, 91.36% and 86.15% with crospovidone, croscarmellose sodium and sodium starch glycolate respectively.

CONCLUSION In the present study it can be concluded from the characterization of orally disintegrating tablets of sertraline that formulation containing crospovidone is most acceptable. It was observed that to further increase the drug release from orally disintegrating tablets, solubility enhancement of sertraline required and is under investigation. ACKNOWLEDMENT We acknowledge generous help of Sai Ram Organics Pvt. Ltd. Hyderabad, India. Signet Chemical Corporation, Mumbai, India. And Sunrise Remedies Pvt. Ltd. Ahmadabad, India for providing gift samples of sertraline and superdisintegrants respectively. REFERENCES 1. Kuchekar, B.S., Badhan, A.C., Mahajan, H.S., Mouth Dissolving Tablets: A Novel Drug Delivery System, Pharma Times, 2003, 35, 7-9. 2. Seager, H., Drug-delivery product and the zydis fast dissolving form, J. Pharm. Pharmacol., 1998, 50(4), 375-82. 3. Yutaka, M., Yuki, T., Masanobu, Y., Ryoji, T., Junko, A., Kozo, T., Evalution of the disintegration time of rapidly disintegrating tablets via a novel method utilizing a CCD camera, Chem. Pharm. Bull., 2002, 50(9), 1181-1186. 4. Shu, T., Suzuki, H., Hironaka, K., Ito, K., Studies of rapidly disintegrating tablets in the oral cavity using co-grinding mixtures of mannitol with crospovidone, Chem. Pharm. Bull., 2002, 50, 193-198. 5. Kathleen, P., Sean, C.S., Paul, S.B., Martindale the complete drug reference, 32nd Edn, Pharmaceutical press, UK, 1999, 307-308. 6. Brown, D., Drug Delivery Technol., 2004, 1-4. International Journal of Pharma Research and Development Online 4

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7. Abdelbary, G., Eouani, C., Prinderre, P., Jachion, J., Reynier, J.P., Piccerellel, P.H., Determination of the In vitro Disinetgration Profile of Rapidly Disintegrating Tablets and Correlation with Oral Disinetgration, Int. J. Pharm., 2004, 292, 29-41. 8. Kuchekar, B.S., Badhan, A.C., Mahajan, H.S., Mouth Dissolving Tablets of Salbutamol Sulphate: A Novel Drug Delivery system, Indian Drugs, 2004, 41(10), 592-598. 9. Rajitha, K., Shravan K.Y., Adhukondalu, D., Ramesh, G., Madhusudan, Y., Formulation and Evaluation of Orally Disintegrating Tablets of Buspirone, Int. J. Pharm. Sci. and Nanotechnol., 2009, 1(4), 372-334. 10. Lachman, L., Liberman, H.A., Kanig, J.L., The theory and practice of industrial pharmacy, 3rd Edn, Varghese Pub. House: Bombay, 2003, 293-294.

FIGURES & TABLES Table 1: Formulation of Sertraline Orally Disintegrating Tablets Ingredients Group A A1 Sertaline Lactose (Spray Dried) MCC Crospovidone Croscarmellose Sodium SSG Aspartame Aerosil Mg Stearate 50 96 40 10 2 1 1 A2 50 91 40 15 2 1 1 A3 50 86 40 20 2 1 1 Group B B1 50 96 40 10 2 1 1 B2 50 91 40 15 2 1 1 B3 50 86 40 20 2 1 1 Group C C1 50 96 40 10 2 1 1 C2 50 91 40 15 2 1 1 C3 50 86 40 20 2 1 1

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Table 2: Evaluation data of the prepared sertraline orally disintegrating tablets

Evaluati on Paramet ers Hardnes s (kg/cm2)

Group A A1 A2 A3 B1

Group B B2 B3 C1

Group C C2 C3

3.7 0.02

3.8 0.12

4.1 0.06

3.6 0.03

3.4 0.01

3.9 0.03

3.7 0.06

3.6 0.01

4.1 0.01

Friabilit y (%) Drug content (%) Disinteg ration time (sec.) Wetting time (sec.) Water absorpti on ratio % Cumulat ive drug release

0.40 0.03 97.90

0.33 0.07 98.25

0.23 0.04 99.25

0.61 0.05 98.89

0.43 0.01 99.00

0.56 0.04 99.18

0.34 0.02 97.00

0.38 0.01 98.35

0.44 0.03

98.76

34 2.00 22.00 1.12 27.89 1.123

24 2.00 18.00 0.61 19.84 2.135

18 1.00 17.33 1.55 18.45 2.138

43 0.00 24.87 0.36 30.45 1.638

33 1.00 23.67 0.5 29.79 1.653

20 2.00 22.34 1.58 28.09 1.528

38 2.00 32.39 0.58 37.89 1.345

26 2.00 26.01 1.01 36.37 1.965

21 1.00 25.33 0.59 34.09 1.936

89.73

91.23

98.49

85.11

88.71

91.36

78.26

82.26

86.15

50 45 40 35 Tm ( e .) i e sc 30 25 20 15 10 5 0 A1 A2 A3 B1 B2 B3 C1

Disintegration time Wetting time

C2

C3

For m ulation

Figure 1: Disintegration time and Wetting time of Sertraline orally disintegrating tablets 6
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% Cumulative drug release

100 80 60 40 20 0 0 3 6 9 12 15 18 Time in minutes A1 A2 A3

Figure 2: Drug release profile of group A tablets

100 % Cumulative drug release 80 60 40 20 0 0 3 6 9 12 15 18 Time in minutes B1 B2 B3

Figure 3: Drug release profile of group B tablets

100 % Cumulative drug release 80 60 40 20 0 0 3 6 9 12 15 18 Time in minutes C1 C2 C3

Figure 4: Drug release profile of group C tablets 7

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