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Research Article Available online through www.ijrap.net EVALUATION OF MORINGA OLEIFERA GUM AS A BINDER IN TABLET FORMULATION Patil Basawaraj S.*, Soodam Srinivas R., Kulkarni Upendra, Korwar Prakassh G. R.M.E.S College of Pharmacy, Gulbarga, Karnataka, India Received: 08-11-2010; Revised: 26-11-2010; Accepted: 02-12-2010 ABSTRACT Various plant gums have been used as binders in tablet formulations. But still finding novel binder for the manufacture of tablets, in pharmaceutical industry. The Moringa oleifera gum was found its binding property. In the present study Moringa oleifera gum was employed as a binding agent in Chloroquine phosphate tablets at concentrations of 4.0, 6.0 and 8.0 % w/w, in comparison with potato starch. The properties of Moringa oleifera gum were evaluated for angle of repose, bulk density, tapped density, carr s compressibility index and hausner s ratio. The granules were evaluated for moisture content, angle of repose, bulk and tapped densities. The tablets were evaluated for thickness, weight variation, hardness, friability, disintegration time and dissolution profiles. Studies showed that increase in binding concentration of Moringa oleifera gum, increases the hardness, increases the disintegration time, decreases the percentage friability and decreases % cumulative release. Results obtained indicated that Moringa oleifera gum performed as good as potato starch as a binder to Chloroquine phosphate tablets. KEYWORDS: Moringa oleifera gum, Chloroquine phosphate, Potato starch, Binder, Tablets. *Correspondence Address Basawaraj S.Patil Professor, Department of Pharmaceutics RMES College of Pharmacy, Old Jewargi road, Balaji Nager, Gulbaraga. (Karnatka) Mob. No.+919448211308 E-mail: bspatilglb17@gmail.com

INTRODUCTION Binders are agents used to impart cohesive qualities to the powdered material during the production of tablets. They impart cohesiveness to the tablet formulation, which ensures that the tablets remain intact after compression as well as improving the free flowing quality. 1 Binders have been used as solutions in the formulations and the method of preparation. The choice of a particular binding agent depends on the binding force required to form granules and its compatibility with the other ingredients particularly the active drug. 2 Starches from different sources have been evaluated and used as excellent binders in either mucilage or the dry powdered form. 3-5 Maize and potato starches have been in common use and recently cassava starch appeared in the British pharmacopoeia as an official starch for use as binder. Their use has increased in the tropics where previously recognized starches are unavailable. Apart from starches, other natural gums, gelatin, sugar solutions, modified natural and synthetic polymers have been employed with considerable success as binders. In all evaluation, the type and binder concentrations have direct effect on the crushing strength, friability, disintegration time and tablet dissolution. 6 In view of the easy availability of the plant, the exudate from the stem of the tree Moringa oleifera was investigated for its application as a binder in tablet formulation. Moringa oleifera is a small genus of quick growing tree distributed in India with herbarium specimen number S8652 (fig.1&2). The stem of the tree exudes a gum, which is initially white in colour but changes to reddish brown to brownish black on exposure. It is sparingly soluble in water giving a highly viscous solution. It is polyuronide consisting of arabinose, galactose and glucoronic acid in the proportion of 10:07:02, rhamnose is present in traces. 7 In the present work, Moringa oleifera gum has been evaluated for its binding properties in a Chloroquine phosphate tablet formulation in comparison with a standard binder, potato starch. MATERIALS AND METHODS Chloroquine Phosphate (Gift sample from Wintech Pharmaceuticals, Mumbai), Maize starch, Potato starch and Talc (BDH chemicals Ltd.), Magnesium stearate (CDH chemicals Ltd.), Gelatin (BDH chemicals Ltd.), Moringa oleifera gum was isolated in the laboratory. Isolation of Moringa oleifera gum The gum was collected from trees (injured site). It was dried, ground, and passed through sieve no 80. Dried gum (10 g) was stirred in distilled water (250 ml) for 6-8 hours at room temperature. The supernatant was obtained by centrifugation. The residue was washed with water and the washings were added to separate supernatant. The procedure was repeated four more times. Finally the supernatant was made up to 500 ml and treated with twice the volume of acetone by continuous stirring. The precipitated material was washed with distilled water and dried at 50-60 0 C under vacuum. Preparation of granules Chloroquine phosphate and starch (as a diluent) were passed through sieve # 40 and mixed for 20 minutes using laboratory scale double (twin) cone mixer. Granules were prepared by wet granulation method using Moringa oleifera gum and potato starch solutions in concentration of 4.0, 6.0 and 8.0 % w/w, the damp mass was passed through sieve # 12 and granules were dried at 50 0 C for 1hour in a tray drier. The dried material was then passed through sieve # 16. Granule analysis Moisture content analysis 1 gm of the granules was put into a crucible and dried to constant weight in a hot air oven at 105 0 C. the moisture content(mc) was deduced as difference between the initial(wo) and final weight (Wf) of the granules expressed as a percentage and calculated as; 8 MC = 100 ( Wo Wf)/Wo Angle of repose 50 gm of the granules was placed in a plugged glass funnel, which had a distance of 10 cm from the flat surface. The granules were then allowed to flow through the 8 mm funnel orifice by removing the

cotton plug from the funnel orifice. The height of the heap (h) formed as well as the radius of the heap (r) was noted. The angle of repose (θ) was calculated as; 9 θ = tan -1 h/r Bulk and tapped densities Exactly 50 gm of granules was weighed on chemical balance and transferred into a 100 ml measuring cylinder. The cylinder was dropped on a wooden platform from a height of 2.5 cm three times at 2 seconds interval. The volume occupied by the granules was recorded as the bulk volume. The cylinder was then tapped on the wooden platform until the volume occupied by the granules remained constant. This was repeated three times for granules. The data generated was used in calculating the Carr s compressibility index (CI) and Hausner s ratio (HR) for the Moringa oleifera gum and potato starch granules. 10 CI = 100(TD-BD)/ TD HR = TD/BD Preparation of tablets Magnesium stearate, talc and aerosol 200 were mixed with prepared granules (Table 1). These granules were punched to tablets using Rotary punching machine. Characterization of tablets 11 Tablet thickness The thickness of 10 tablets each selected at random from the formulated tablets was determined using a vernier caliper and the mean of these readings was taken as the mean tablets thickness Tablet weight uniformity Twenty tablets were weighed individually using a digital balance with the precision of 0.05 mg and readability of 0.1 mg, from which the mean was calculated and percentage deviations determined Hardness The hardness of tablets was determined individually with the Monsanto hardness tester, following 10 tablets were used and the mean hardness was calculated. Friability The friability of 10 tablets was determined using Roche friabilator (Electrolab, Mumbai). This device subjects the tablets to the combined effect of abrasions and shock in a plastic chamber revolving at 25 rpm and dropping the tablets at a height of 6 inches in each revolution. Preweighed sample of tablets was placed in the friabilator and were subjected to 100 revolutions. Tablets were dedusted using a soft muslin cloth and reweighed. The friability (F) is given by the formula; F = (1 Wo / W ) x 100 Disintegration test The disintegration time of tablets was determined according to the method described in the British Pharmacopoeia 1998. Six tablets were placed in each compartment of the disintegration apparatus, with water thermostated at 37 ± 1 0 C as the medium. The tablets were considered to have passed the test after the 6 tablets passed through the mesh of the apparatus in 15 minutes. Calibration curve for Chloroquine Phosphate A stock solution of Chloroquine Phosphate was prepared by dissolving 100 mg of the drug in 100 ml of 0.1 HCl. Various dilutions of the stock were made and absorbance of the various dilutions were the taken at mass of 343 nm using a UV-Visible spectrophotometer. A plot of absorbance, A against concentration, C of the drug was made and the calibration curve K was determined from the slope of the graph. Dissolution tests Drug release from different formulated tablets was performed using USP XXII, type II apparatus. 900ml of 0.1 N HCl was dissolution medium; paddle was rotated at 75 rpm with bath temperature of 37 ± 1 0 C. At every 10 minutes interval 5 ml of sample was withdrawn from the dissolution medium to maintain the volume constant. After filtration and appropriate dilution, the sample solutions were

analyzed at 343 nm using a UV-Visible spectrophotometer. The amount of drug present in the samples was calculated. RESULTS AND DISCUSSION The pre and post compression parameters data for Chloroquine phosphate granules are shown in Table 2 & 3. The lower bulk and tapped densities exhibited by Moringa oleifera gum and potato starch granules shows that both granules were good flowing. Flow properties of the granules were determined as good as flowability is prerequisite for the preparation of the tablets with an acceptable weight variation. According to literature data excellent flow properties are seen for granules with a carr s compressibility index between 5-15 % and a hausner s ratio below 1.25. 12 All the formulations tested had a carr s compressibility index ranging between 8-11 % while their hausner s ratio was below 1.25. The angle of repose was found to be between 22 0 C-25 0 C. The excellent flow properties were also proved by the narrow weight distribution of the tablets. The analysis of granules moisture content was showed that formulations has the highest moisture content and this could be attributable to the fact that it has larger average grain size 13 which implies that there are large pore size which may trap water and result in high moisture contents. Investigations have shown that moisture contents of 3-5% w/w were appropriate to produce maximum disintegration and dissolution for tablets 14. The hardness of the tablets varies between 4-7 kg/cm 2 Clearly indicating that they are strong tablets and they can withstand the mechanical shocks. This is combined with the friability (less than 1%) of all the formulations demonstrated the effectiveness of the tablets for use as binder. The disintegration time of the tablets varied between 7-10 minutes irrespective of the hardness. The tablet thickness of all the formulations was similar and this can be attributed to their similar bulk and tapped densities and same compressional force used. The drug content is more than 98% in all tablet formulations. Results obtained from the dissolution studies of Chloroquine phosphate tablets using Moringa oleifera gum and potato starch, the drug release profile were show in Fig.3&4. It was found that increase in the binding concentration, the decrease in the drug release. However, all the batches of the tablets were passed B.P. dissolution specification. CONCLUSION It can be conclude that Moringa oleifera gum can be used as binding agent in tablet formulations and may be substituted for more expensive binders. ACKNOWLEDGEMENT The authors are grateful to Principal, R.M.E.S s College of Pharmacy Gulbarga, for his valuable support and providing necessary facilities to carry out the research work. REFERENCES 1. King RE, Tablets in Remington s Pharmaceutical Sciences, 15 th Ed. Mack Pub. Coy. Easton, Pennnsylvania, 1975; 1587. 2. Gordon ER, Rosanke TW, Fonner OE, Anderson NR, Baker GS, In: Pharmaceutical Dosage Forms: Tablets Lieberman H.A., Ingram L., J.Pharm. Sci. 1972; (61): 457. 3. Nasipuri RN, Evaluation of Cocoyam Starch as Tablet Binder and Diintegrant Acta Pharm Helv. 1979; 54 (2): 48-53. 4. Tsige G, Alexander SN, Evaluation Starch Obtained From Esente Ventricosum As a Binder and Disintegrant For Compressed Tablets. J.Pharm. Pharmacol. 1993; 45(307): 317-320. 5. Iwuagwu MA, Evaluation of Some Soluble Starches a Lubricants in the Formulation of Compressed Tablet, World Pharm. J. 1991; 8(1): 19-23. 6. Ibezim EC, Ofoefule SI, Omeje EO, Onyishi VI, Odoh UE, The Role of Ginger Starch as a Binder in Acetaminophen Tablets. Scientific Research and Essay 2008; 3(2): 046-050. 7. Wealth of India-Raw Materials, New Delhi: Council of Scientific and Industrial Research. 1998; 2:429.

8. Oyi AR, Allagh TS and Olayemi OJ, Comparative Binding Effects of Wheat, rice and Maize starches in Chloroquine Phosphate Tablet Formulations. Research J. Applied Pharm. Sci., Engg and Tech. 2009; 1(2): 77-80. 9. Liberman HA, Lachman.L, Schwartz.JB, Wadke DA, Serajuddin, ATM, Preformulation testing in pharmaceutical Dosage Forms-Tablets. Marcel Dekker: Newyork, 1989; 55. 10. Schwartz JB, Martin ET and Deliner, Intragranular Starch: Compression of Starch USP and Modified Corn Starch. J. Pharm. Sci. 1975; 64:328-332. 11. British Pharmacopoeia. Majesty s Stationary Office, London, 2001; 1576 12. Well JI. Tablet testing. In: Swarbrick J, Boylan JC, editors. Encyclopedia of Pharmaceutical Technology, Vol. 14. New York: Marcel Dekker. 1997; 401-418. 13. Olayemi OJ, Oyi and Allagh TS, Comparative Evaluation of Maize, rice and wheat starch poders as pharmaceutical exciepients. Nig. J. Pharm. Sci. 2008; 7(1): 154-161. 14. Pilpel N, Otuyemi SO and Kurup TRR, Factors affecting the disintegration and dissolution of chloroquine phosphate/ starch tablets. J.Pharm. Pharmacol. 1978; 30:214. Table 1: Formulation of Chloroquine phosphate tablets Ingredients Formulation Code (mg) M1 P1 M2 P2 M3 P3 Chloroquine phosphate 250 250 250 250 250 250 Maize Starch (diluent) 23 23 17 17 11 11 Moringa oleifera gum 4 -- 6 -- 8 -- (%) Potato starch (%) -- 4 -- 6 -- 8 Aerosol 200 (%) 5 5 5 5 5 5 Talc (%) 0.5 0.5 0.5 0.5 0.5 0.5 Magnesium stearate (%) 0.5 0.5 0.5 0.5 0.5 0.5 Table 2: Pre compression parameters data for Chloroquine phosphate granules Parameters Moringa oleifera gum M1 M2 M3 Potato starch P1 P2 P3 Bulk density (gm/ml) 0.415 0.422 0.431 0.470 0.479 0.490 Tapped density (gm/ml) 0.462 0.471 0.485 0.515 0.523 0.544 Hausner s ratio 1.1132 1.1161 1.1252 1.0957 1.0918 1.1102 Carr s index (%) 10.1731 10.4033 11.1340 8.7378 8.4130 9.9264 Moisture content 3.0 3.2 3.0 3.5 3.0 3.5 Angle of repose (degrees) 23.52 23.18 22.70 24.13 23.23 22.15

Table 3: Post compression study of Chloroquine phosphate tablets Parameters Hardness (kg/cm 2 )* Friability (%)* Average weight variation (%)* Disintegration time(minutes)* Thickness (mm) Content uniformity(%)* Dissolution time (After 60 minutes)* Dissolution time (After 90 minutes)* Moringa oleifera gum M1 M2 M3 Potato starch P1 P2 P3 6.0±0.15 6.5±0.30 7.1±0.20 4.5±0.10 5.6±0.15 5.8±0.22 0.89±0.03 0.76±0.02 0.52±0.06 1.12±0.06 0.70±0.03 0.31±0.07 1.15 1.19 1.27 1.16 1.18 1.78 7.52±0.27 9.41±0.12 10.05±0.39 7.45±0.34 10.06±0.27 10.25±0.22 3.14 3.21 3.19 3.23 3.20 3.25 99.91±0.79 98.72±1.24 98.52±1.10 98.45±0.77 98.73±0.17 98.97±0.51 79.18±0.41 73.31±0.52 70.11±0.37 86.66±0.25 80.37±0.56 76.33±0.14 87.29±0.53 84.29±0.53 81.11±0.56 95.22±0.31 91.11±0.32 89.53±0.54 * All values are expressed as mean ±SD, n=3. Fig 1: Moringa oleifera Tree Fig 2: Moringa oleifera drumsticks

120 100 80 60 40 M1 M2 M3 Cumulative % drug release 20 0 0 20 40 60 80 100 120 Time (min) Fig 3: In-vitro dissolution profiles of Moringa oleifera gum formulations 100 80 60 40 P1 P2 P3 Cumulative % drug release 20 0 0 20 40 60 80 100 120 Time (min) Fig 4: In-vitro dissolution profiles of potato starch formulations. Source of support: Nil, Conflict of interest: None Declared