Formulation and Evaluation of Floating Tablets of Ranitidine Hydrochloride with Liquorice as Natural Ulcer Protective Agent

Abstract

The concurrent trend in pharmaceutical evolution accentuates the effectiveness of floating tablets over conventional dosage form. Furthermore, it facilitates site-specificity, controlled release and is irrespective of gastric emptying. The present study was carried out to enhance the bioavailability of Ranitidine HCl, a floating dosage form with controlled release. Ranitidine HCl has a narrow absorption window in the gastrointestinal tract; therefore its absorption was improved by modifying the dosage form. The action potential of a drug is synergized by combining it with a natural ulcer protective agent that is liquorice. The tablets were prepared by wet granulation method. The batches were formulated using a different ratio of HPMC K15 and Carbopol. It ensures the effectiveness of the formulation variable on drug release and buoyancy property of the delivery system. The prepared formulations show significant results obtained by pharmacopoeial quality control tests. In-vitro dissolution study was also performed to check whether the ratio of polymers was optimum for controlled release or not. The present study suggests that the Ranitidine HCl and liquorice together are well compatible with each other. However, the effectiveness of the drug combination partially depends upon the ratio of polymers. Poonam Sansarwal, Sunaina Sharma, Richa Ohri 1. Himalayan Institute of Pharmacy, Kala-amb, Himachal Pradesh, India-173030 2. LBR college of Pharmacy, Panchkula, Haryana, India-134109 Submission: 23 November 2019 Accepted: 29 November 2019 Published: 30 December 2019 www.ijppr.humanjournals.com Citation: Richa Ohri et al. Ijppr.Human, 2019; Vol. 17 (1): 38-59. 39 INTRODUCTION Most of the medicaments are administered by oral route due to high patient compliance. However, the ideal drug delivery system needs two basic components. Firstly, the drug should be delivered at a predetermined rate for a prolonged time, for the prevention of fluctuation in plasma concentration. Secondly, the drug should bind solely to its selective receptor. Unfortunately, available systems do not relay such kind of properties. Hence the time demands modification in conventional dosage form for the betterment of therapeutic efficacy and drug safety [1, 2]. Manufacturing sustained release or controlled release drug delivery systems can help overcome the above-mentioned drawbacks. For instance, the major risk factor is decreased bioavailability due to the narrow absorption window. So far several new approaches such as bioadhesive, floating, swelling-activated drug delivery systems were made to lengthen the Gastric Retention Time (GRT)[3]. The existing trend in pharmaceutical evolution accentuates the effectiveness of floating tablets over conventional dosage form. On inference, it facilitates site-specificity, controlled release and is irrespective of gastric emptying[4, 5].Floating tablet tending to keep afloat for several hours. The buoyancy of tablets is achieved by gas generating agents that liberates carbon dioxide when came in contact with gastric fluid. Besides this, acidic pH assists entrapment of released CO2 in hydrocolloid gel that maintains extended floatation over long duration. There may be uncertain emptying of the floating system by settling in the stomach due to initial high density which goes down with time. on this emphasis floating system require an adequate amount of gastric fluid for tablet buoyancy[6]. The present study deals with the development of floating tablets of Ranitidine HCl in combination with natural ulcer protective agent that is liquorice. Ranitidine HCl abates acid secretion in the stomach by blocking histamine receptor H2. Liquorice is found to be effective in the treatment of gastric ulcers due to the antiulcer and anti-inflammatory properties of glycyrrhetinic acid[7, 8]. Liquorice elevates prostaglandin concentration in the digestive system that assists mucous secretion. Also, the antipepsin effect of liquorice perpetuates the life span of surface cells in the stomach[9]. www.ijppr.humanjournals.com Citation: Richa Ohri et al. Ijppr.Human, 2019; Vol. 17 (1): 38-59. 40 MATERIALS AND METHODS: MATERIALS: Ranitidine HCl(received as a gift sample from ZEE Labs Paonta Sahib, H.P ), Liquorice(extracted received as a gift sample from Konark herbal and health care, Kala Amb, H.P), Citric acid, Sodium bicarbonate, Carbopol, HPMC K15, Talc, Magnesium stearate, Ethanol, Hydrochloric acid, Sodium hydroxide, Potassium hydrogen diphosphate (SD fine chemicals). METHODS Construction of Calibration Curve: Preparation of simulated gastric fluid (SGF)[10] 2 g of sodium chloride was dissolved in 500 ml deionized water, followed by adding 7 ml of concentrated HCl and final volume made up to 1000 ml with water. The pH of the solution was adjusted to 1.2 with 0.1N HCl. Preparation of sample solutions of Ranitidine HCl The primary stock solution was prepared by dissolving 112 mg of pure Ranitidine HCl equivalent to 100 mg in 100ml SGF pH 1.2 to get a concentration of 1mg/ml. Secondary stock solution 5ml was pipetted out from the primary stock solution and transferred into 50 ml volumetric flask, the final volume was made up to 50 ml using SGF pH 1.2 Further sample solution of concentration 20 μg/ml, 40 μg/ml, 60 μg/ml, 80 μg/ml, 100 μg/ml were prepared from secondary stock solution. The absorbance was measured at 314 nm by UV spectrophotometer (Labindia Analytical) using SGF pH 1.2 as a blank solution. The calibration curve was plotted against concentration (x-axis) and absorbance (y-axis). Compatibility studies: Were performed by FT-IR of drug liquorice and polymers, and then interpretation was done to check compatibility. www.ijppr.humanjournals.com Citation: Richa Ohri et al. Ijppr.Human, 2019; Vol. 17 (1): 38-59. 41 Formulation of tablet by wet granulation method: Accurate quantity of Ranitidine HCl, liquorice were weighed and separately passed through a sieve of mesh size 40#, then mixed well. After those polymers i.e. HPMC K15 and Carbopol were mixed in required quantity to the mixture of drugs. Then added the sodium bicarbonate and citric acid in the mixture and mix well, these act as effervescent agents that maintain the floating properties of tablets. Wet mass of mixture was made with the help of 95% ethanol (granulating agent) and wet screening was done through a sieve with mesh aperture 10#. Drying of granules was done in a hot air oven at 40°C using a tray drying technique. Dry granules are sifted through a sieve with mesh aperture 40#, and about 15 % of the fine is allowed to remain in the granules. Finally, the dried granules are blended along with magnesium stearate and talc in an octagonal blender. Then the blend was compressed using a caimach compression machine. Table No. 1: Composition of one tablet for different batches Batch code Composition (Qty in mg) F1 F2 F3 F4 F5 Ranitidine HCl 168 168 168 168 168 Liquorice 50 50 50 50 HPMC K15 25 50 50 50 10 Carbopol 50 25 50 10 50 Citric acid 10 10 10 10 10 Sodium bicarbonate 50 60 70 80 90 Talc 5 5 5 5 5 Magnesium stearate 7 7 7 7 7 Pre-compression evaluation:[11, 12] 1. Bulk density and tapped density 2. Angle of repose 3. Compressibility index 4. Hausner’s ratio www.ijppr.humanjournals.com Citation: Richa Ohri et al. Ijppr.Human, 2019; Vol. 17 (1): 38-59. 42 Bulk density: 20 gm of granules were weighed and poured in measuring cylinder, bulk volume was measured. Bulk density was calculated using the formula: Bulk density = (mass of granules/bulk volume) x100 Tapped density: The measuring cylinder was tapped to get constant volume, followed by calculating tapped density using the expression: Tapped density= (mass of granules/tapped volume of granules) x100 The angle of repose (): a heap of the blend was formed using a funnel, followed by measuring height and radius of it. tan  = h/r  = tan (h/r) Where  = angle of repose h = height of heap of blend r = radius of a heap of blend Compressibility index & Hausner’s ratio: were determined by substituting the value of bulk density and tapped density in the formula: Compressibility index = (Tapped density-bulk density/Tapped density) x100 Hausner’s ratio= Tapped density/bulk density Evaluation of tablets: The prepared tablets were evaluated based on following parameters: www.ijppr.humanjournals.com Citation: Richa Ohri et al. Ijppr.Human, 2019; Vol. 17 (1): 38-59. 43 Physicochemical evaluation of floating tablets [13-15] Weight variation Twenty tablets were taken from the lot and their weight was measured followed by average weight. Then deviations from the average weight were calculated and compared with an IP 2014 limit of weight variation. Diameter and thickness: They were measured with the help of Vernier calliper. Friability: Roche friabilator was used to determine the friability. 20 tablets were selected and weighed (Winitial) and transferred to the friabilator. The friabilator was rotated at 25 rpm for 4 minutes. Then final weights of tablets were observed i.e. Wfinal. Percentage of friability was calculated using an expression: % Friability = (Winitial -Wfinal / Winitial) × 100 Hardness: Monsanto hardness tester was used to determine the hardness of tablets (Kg/cm). Swelling index: It was determined by keeping tablets in simulated gastric fluid. The swollen weight of tablets was observed at different time intervals. Then the swelling index was calculated using the formula: Swelling index= (wet weight-dry weight/dry weight) X100 In-vitro buoyancy study: Floating lag time and total floating time was evaluated for all batches of Ranitidine HCl. To determine floating lag time a tablet was selected randomly from each batch and kept in 100 ml beaker containing simulated gastric fluid (pH 1.2). Floating lag time was the time taken by each tablet to rise and float on the surface of a fluid. www.ijppr.humanjournals.com Citation: Richa Ohri et al. Ijppr.Human, 2019; Vol. 17 (1): 38-59. 44 The dissolution apparatus USP type I