Research Article ISSN: 0974-6943 Bookya Padmaja et al. / Journal of Pharmacy Research 2015,9(2), Available online through www.jprsolutions.info Formulation and Evaluation of Fast Dissolving Tablets of Ranitidine Hydrochloride Bookya Padmaja 1 *, Raparla Ramakrishna 1, Goutham Goud 2 1 Department of Pharmaceutics, Vaageswari Institute of Pharmaceutical Sciences, Karimnagar, 505481, Telangana, India 2 Department of Pharmaceutics, Vaageswari College of Pharmacy, Karimnagar, 505481, Telangana, India. Received on:21-12-2014; Revised on: 23-01-2015; Accepted on:28-02-2015 ABSTRACT Aim: The present work fast dissolving tablets of Ranitidine Hydrochloride were designed with a view to provide quick onset of action. Ranitidine Hydrochloride which is a histamine H2-receptor antagonist belongs to class III of Biopharmaceutical classification system. Methods: Fast dissolving tablets were prepared by direct compression method by using various super disintegrants like kollidon, croscarmellose sodium, kyron and sodium starch glycolate. Results: The powder blend was evaluated for pre-compression parameters in order to assess the flow properties of powder like bulk density, tapped density, compressibility index, hausner s ratio, angle of repose. The powder blend showed excellent flow properties. The prepared tablets were evaluated for thickness, hardness, friability, disintegration time and in vitro dissolution studies for a period of 1 hour. Conclusion: Among all prepared tablets the (F -5) formulation containing kollidon 12.5 % w/w were emerged as the best formulation and the in vitro drug release was found to be within 30 min compared to all superdisintegrants. KEYWORDS: Direct compression, Fast dissolving tablets, Ranitidine hydrochloride, Superdisintegrants. 1. INTRODUCTION In the present study- research novel drug delivery systems are developed for expanding markets / indications, extending product life cycles and generating opportunities. Oral administration is the most popular route for systemic effects due to its ease of ingestion, pain, avoidance, versatility and most importantly patient compliance. In these solid formulations they do not require any sterile conditions and are therefore, less expensive to manufacture. Patient compliance, high-precision, dosing and manufacturing efficiency make these tablets as the solid dosage form of choice 1. Ranitidine is a histamine H2-receptor antagonist. An H2-receptor antagonist drug used to block the action of histamine on parietal cells in the stomach, decreasing acid production by these cells. The H2 antagonists are competitive inhibitors of histamine at the parietal cell H2 receptor. They suppress the normal secretion of acid by parietal cells and the meal-stimulated secretion of acid. The drug is 50% absorbed orally but it undergoes hepatic metabolism. Ranitidine is used in treatment of peptic ulcers. Thus, Ranitidine is better option for the development of an immediate release tablets 2. The purpose of this study *Corresponding author. Bookya Padmaja Department of Pharmaceutics, Vaageswari Institute of Pharmaceutical Sciences, Karimnagar, 505481, Telangana, India was to develop and characterize immediate release tablets of Ranitidine hydrochloride by using various super disintegrants such as croscarmellose sodium, kollidon, kyron, sodium starch glycolate which disintegrates rapidly and get dissolved to release the medicaments. This helps in immediate release of medicament, leading to an increase in bioavailability of the drug and quick onset of pharmacological action can take place. 2. MATERIALS Ranitidine hydrochloride was obtained as gift sample from Aurabindo Labs, Hyderabad, India. Croscarmellose sodium, kollidon, kyron, sodium starch glycolate, lactose were obtained from Nihal Traders Pvt. Ltd, Mumbai. All others chemicals like magnesium stearate and talc were received from SD Fine chemicals, Mumbai. 3. METHODS 3.1. Preparation of fast dissolving tablets by direct compression method Fast dissolving tablets of Ranitidine hydrochloride were prepared by using direct compression method. The composition of various formulations of the tablets with their codes is listed in Table 1. All the materials were passed through 80 # screens prior to mixing. Ranitidine hydrochloride, microcrystalline cellulose, Kollidon, crosscarmellose
Bookya Padmaja et al. / Journal of Pharmacy Research 2015,9(2), Table 1. Formulation of Ranitidine hydrochloride fast dissolving tablets Ingredients (mg / tablet) F1 F2 F3 F4 F5 F6 F7 F8 F9 F10 Ranitidine Hydrochloride 168 168 168 168 168 168 168 168 168 168 Microcrystalline cellulose 50 50 50 50 50 50 50 50 50 50 Sodium starch glycolate 10 15 20 Kollidon 7.5 12.5 Crosscarmellose sodium 5 7.5 Kyron 1.25 5 10 Lactose 19.5 14.5 9.5 22 17 24.5 22 28.25 24.5 19.5 Magnesium stearate 1.25 1.25 1.25 1.25 1.25 1.25 1.25 1.25 1.25 1.25 Talc 1.25 1.25 1.25 1.25 1.25 1.25 1.25 1.25 1.25 1.25 Total weight of tablet (mg) 250 250 250 250 250 250 250 250 250 250 sodium, sodium starch glycolate (SSG), kyron, lactose, magnesium stearate,talc were mixed using a glass mortar and pestle 3. All the materials were directly compressible so this uniformly mixed blend was compressed into tablets of 250 mg weight on 12 station tablet compression machine (Saimach machineries, India) using 12 mm flat round punches. 3.2. Evaluation of powder blends of Ranitidine hydrochloride formulations The powder blends of Ranitidine hydrochloride formulations were evaluated before compression to assess the flow properties of the powder 4, 5. 3.2.1. Determination of bulk density and tapped density The bulk density is ratio of the weight of the powder and volume it occupies. It is expressed as gm/ml. An accurately weighed quantity of the powder blend (W), was carefully poured into the graduated cylinder and the volume (V O ) was measured. Then the graduated cylinder was closed with lid. The bulk density apparatus (Electro Lab, Mumbai) was set for 100 tappings and after tappings the volume (V F ) was measured and continued until the consecutive readings were equal. The bulk density, and tapped density were calculated using the following formula. Bulk density (B.D) = W / V O Tapped density (T.D) = W / V F Where: W = weight of the powder V O = initial volume, V F = final volume Where T.D and B.D are tapped density and bulk density respectively. 3.2.3. Hausner s ratio This is an indirect index of ease of powder flow. It was calculated by the following formula. The correlation of hausner s ratio with flow properties of powder was given in Table 2. Tapped Density Hausner s Ratio =... Bulk Density 3.2.4. Angle of repose It is the maximum angle possible between the surface pile of powder and horizontal plane. The frictional forces in the loose powder can be measured by angle of repose. The tangent of angle of repose is equal to the coefficient friction (µ) between the particles. Hence the rougher and more irregular the surface of particles the greater will be angle of repose.? = tan -1 h/r Where? = angle of repose, h = height of the pile, r = radius of the pile The correlation of angle of repose with flow properties of powder was given in the Table 2. Table 2. Evaluation data of pre-compression studies Batch Angle of Bulk Tapped Compressibility Hausner s No repose (q) density density index ratio (g/ml) (g/ml) (%) 3.2.2. Compressibility index The compressibility index is indirectly related to flow rate, cohesiveness and particle size of the powder. The compressibility index of material is estimated by tapped and bulk density of powder. The correlation of compressibility index of powder was given in Table 2. % Compressibility index = [(T.D B.D) / T.D] *100 F1 27.35 ±0.03 0.48 ± 0.02 0.56±0.03 14.2 ± 0.05 1.16 ± 0.02 F2 26.52 ±0.05 0.42 ± 0.03 0.48±0.04 12.5 ±0.03 1.14 ±0.04 F3 27.86 ±0.07 0.49 ± 0.05 0.56±0.02 14.1 ±0.05 1.14 ±0.07 F4 25.61 ±0.06 0.52 ±0.04 0.60 ±0.05 15.3 ±0.04 1.15 ±0.05 F5 26.45±0.04 0.47 ±0.06 0.54 ±0.04 14.8 ±0.05 1.14±0.06 F6 28.21 ±0.05 0.54±0.07 0.61 ±0.06 12.9 ±0.03 1.12 ±0.04 F7 27.35 ±0.04 0.51±0.04 0.58±0.04 13.7 ±0.06 1.13 ±0.05 F8 26.34 ±0.07 0.48 ±0.05 0.56 ±0.05 14.5 ±0.08 1.16 ±0.04 F9 28.64 ±0.05 0.45 ±0.04 0.52 ±0.04 13.4 ±0.05 1.15 ±0.05 F10 27.45 ±0.04 0.43 ±0.06 0.49 ±0.05 13.9 ±0.04 1.13 ±0.03
R = {W a W b /W b } 100 Bookya Padmaja et al. / Journal of Pharmacy Research 2015,9(2), 3.3. Evaluation of Ranitidine hydrochloride fast dissolving tablets 3.3.1. Weight variation Twenty tablets were randomly selected from each batch and their weight was determined individually and collectively on a digital weighing balance. The average weight of the tablet was determined from the collective weights 6. 3.3.2. Thickness Ten tablets from each formulation were taken randomly and their thickness was measured using a Vernier callipers and the reading was recorded in millimeters 7. 3.3.3. Hardness or Crushing strength Test The force required to break the tablet is measured in kilograms. Hardness of the tablet was determined using the Monsanto hardness tester. Three tablets from each formulation batch were tested randomly and the average reading was noted 7. 3.3.4. Friability Five tablets were weighed and the initial weight of these tablets was recorded and placed in Roche friabilator and rotated at the speed of 25 rpm for 100 revolutions. Then tablets were removed from the friabilator, dusted off the fines and again weighed and the weight was recorded. Percentage friability was calculated by using the formula 8 : F= Initial weight - Final weight / Initial weight * 100 3.3.5. 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. Where W b and W a are the weights before and after water absorption, respectively. 3.3.6. Wetting Time A piece of tissue paper (12cm x10.75cm) folded twice was placed in a small Petri dish (ID = 9 cm) containing 6ml of purified water. A tablet was placed on the paper and the time taken for complete wetting was noted. Three tablets from each formulation were randomly selected and the average wetting time was noted 9. 3.3.7. Disintegration time The in vitro disintegration time was determined using disintegration test apparatus. A tablet was placed in each of six tubes of apparatus and one disc was added to each tube. The time in seconds taken for complete disintegration of tablet with no palpable mass remaining in apparatus was measured in seconds 10. 3.3.8. Content uniformity of tablets The drug content was determined by taking the powder equivalent to 10 mg, then it was dissolved in the distilled water and absorbance was taken against 313.5 nm using a UV-Visible double beam spectrophotometer 11 (UV-1700 Shimadzu). 3.3.9. In-vitro dissolution testing In-vitro dissolution study of Ranitidine hydrochloride was carried using Type II (Paddle) (Electrolab TDL-08L) (Mumbai) dissolution test apparatus. The dissolution test was performed using 900 ml of 0.1 N HCl as the dissolution media at 50 rpm at 37 C ± 5 C. Samples of 5 ml were withdrawn at predetermined time intervals, filtered and replaced with 5 ml of fresh dissolution medium. The collected samples were determined spectrophotometrically at 313.5 nm. All the dissolution tests were carried out in triplicates 12. 1. RESULTS AND DISCUSSION The objective of the present study was to prepare fast dissolving tablets of Ranitidine hydrochloride to enhance patient compliance and quick onset of action by using different concentrations of superdisintegrants and to optimize the best superdisintegrant. The formulae required to prepare fast dissolving tablets was given in the Table1. The powder blends of different fast dissolving formulations were evaluated for various parameters such as angle of repose, bulk density, tapped density, compressibilty index and Hausner s ratio. The values were given in Table 2 and were within the official limits with less standard deviation. The value of angle of repose (? < 30) indicates that the powder had good flow properties. The results of compressibility index values up to 15% indicates good to excellent flow properties. The results of Hausner s ratio values ranged between 1.00 to 1.18 considered as good to excellent flow properties. The results of loose bulk density and tapped bulk density ranged from 0.42 to 0.54 and 0.48 to 0.58 respectively. All these results indicated that the powders possessed excellent flow properties. The fast dissolving tablets (F1 F10) were subjected to various tests such as weight variation, thickness, hardness, friability, disintegration and drug content and the results were shown in the Table 3. All the tablets compiled with the pharmacopeia specifications for these tests. The in-vitro dissolution studies of fast dissolving tablets were conducted in simulated gastric fluid 0.1 N HCl for 1 hour. The dissolution
Bookya Padmaja et al. / Journal of Pharmacy Research 2015,9(2), Table 3. Evaluation data of post compression studies Batch Weight Hardness Thickness Friability Disintegration Drug Water Wetting No variation (kg/cm 2 ) c (mm) b (%) d time (min) c Content absorption time (mg) a (%) c ratio (%) c (sec) c F1 249 ±0.3 2.5±0.3 3.59±0.5 0.51±0.04 3min 19 Sec 99.7 ± 0.4 85.2 ± 0.4 98.4 ± 0.4 F2 250±0.5 2.6±0.5 3.61±0.7 0.39±0.06 3 min15 Sec 100.2 ±0.7 94.2 ± 0.9 97.3 ± 0.6 F3 248±0.4 2.5±0.4 3.58±0.5 0.52±0.04 3 min11 Sec 98.6 ±0.6 65.4± 1.2 97.9 ± 0.5 F4 249±0.3 2.7±0.5 3.59±0.6 0.46±0.05 2 min 35 Sec 98.3 ±0.4 74.1 ± 1.3 96.5 ± 0.2 F5 251±0.7 2.6±0.5 3.60±0.4 0.49±0.04 1 min 29 Sec 99.4 ±0.3 61.9 ± 0.6 97.1 ± 0.4 F6 248±0.5 2.5±0.7 3.59±0.7 0.55±0.07 3 min 12 Sec 97.3 ±0.4 70.4 ± 0.4 97.5 ± 0.7 F7 249±0.6 2.5±0.5 3.60±0.5 0.48±0.05 3 min 9 Sec 99.3 ±0.6 57.1 ± 0.5 96.9± 0.7 F8 250±0.5 2.6±0.4 3.60±0.6 0.46±0.04 3 min 25 Sec 98.5 ±0.8 69.3 ± 0.6 98.7 ± 0.3 F9 249±0.7 2.7±0.5 3.60±0.7 0.38±0.06 3 min 18 Sec 91.2 ± 0.7 81.1 ± 0.2 97.6 ±0.5 F10 251±0.6 2.6±0.3 3.61±0.5 0.51±0.05 3 min 13 Sec 98.3 ± 0.5 90.1 ± 0.4 96.1 ± 0.3 a Data presented as mean ± SD n =20 b Data presented as mean ± SD n =10 c Data presented as mean ± SD n =3 d Data presented as mean ± SD n =5 Table 4. Evaluation data of In-vitro drug release Time % Cumulative drug release c (Min) F1 F2 F3 F4 F5 F6 F7 F8 F9 F10 0 0 0 0 0 0 0 0 0 0 0 5 33.1 36.2 39.2 48 59.2 33.1 37.2 32.1 35.1 39.4 10 49.4 51.6 53.4 65.4 78.3 47.2 52.4 47.8 50.2 49.2 15 64.8 66.7 69.5 84.5 94.5 63.8 67.4 62.7 64.8 61.2 30 83.2 85.1 86.2 97.4 99.6 82.3 86.8 81.8 83.9 79.9 45 95.8 97.3 98.4 99.7-94.5 97.5 94.3 95.8 91.2 60 99.2 99.5 99.8 - - 99.1 99.5 99.1 99.3 99.6 c Data presented as mean ± SD n =3 Table 5. Comparison of best dissolution profiles of Ranitidine hydrochloride tablets with various super disintegrants Time % Cumulative drug release c (min) Sodium Kollidon Cross Kyron Starch (F5) carmellose (F10) Glycolate (F7) (F3) 0 0 ±0.0 0 ±0.0 0 ±0.0 0 ±0.4 5 39.2 ±0.5 59.2 ±0.4 37.1 ±0.4 39.6 ±0.4 10 53.4 ±0.7 78.4 ±0.5 52.5 ±0.5 49.2 ±0.5 15 69.5 ±0.3 94.2 ±0.3 67.4 ±0.7 69.9 ±0.4 30 86.2 ±0.5 99.6 ±0.4 86.2 ±0.8 87.9 ±0.7 45 98.4 ±0.3-97.1 ±0.6 98.2 ±0.6 60 99.8 ±0.4-99.4 ±0.5 99.6 ±0.7 Fig. 1: In-vitro dissolution profiles of formulations F1- F5 Fig. 3: Comparision of best dissolution profile of Ranitidine hydrochloride with various disintegrants studies release data of different superdisintegrants like Sodium starch glycolate (F1, F2, F3), Kollidon (F4, F5), Croscarmellose (F6, F7), Kyron (F8, F9, F10) were shown in the Table 4 and in the Fig. 1 and 2. The drug release from F1, F2 & F3 composed of Sodium starch glycolate 2%, 4% and 8 % was found to be 99.2, 99.5 and 99.8 in 60 min. The drug release form formulations F4 and F5 which were formulated with Kollidon were found to be 99.7 (45 min) and 99.6 (30 min). The drug Fig. 2: In-vitro dissolution profiles of formulations F6 F10 release form formulations F6 and F7 which were composed of
Bookya Padmaja et al. / Journal of Pharmacy Research 2015,9(2), Croscarmellose were found to be 99.1 and 99.5 in 60 min. The drug release from the formulations F8, F9 and F10 which were formulated with Kyron was found to be 99.1, 99.3, and 99.6 in 60 min. Finally comparison of all formulations was given in the Table 5 and Fig. 3. 5. CONCLUSION The present study was carried out to develop the fast dissolving tablets of Ranitidine hydrochloride by using various superdisintegrants at different ratios. The formulation prepared with kollidon (F 5) in a concentration of 12.5 % w/w for fast dissolving tablets was found to be more suitable than the formulation prepared with other superdisintegrants. It was found that the release rate was found to be influenced by the nature of the superdisintegrant and the concentration of the disintegrant employed in the preparation of the tablets. Conflicts of interest All authors have none to declare. ACKNOWLEDGEMENTS The authors are thankful to Aurobindo Pharmaceuticals, Hyderabad for providing Ranitidine hydrochloride as gift sample. The authors are thankful to management Dr. G. Srinivas Reddy, Karimnagar, India of Vaageswari educational society for providing the necessary facilities to carry out this research work. 6. REFERENCES 1. Nyol Sandeep, Dr. M.M. Gupta. Immediate Drug Release Dosage Form: A Review. J of Drug Delivery and Therapeutics. 2013: 3(2): 155-161. 2. Sachin Sharma, Jitendra Kumar, Arun Arya, Amrish Chandra, Pankaj Jaiswal. Formulation and Evaluation of Mouth Dissolving Tablets of Ranitidine HCl. Int. J. of Pharm Tech Res. 2010: 2 (2): 1574-1577, April-June. 3. Parmar R.B, Baria A. H, Tank H.M. Formulation and Evalua- Source of support: Nil, Conflict of interest: None Declared tion of Domperidone Fast Dissolving Tablets. Int. J. of Pharm Tech Res. 2009: 1(3): 483-487, July-Sept. 4. Subrahmanyam CVS. Text book of Physical Pharmaceutics. 2nd ed. New Delhi: Vallabh Prakashan. 2005; 210-228. 5. Lachman L, Lieberman A, Kinig JL. The Theory and practice of Industrial Pharmacy. 2nd ed.varghese Publishing House: 1999; 67-74. 6. Ravi Subhashini, Ramesh Reddy D. Formulation and Evaluation of Domperidone Fast Dissolving Tablets Using Plantago Ovata Mucilage. Int. J. of Pharm Tech Res. 2013: 4(9): Sept. 7. M. Jhansi rani, A. Surendra.M.S. Sudhakar Babu. Formulation and Evaluation of Domperidone Fast Dissolving Tablets using Natural Superdisintegrants. Int. J. of Res in Pharm and Nano sci. 2013: 2 (2): 152-157. 8. Mahanthesha. M.K, T.S. Nagaraja, Lakshmi Radhika.G, Anand B Geni. Formulation and Evaluation of Mouth Dissolving Tablets of antibacterial agent. Int. J. of advanced Res. 2013: 1 (6): 465-470 9. Devendra Revanand.R, Hemant Narhar.G, Vikas Vasant. P, Vinod Madhaorao. T, Vijay Raghunath.P. Formulation and Evaluation of Fast Dissolving tablet of Albendazole. Int. Current Pharm J. 2012: 1(10): 311-316. 10. Shaikh T.H,Bhise S.D, Ligade D.M, Patil M.V.K. Formulation and evaluation of mouth dissolving tablet of Metformin HCl. Int. Res J. of Pharm. 2012: 3(6) : 96-98. 11. Prameela Rani A, Archana N, Siva Teja P, Mohan Vikas P, M. Sudheer Kumar.Formulation and Evaluation of Orodispersible Metformin tablets: a comparative study on Isphagula husk and crosspovidone as superdisintegrants. Int. J. of Applied Pharma. 2010:2 (3), 15-21. 12. Shailaja CJ, Preeti Karwa, Nargund LVG, Laxman SV. Development of Fast Dissolving tablets of Losartan potassium using Kollidon CL-SF. J of Chem and Pharm Res. 2013: 5 (5):119-127.