Testing Drug Content of Famotidine Core Tablets

Testing Drug Content of Famotidine Core Tablets 6. Formulation development and evaluation 6.1 Preparation of core tablets Core tablets of famotidine were prepared by direct compression and batch size was kept as 100 tablets. Drug , sodium chloride, polymer and MCC were co-sifted through sieve # 30 Now the blend is mixed in polybag for 10 min Citric acid was crushed using mortar and pestle and sifted through sieve # 60 And this is added to above blend and mixed in a polybag for 10 min. Then magnesium stearate talc were passed through sieve #60 and to the above blend and mixing continued for another 2 min Now the blend is compressed to tablets having the average weight of 180 mg using 8 mm round concave punch and at low relative humidity 20 % RH 6.2 Coating of core tablets: 6.2.1. Preparation of coating solution: 5 ml of water was taken in a beaker and to this required amount of PEG 400 was added and dissolved 95 ml of acetone was taken in a beaker and stirred at 150 rpm using electrical stirrer to this above solution was added and stirred for 5 min Now to the above solution 5 gm of cellulose acetate was added slowly and stirring is continued for another 30 min i.e until a clear solution was formed. 6.2.2. Procedure for coating of semi permeable membrane: Coating was done using RD Lab Coater. Core tablets were placed in the coating pan and coated with cellulose acetate solution coating parameters are maintained as below: Inlet temperature : 40 oC  ± 2 oC Bed temperature: 35 oC rpm of pan: 15 -17 Spray rate: 3-7 ml/min Atomizing air pressure: 2.0 psi Coating was done until required weight gain was achieved Drilling of orifice: The orifice was made using needles of different sizes i.e, 24, 22 guage INGREDIENTS F1 F2 F3 F4 F5 F6 Core tablet mg/tablet Famotidine 40 40 40 40 40 40 Citric acid 20 20 20 20 20 20 Sodium chloride 50 50 50 50 50 50 HPMC k100M 9 18 Polyox1105 7.2 Polyox 301 7.2 Polyox303 7.2 Sodium lauryl sulphate 3.6 3.6 3.6 3.6 3.6 3.6 Magnesium stearate 1.8 1.8 1.8 1.8 1.8 1.8 Talc 3.6 3.6 3.6 3.6 3.6 3.6 Avicel PH 102 43 43 53.8 53.8 53.8 53.8 Total wt of tablet 180 180 180 180 180 180 Coating solution Cellulose acetate 5 gm 15 % w/w of total solids (0.669 ml) 4 ml Upto 100 ml 4% PEG 400 Water Acetone Weight gain Coated tablets were left over night for drying Table 6.8 Formulation trails for optimum polymer (using various grades of HPMC and PEO) Table6.9 Formulation trails for optimum polymer concentration and coating weight gain INGREDIENTS F7 F8 F9 Core tablet mg/tablet Famotidine 40 40 40 Citric acid 20 20 20 Sodium chloride 50 50 50 Polyox 301 10.8 10.8 10.8 Avicel PH 102 50.8 50.8 50.8 Sodium lauryl sulphate 3.6 3.6 3.6 Magnesium stearate 1.8 1.8 1.8 Talc 3.6 3.6 3.6 Total wt of tablet 180 180 180 Coating solution Cellulose acetate 5 gm PEG 400 15 % w/w of total solids (0.669 ml) Water 4 ml Acetone Upto 100 ml Weight gain 4 % 3 % 5 % Table 6.10 Formulation trails of optimum plasticizer concentration INGREDIENTS F 10 F 11 F 12 Core tablet mg/tablet Famotidine 40 40 40 Citric acid 20 20 20 Sodium chloride 50 50 50 Polyox 301 10.8 10.8 10.8 Avicel pH 102 50.8 50.8 50.8 Sodium lauryl sulphate 3.6 3.6 3.6 Magnesium stearate 1.8 1.8 1.8 Talc 3.6 3.6 3.6 Total wt of tablet 180 180 180 Coating solution Cellulose acetate 5 gm 5 gm 5 gm PEG 400 (% w/w of total solids) 20% (0.89 ml) 25% (1.25 ml) 35% (1.4 ml) Water 4 ml 4 ml 4 ml Acetone Upto 100 ml Upto 100 ml Upto 100 ml Weight gain 4% 4% 4% 6.3 Evaluation of blend 6.3.1 Angle of repose Angle of repose: Weighed quantity of the drug was passed through a funnel kept at a height 2 cm from the base. The powder is passed till it forms a heap and touches the tip of the funnel. The radius the base of the conical pile, and the height of pile were measured and the angle of repose was calculated using the formula: (h/r) h = height of the pile r = radius of the base of the conical pile Table 6.4 Flow property and corresponding angle of repose Flow property Angle of repose (ÆÅ ¸) Excellent 25 – 30 Good 31 – 35 Fair-no need of aid 36 – 40 Passable –hang up chances 41 – 45 Poor – must vibrate, agitate 46 – 55 Very poor 56 – 65 Very, very poor >66 Formulation code Angle of repose F1 25.45 F2 22.92 F3 23.13 F4 19.20 F5 18.62 F6 17.20 F7 20.09 Table no. : Data for angle of repose of all formulations 6.3.2 Bulk density An accurately weighed quantity of powder carefully poured into graduated cylinder. Then after pouring the powder into the graduated cylinder the powder bed was made uniform without disturbing. Then the volume was measured directly from the graduation marks on the cylinder as ml. The volume measure was called as the bulk volume and the bulk density is calculated by following formula: Bulk density = Weight of powder / Bulk volume Tapped Density: After measuring the bulk volume the same measuring cylinder was set into tap density apparatus. The tap density apparatus was set to 300 taps drop per minute and operated for 500 taps. Volume was noted as (Va) and again tapped for 750 times and volume was noted as (Vb). If the difference between Va and Vb not greater than 2% then Vb is consider as final tapped volume. The tapped density is calculated by the following formula: Tapped density = Weight of powder / Tapped volume Compressibility Index: It gives the flow property of the granules. More is the compressibility; less will be the flow property. It was calculated by the following formula using previously obtained bulk and tapped densities. Carrs index = Tapped density Bulk density X 100 Tapped Density Hausner Ratio: It is used for flow property of the granules. It was also calculated from bulk and tapped densities using following formula: Hausners ratio = Tapped density / Bulk density Table 6.3 Flow property and corresponding Carrs index Hausner ratio Flow property C.I ( % ) Hausner ratio Excellent ≠¤10 1.00 – 1.11 Good 11 – 15 1.12 – 1.18 Fair 16 – 20 1.19 – 1.25 Passable 21 – 25 1.26 – 1.34 Poor 26 – 31 1.35 – 1.45 Very poor 32 – 37 1.46 – 1.59 Very, very poor >38 >1.60 Formulation code Bulk density (gm/cm3) Tapped density (gm/cm3) Carr’s index (%) Haussners ratio Angle of repose F1 0.486 0.631 22.9 1.25 25.45 F2 0.410 0.513 20.08 1.25 22.92 F3 0.438 0.601 18.259 1.18 23.13 F4 0.436 0.583 16.39 1.196 19.20 F5 0.430 0.520 17.31 1.21 18.62 F6 0.462 0.535 13.64 1.16 17.20 F7 0.446 0.523 14.72 1.17 20.09 Table no. : Data for Bulk density, Tapped density, Compressibility index and Hausner’s ratio of all formulations 6.4 Post compression studies 6.4.1 Weight variation The average weight of core tablets and coated tablets were determined using a digital weighing balance. 20 tablets were selected randomly from each batch and weighed individually, calculating the average weight and comparing the individual tablet weight to the average. From this, percentage weight difference was calculated. Table 6.11 Limits of weight variation IP/BP Limit USP 80 mg or less 10% 130mg or less More than 80mg or Less than 250mg 7.5% 130mg to 324mg 250mg or more 5% More than 324mg Table no. : Data for weight variation test of all formulations Formulation Code Avg weight (mean ±%deviation) Before Coating After Coating F1 178.42 ± 1.02 185.72 ±1.12 F2 181.31 ± 0.91 188.79 ±1.45 F3 179.21 ±1.34 187.89 ±1.09 F4 181.39 ±0.98 189.01 ±0.98 F5 179.76 ±1.32 186.96 ±1.42 F6 183.12 ±2.24 190.32 ±1.08 F7 180.09 ±1.08 187.34 ±1.12 F8 178.12 ±1.24 184.52 ±1.33 F9 179.35 ±1.02 187.01 ±1.14 F10 180.45 ±0.98 188.00 ±1.11 F11 181.32 ±1.23 188.67 ±1.28 F12 182.45 ±1.11 189.79 ±1.20 Hardness Hardness indicates the ability of a tablet to withstand mechanical shocks while handling. Hardness of both core and coated tablets were determined using a Monsanto hardness tester. It is expressed in kg/cm2. Three tablets were randomly picked from each batch and analyzed for hardness. The mean and standard deviation were also calculated. Table no. : Data for hardness of all formulations Formulation Code Hardness (kg/cm2)(n=3) (mean ±SD) Before Coating After Coating F1 5.06 ±0.19 6.18 ±0.22 F2 5.21 ±0.26 6.29 ±0.42 F3 4.96 ±0.32 6.03 ±0.15 F4 5.02 ±0.22 6.41 ±0.32 F5 5.28 ±0.18 6.17 ±0.18 F6 5.11 ±0.33 6.25 ±0.28 F7 4.89 ±0.25 6.00 ±0.33 F8 4.99 ±0.14 6.32 ±0.36 F9 5.08 ±0.18 6.75 ±0.25 F10 4.99 ±0.25 5.98 ±0.12 F11 5.12 ±0.33 5.90 ±0.21 F12 4.97 ±0.10 5.96 ±0.19 Friability (F) It is the phenomenon whereby tablet surfaces are damaged and/or show evidence of lamination or breakage when subjected to mechanical shock or attrition. The  friability of core tablets was determined using Roche Friabilator. It is expressed in percentage (%). Twenty core tablets were initially weighed (Winitial) and transferred into friabilator. The friabilator was operated at 25 rpm for 4 minutes or run up to 100 revolutions. The tablets were weighed again (Wfinal). The % friability was then calculated % Friability = ((A-B)/A) Ãâ€" 100 Where, Formulation Code Friability (%) (n=10) F1 0.010 F2 0.015 F3 0.017 F4 0.012 F5 0.009 F6 0.016 F7 0.014 F8 0.013 F9 0.012 F10 0.015 F11 0.014 F12 0.012 A = Initial weight of tablets B = Final weight of tablets after 100 revolutions Friability of tablets less than 1% are considered acceptable. Drug content The famotidine core tablets were tested for their drug content. Five tablets were finely powdered; quantities of the powder equivalent to 100 mg of famotidine were accurately weighed and transferred to a 100 ml of volumetric flask. Made up to 100ml with 4.5 phosphate buffer. From the above solution 1ml was taken and made up to100 ml with phosphate buffer (pH 4.5) From the above solution 10 ml was taken and made up to100 ml with phosphate buffer (pH 4.5) i.e.,10 µg/ml solution and measure the absorbance of the resulting solution at 265 nm using a Shimadzu UV-visible spectrophotometer. The linearity equation obtained from calibration curve was used for estimation of famotidine in the tablet formulations. Formulation Code Assay (%) F1 99.25 ±0.042 F2 98.32 ±0.052 F3 99.15 ±0.016 F4 99.52 ±0.019 F5 101.95 ±0.021 F6 99.25 ±0.034 F7 99.98 ±0.028 F8 98.74 ±0.052 F9 98.23 ±0.061 F10 100.12 ±0.011 F11 99.52 ±0.021 F12 99.56 ±0.023 Table no. : Data for drug content of all formulations In-Vitro Dissolution Studies The developed formulations of were subjected in vitro dissolution studies using USP Type II dissolution apparatus (Electrolab, India) with a speed of 50 rpm. The dissolution study was carried out in 900 ml dissolution media maintained at 37 ±0.5 oC. At suitable time interval, 10 ml samples were withdrawn and replaced with equivalent amount of fresh medium to maintain sink conditions. Samples withdrawn were filtered and analyzed at 265 nm using a UV spectrophotometer. After analyzing the drug content in the dissolution samples, cumulative percentage of drug release versus time was plotted. The general conditions for in vitro dissolution studies are as summarized below. Dissolution conditions: Medium : 4.5 phosphate buffer Volume: 900 ml Temperature: 37  °C  ± 0.5  °C Apparatus: USP Type-II (paddle) Rpm: 50 Time intervals : 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 12 hr Samples were suitably diluted and absorbance was measured. Cumulative percentage drug released was calculated for each batch. The study was performed in triplicate and the average was reported. Table no. : In-Vitro data drug release data for formulation F-1 S.no Time Cumulative % drug release 1 0 0 2 1 2.81 ±2.75 3 2 4.00 ±1.64 4 3 6.67 ±2.56 5 4 10.61 ±1.98 6 5 13.07 ±2.84 7 6 16.31 ±1.27 8 7 18.56 ±1.32 9 8 21.86 ±0.99 10 10 27.07 ±1.46 11 12 32.76 ±1.21 Figure no. : In-Vitro drug release of formulation F-1 Table no. : In-Vitro data drug release data for formulation F-2 S.no Time Cumulative % drug release 1 0 0 2 1 2.10 ±2.84 3 2 4.21 ±1.95 4 3 7.52 ±2.95 5 4 10.61 ±2.09 6 5 13.07 ±1.95 7 6 16.31 ±2.75 8 7 18.56 ±2.94 9 8 21.86 ±1.24 10 10 32.16 ±1.89 11 12 40.79 ±1.11 Figure no. : In-Vitro drug release of formulation F-2 Table no. : In-Vitro data drug release data for formulation F-3 S.no Time Cumulative % drug release 1 0 0 2 1 4.02 ±3.72 3 2 8.04 ±1.34 4 3 13.34 ±2.83 5 4 18.63 ±1.52 6 5 22.90 ±1.32 7 6