Testing Drug Content of Famotidine Core Tablets

Testing Drug Content of Famotidine Core tabularizets6. Formulation development and evaluation6.1 Preparation of core a nary(prenominal)latory drugsCore birth control pills of famotidine were prepared by direct compression and batch size was unploughed as 100 tablets.Drug , sodium chloride, polymer and MCC were co-sifted through sieve 30Now the blend is fuse in polybag for 10 minCitric acid was crushed apply mortar and pestle and sifted through sieve 60And this is added to above blend and commingle 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 minNow the blend is compressed to tablets having the total cant over of 180 mg using 8 mm round concave punch and at low relative humidity 20 % RH6.2 finale of core tablets 6.2.1. Preparation of coating solution5 ml of water was taken in a beaker and to this required amount of PEG 400 was added and dissolved95 ml of acetone was taken in a beaker and stirred at cl rpm using electrical stirrer to this above solution was added and stirred for 5 minNow to the above solution 5 gm of cellulose ethanoate 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 membraneCoating 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 belowInlet temperature 40 oC 2 oCBed temperature 35 oCrpm of pan 15 -17Spray rate 3-7 ml/minAtomizing air drag 2.0 psiCoating was done until required weight take up was achievedDrilling of orifice The orifice was made using needles of different sizes i.e, 24, 22 guageINGREDIENTSF1F2F3F4F5F6Core tablet mg/tabletFamotidine404040404040Citric acid202020202020Sodium chloride505050505050HPMC k100M918Polyox11057.2Polyox 3017.2Polyox3037.2Sodium lauryl sulphate3.63.63.63.63.63.6Magnesium stearate1.81.81.81.81.81. 8 powder3.63.63.63.63.63.6Avicel PH 102434353.853.853.853.8Total wt of tablet180180180180180180Coating solutionCellulose acetate5 gm15 % w/w of total solids (0.669 ml)4 mlUpto 100 ml4%PEG 400 piddleAcetone weightiness deductCoated tablets were left over night for dryingTable 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 gainINGREDIENTSF7F8F9Core tablet mg/tabletFamotidine404040Citric acid202020Sodium chloride505050Polyox 30110.810.810.8Avicel PH 10250.850.850.8Sodium lauryl sulphate3.63.63.6Magnesium stearate1.81.81.8Talc3.63.63.6Total wt of tablet180180180Coating solutionCellulose acetate5 gmPEG 40015 % w/w of total solids (0.669 ml)Water4 mlAcetoneUpto 100 ml cant over gain4 %3 %5 % Table 6.10 Formulation trails of optimum plasticizer concentrationINGREDIENTSF 10F 11F 12Core tablet mg/tabletFamotidine404040Citric acid202020Sodium chloride505050Polyox 30110.810.810.8 Avicel pH 10250.850.850.8Sodium lauryl sulphate3.63.63.6Magnesium stearate1.81.81.8Talc3.63.63.6Total wt of tablet180180180Coating solutionCellulose acetate5 gm5 gm5 gmPEG 400(% w/w of total solids)20%(0.89 ml)25%(1.25 ml)35%(1.4 ml)Water4 ml4 ml4 mlAcetoneUpto 100 mlUpto 100 mlUpto 100 mlWeight gain4%4%4%6.3 Evaluation of blend 6.3.1 bung of reposeAngle of reposeWeighed 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 visual sense, and the height of pile were measured and the angle of repose was calculated using the formula(h/r)h = height of the piler = radius of the base of the conical pile Table 6.4 Flow station and corresponding angle of reposeFlow propertyAngle of repose ()Excellent25 30Good31 35Fair-no need of aid36 40Passable hang up chances41 45Poor must vibrate, agitate46 55 actu anyy poor56 65Very, very poor66Formula tion codeAngle of reposeF125.45F222.92F323.13F419.20F518.62F617.20F720.09Table no. Data for angle of repose of all formulations6.3.2 Bulk densityAn accurately weighed quantity of powder carefully poured into graduated cylinder. Then after pouring the powder into the graduated cylinder the powder posterior 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 multitude volume and the mint density is calculated by following formulaBulk density = Weight of powder / Bulk volumeTapped Density after(prenominal) 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 great 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 squeezability IndexIt 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 antecedently obtained bulk and tapped densities. Carrs index = Tapped density Bulk density X 100 Tapped DensityHausner RatioIt 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 ratioFlow property C.I ( % )Hausner ratioExcellent101.00 1.11Good11 151.12 1.18Fair16 201.19 1.25Passable21 251.26 1.34Poor26 311.35 1.45Very poor32 371.46 1.59Very, very poor381.60Formulation codeBulk density(gm/cm3)Tapped density (gm/cm3)Carrs index (%)Haussners ratioAngle of reposeF10.4860.63122.91.2525.45F20.4100.51320.081.2522.92F30.4380.60118.2591.18 23.13F40.4360.58316.391.19619.20F50.4300.52017.311.2118.62F60.4620.53513.641.1617.20F70.4460.52314.721.1720.09Table no. Data for Bulk density, Tapped density, Compressibility index and Hausners ratio of all formulations6.4 Post compression studies6.4.1 Weight variationThe average weight of core tablets and coated tablets were determinedusing a digital weighing balance. 20 tablets were selected randomly from individually 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 variationIP/BPLimitUSP80 mg or less10%130mg or lessMore than 80mg or Less than 250mg7.5%130mg to 324mg250mg or more5%More than 324mgTable no. Data for weight variation test of all formulationsFormulation statute Avg weight(mean%deviation)BeforeCoating laterCoatingF1178.42 1.02185.721.12F2181.31 0.91188.791.45F3179.211.34187.891.09F4181.390.98189.010.98F5179.761. 32186.961.42F6183.122.24190.321.08F7180.091.08187.341.12F8178.121.24184.521.33F9179.351.02187.011.14F10180.450.98188.001.11F11181.321.23188.671.28F12182.451.11189.791.20HardnessHardness indicates the ability of a tablet to withstand automatonlike shocks while handling. Hardness of both core and coated tablets were determined using a Monsanto hardness tester. It is expressed in kg/cm2. leash 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 formulationsFormulationCodeHardness(kg/cm2)(n=3)(meanSD)BeforeCoatingAfterCoatingF15.060.196.180.22F25.210.266.290.42F34.960.326.030.15F45.020.226.410.32F55.280.186.170.18F65.110.336.250.28F74.890.256.000.33F84.990.146.320.36F95.080.186.750.25F104.990.255.980.12F115.120.335.900.21F124.970.105.960.19friability (F)It is the phenomenon whereby tablet surfaces are damaged and/or show evidence of lamination or breakage when subjected to mech anical shock or attrition. Thefriability 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) 100Where,FormulationCodeFriability(%)(n=10)F10.010F20.015F30.017F40.012F50.009F60.016F70.014F80.013F90.012F100.015F110.014F120.012A = Initial weight of tabletsB = Final weight of tablets after 100 revolutionsFriability of tablets less than 1% are considered acceptable.Drug contentThe 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 tak en 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.,10g/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.FormulationCodeAssay(%)F199.250.042F298.320.052F399.150.016F499.520.019F5101.950.021F699.250.034F799.980.028F898.740.052F998.230.061F10100.120.011F1199.520.021F1299.560.023Table no. Data for drug content of all formulationsIn-Vitro decay StudiesThe developed formulations of were subjected in vitro dissolution studies using USP Type II dissolution apparatus (Electrolab, India) with a speed up of 50 rpm. The dissolution study was carried out in 900 ml dissolution media maintained at 370.5 oC. At suitable time interval, 10 ml samples were withdrawn and replaced with equivalent amount of fres h 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 reverse versus time was plotted. The general conditions for in vitro dissolution studies are as summarized below. Dissolution conditionsMedium 4.5 phosphate bufferVolume 900 mlTemperature 37 C 0.5 CApparatus USP Type-II (paddle)Rpm 50 period intervals 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 12 hrSamples 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-1S.noTimeCumulative % drug release100212.812.75324.001.64436.672.565410.611.986513.072.847616.311.278718.561.329821.860.99101027.071.46111232.761.21Figure no. In-Vitro drug release of formulation F-1Table no. In-Vitro data drug re lease data for formulation F-2S.noTimeCumulative % drug release100212.102.84324.211.95437.522.955410.612.096513.071.957616.312.758718.562.949821.861.24101032.161.89111240.791.11Figure no. In-Vitro drug release of formulation F-2Table no. In-Vitro data drug release data for formulation F-3S.noTimeCumulative % drug release100214.023.72328.041.344313.342.835418.631.526522.901.3276