Formulation And Evaluation Of Paracetamol Tablets .
Research In Pharmaceutical Biotechnology Vol. 2(3), pp.25-32, June 2010Available online at http://www.academicjournals.org/RPBISSN 2141-2324 2010 Academic JournalsFull Length Research PaperFormulation and evaluation of paracetamol tabletsmanufactured using the dried fruit of Phoenixdactylifera Linn as an excipientN. C. Ngwuluka*, B. A. Idiakhoa, E. I. Nep, I. Ogaji and I. S. OkaforDepartment of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, University of Jos,P. M. B. 2084, Jos, Nigeria.Accepted 19 May, 2010Dried and milled date palm fruit was evaluated for its binding properties in comparison with acacia andtragacanth. Characterization of the granules in addition to quality control tests that included uniformityof weight, hardness, friability, disintegration and dissolution were undertaken. The granulesmanufactured using the binders had good flow properties and compressibility. As the concentration ofthe binders increased, the binding ability improved producing tablets with good uniformity of weightand hardness. The tablets manufactured using dried date palm was found to be less friable than tabletsmanufactured using acacia and tragacanth. Although, the tablets did not disintegrate, the drug releasefrom the tablets passed the USP and BP specification for dissolution of paracetamol. Therefore, drieddate palm fruit may be explored as a pharmaceutical excipient.Key words: Date palm, quality control tests, disintegration, dissolution, weight variation, paracetamol.INTRODUCTIONNatural polysaccharides are widely used in thepharmaceutical and food industry as excipients andadditives due to their low toxicity, biodegradable,availability and low cost. Excipients are essentialingredients of a dosage form which are added to increasevolume, aid flow, enable compactness and make a drugconvenient to administer. They can also be used tomodify the release of drug, thereby, influencing theabsorption and subsequent bioavailability of theincorporated drug. Furthermore, they act as vehicleswhich transport the incorporated drug to the site ofabsorption and are expected to guarantee the stability ofthe incorporated drug, the precision and accuracy of thedosage, and also improve on the organoleptic propertiesof the drugs where necessary in order to enhance patientadherence (Pifferi et al., 1999). They should optimize theperformances of dosage forms during manufacturing aswell as when patients ingest them (Pifferi and Restani,*Corresponding author. E-mail: ngwuluka@unijos.edu.ng.2003).Date fruit is an edible fruit composed of amino acidsand proteins, carbohydrates, fatty acids, salts andminerals, and dietary fibre (Al-shahib and Marshall,2003). Carbohydrates make up to 44 - 88% of the fruitwhich include mainly reducing sugars such as fructose,sucrose, mannose, glucose and maltose in addition tosmall amounts of polysaccharides such as pectin (0.5 3.9%), starch and cellulose (Al-shahib and Marshall,2003). The protein content is approximately 2.3 - 5.6%with 23 amino acids which include alanine, aspartic acid,serine, glutamic acid, threonine, proline and glycine.There are 15 types of fatty acids such as arachidic,palmitic, stearic, myristic, capric, lauric and behenicacids, which make up about 0.2 - 0.5% of the fruit.However, eight of the fatty acids are found in the fleshypart of the fruit. The mineral content includes iron, cobalt,calcium, potassium, fluorine, copper, magnesium,phosphorus, sodium and zinc. Some varieties of datepalm can produce as much as 400 - 600kg fresh fruitsper annum for a span of 60 years and these fruits areavailable 8 months of the year (Al-shahib and Marshall,2003). The moisture content decreases as they ripen
26Res. Pharm. Biotech.Table 1. Compositions of paracetamol tablets at different concentrations of the binder.IngredientsParacetamolLactoseBinderCorn starchTalcMagnesium stearateBatch I (%)2% binder71.419.62.05.01.01.0Batch II (%)5% binder71.416.65.05.01.01.0from 83.6% to as low as 12.7% in dried state. Date palmfruit has been studied for its antioxidative andantimutagenic activities (Vayalil, 2002). However, little isknown of its use as a pharmaceutical excipient.This study was undertaken to explore the ability ofdried date palm fruit to act as a binder in tabletmanufacturing. To evaluate the binding properties of datepalm, characterization of granules and tablets and in vitrodrug release studies were undertaken.MATERIALS AND METHODSMaterialsParacetamol BP (Zhengzhou United Asia Trading Co.,Ltd,Zhengzhou, Henan, China), corn starch (G Koepcek E and CoGMBH, Sachsenfeld, Hamburg, Germany), lactose (Milkaut,Rivadavia, Franck - Pcia. de Santa Fe), talc (Hopkins and Williams,Chadwell Health Essex, England), Magnesium stearate (GurrChemicals, Bell Sons and Co, Southport, England), acacia (BDHChemical Ltd, Poole, England) and tragacanth (Steculia GumHalewood Chemicals Ltd, Stanwell Moor, Staines, Middlesex,England). Hydrochloric acid was of analytical grade.Batch III (%)10% binder71.411.610.05.01.01.0Batch IV (%)20% binder71.41.620.05.01.01.0Evaluation of granulesParticle size distribution of the granulesParticle size distribution of the granules was determined by meshanalysis employing a stack of sieves after granules had beenweighed (34 g) and the granules were shaken for 10 min. Thequantities of granules on each sieve were obtained gravimetrically.Evaluation of bulk and tapped densities of the granulesThe volume of a known quantity of the granules from each batchwas obtained before and after tapping. The volume before tappingwas used to determine the bulk density while the volume aftertapping was employed to determine the tap density mathematically.Furthermore, Hausner’s quotient and Carr’s compressibility indexused to determine the flow and compressibility properties ofgranules were obtained from the equations:Hausner’s quotient Carr’s compressibility Tapped density1BulkTapped density – Bulk densityTapped densityX 1002Preparation of dried powdered date palmAssessment of rate of flow and angle of reposeDate palm fruits were bought from a local market in Jos, Nigeria.The fruits are usually sold partially dried. The seeds were extractedfrom the fruit and discarded while the fleshy fruits were further driedover 24 h and milled to powder for use as a binder.A simple method whereby weighed quantity of granules from eachbatch was allowed to flow through an orifice (funnel) at a fixedheight was used to determine flow rate. The time taken for theweighed granules to flow out completely from the orifice wasrecorded. This was performed in triplicate. Flow rate was obtainedby the equation below:Manufacture of tablets employing wet granulation methodFlow rate Wet granulation method of tablet manufacturing was employed withmilled date palm as a binding agent and water as the granulatingliquid. Batches of paracetamol tablets were formulated using 2, 5,10 and 20%w/w of date palm powder. Paracetamol, lactose, datepalm mucilage and corn starch were blended to form a dampcoherent mass which was screened through a sieve No 10 anddried at 60 C for one hour. Corn starch was divided into two andincorporated during wet blending and after drying of granules to actas an intragranular and extragranular disintegrant. For comparativepurposes, acacia and tragacanth gums were also used as bindersat the same concentrations as date palm. The compositions of thebatches are shown in Table 1.Weight of granulesTime (sec)3Furthermore, the angle of repose was determined by calculating tanfrom the height and radius of the cone formed by the granules asthey flowed out of the orifice and subsequently obtaining theinverse of tan .Compression of granulesThe granules were blended with the disintegrant (corn starch),glidant (talc) and lubricant (magnesium stearate). The blend was
Ngwuluka et alcompressed using a single punch tableting machine (Manesty TypeF3, Liver Poole, England) with a punch diameter of 0.75 cm set at933 Pa (N/m2) compression pressure. The die volume was tocorrespond to the weight of the tablet to ensure that 500 mgparacetamol is obtained.Evaluation of the batches of tabletsCompendial and non-compendial tests were undertaken to assessthe quality and performance of the batches with different binders incomparison with one another. These tests include uniformity ofweight and diameter, hardness, friability, disintegration time anddissolution.Uniformity of weight and diameter of tabletsTwenty tablets were randomly selected from each batch andassessed gravimetrically on an individual tablet basis. The meanweight as well as standard deviation were calculated. Thediameters of the tablets were determined by employing amicrometer screw gauge (Sterling Manufacturing Company, India).Mechanical strength of tabletsAlthough, the crushing strength test is non-compendial, it isundertaken to determine the ability of the tablets to withstandpressure during handling, packaging and transportation. Amonsanto tablet hardness tester (Copley Scientific Ltd, Nottingham,United Kingdom) was employed to determine the mechanicalstrength of the tablets. The average force required to crush thetablets from each batch was obtained.Friability testing of tabletsTo evaluate the degree of friability of the tablets from each batch,ten tablets were randomly selected, dusted and weighed. Thetablets were placed in a Roche friabilator (Erweka Gmbh, Germany)and subjected to its tumbling actions at 25 revolutions per minutefor four minutes. Afterwards, the tablets were once again dustedand reweighed to determine the percentage loss of weight.Disintegration studies on the tabletsSix tablets from each batch were utilized for disintegration studiesin distilled water at 37 C using an Educational SciencesDisintegration Apparatus (Es Eagle Scientific Limited, Nottingham,United Kingdom). The disintegration time was taken to be the timeno granule of any tablet was left on the mesh of the apparatus.In vitro drug release studiesIn vitro drug release studies were undertaken using USP apparatusI (basket method). The dissolution medium was 1000 mL of 0.1 NHCl at 37 C for 30 min to depict the gastric medium where thetablets will disintegrate. In all experiments, 5 mL of sample waswithdrawn at 5 min interval and replaced with fresh medium tomaintain sink condition. Samples were filtered and assayedspectrophotometrically at 230 nm.Data analysisSimple statistical analysis was utilized for content uniformity ofweight, uniformity of diameter and uniformity of thickness while27dissolution efficiency (DE) was used for the in vitro dissolutionstudies.RESULTS AND DISCUSSIONThe powder obtained from milling dried fruit of phoenixDactylifera was brown in colour. On hydration, rapidswelling was observed which generated viscous mucilagethat was utilized as a binder for wet granulation method.Granulation is employed in pharmaceutical manufacturingdue to the poor flow and compaction of powders (Kryceret al., 1983). Wet granulation is a pharmaceutical processof tabletting which provides better uniformity of contentespecially for low drug concentrations, controls productbulk density as well as compaction of even high drugcontents (Faure et el., 2001). Furthermore, it improvesflow and handling, appearance, mixture’s resistance tosegregation and reduces variation in tablet dissolution(Kristensen and Schaefer, 1987; Westerhuis andCoenegracht, 1997; McConville et al., 2004). The type ofbinder used in granulating influences the properties of thegranules as well as the quality of the tablets produced(Becker et al., 1997). Wet granulation is basically theaddition of a binder solution or a solvent to a powdermixture; sieving to generate granules and subsequentgranule drying.Evaluation of granulesParticle size distribution of granules is evaluated due to theimpact of granule size on flowability, uniformity of weight andcontent, compression, dissolution and subsequently, drugrelease (Yalkowsky and Bolton, 1990; Fichtner et el.,2005; Rohrs et al., 2006; Virtanen et al., 2010). Particlesize and particle size distribution affects the compatibilityand rearrangement of particles (Virtanen et al., 2010).Though, there are exceptions, the flow properties ofgranules are improved when the particles are large and theparticle size distribution is narrow. However, largerparticles lead to less strong tablets due to the fact thatthey have lesser surface areas for bond formation ascompared to smaller particles (Sun and Himmelspach,2006). Hence, an optimal particle size and size distributionwill be required to obtain good flow properties, compactionand hardness.The particle sizes of the paracetamol granules increasedas the concentration of the binders increased as shown inFigure 1. This applied for both date palm and tragacanth;however for acacia, particle size increased asconcentration increased to 10% and then a decrease inparticle size was observed at 20% concentration ofacacia. It may be an indication that the bindingmechanism of acacia changes above 10% (Becker et al.,1997). There were much less fine particles which impliedthat the granules may have good flow properties.However, less fine particles may indicate that there wouldbe more unfilled voids during the process of compression
28Res. Pharm. Biotech.abcwhich may lead to less hard and friable tablets. Granulesprepared with date palm as a binder compared moremeasurably with those prepared with acacia and morespecifically with tragacanth.Other parameters for assessing the properties ofgranules which include flow rate, angle of repose, bulkand tapped densities, Hausner quotient and Carr’scompressibility are shown in Table 2. Compressibility ofgranules is determined so as to assess the ability of thegranules to compact and decrease in volume whenpressure is applied. This is needed to ensure that thesuitability of the granules for tabletting in order to producestrong tablets which can withstand pressure.Compressibility index is also an indicative of the flowproperties of granules while Hausner quotient relates tothe cohesiveness of the granules (Mohammadi andHarnby, 1997). When the percentage compressibility isbelow 15% the granules have excellent flow propertieswhile cohesive granules have percentage compressibilityabove 25% indicating poor flow properties (Endale et al.,2008; Bacher et al., 2008). Granules with Hausner ratiobelow 1.25 have good flow properties (Panda et al.,2008) and granules with angle of repose below 40º Cbutpreferably below 30º Cexhibit good flow (Reddy et al.,2003) while granules with 50º would flow with difficulty(Reus-Medina et al., 2004).Therefore, granules prepared by using different binders- date palm, acacia and tragacanth - exhibited good flowproperties and satisfactory compressibility. Carr’scompressibility and Hausner ratio were below 15% and1.25, respectively, for the different concentrations of the binders while angle of repose was below 40 C for thedifferent binder concentrations except 2% tragacanth.The flow properties of granules are determined due to itseffect on the uniformity of weight of tablets. Hence, it isenvisaged date palm as a binder would exhibit lessvariation in the uniformity of weight of tablets.Evaluation of tabletsdFigure 1. (a) Particle size distribution of granules employing date palmas a binder at different concentrations. NB: A, B, C depicts the weightsof the granules on each sieve: A is for sieve with mesh number 60; B –mesh number 80 and C is 100. (b) Particle size distribution of granulesemploying acacia as a binder at different concentrations. (c) Particlesize distribution of granules employing tragacanth as a binder atdifferent concentrations. (d) comparative particel size distribution of thedate palm, acacia and tragacanth at mesh number 60.A summary of the properties of the tablets formulated forthe batches employing the different binders are shown inTable 3 (Ferrari et al., 1996). Uniformity of weight,thickness and diameter are indication of the amount ofactive pharmaceutical ingredient (API) in the tablets,however, it is not a guarantee that the API is uniform inall tablets especially in formulations with low doseconcentrations.Furthermore, should weights, thickness or diameter oftablets in a batch vary, there will be variations indisintegration and dissolution. The compendial specification for uniformity of weight states that for tabletsweighing more than 324 mg, weights of not more thantwo tablets should deviate from the average weight bymore than 5% (USP, 1995). The tablets from the differentbatches which had different binders and at different
Ngwuluka et al.29Table 2. Characterization of the granules prepared by the different binders.oAngle of repose ( )Flow rate (g/sec)Bulk density (g/mL)Tapped density (g/mL)Hausner quotientCarr’s compressibility (%)Date palm powder2%5%10%20%29.74 28.02 26.66 0.940.9011.11Acacia gum5%10%31.56 Tragacanth gum5%10%28.90 .995.520.440.471.076.85Table 3. Compendial and non-compendial tests for tablets prepared by the different binders.Uniformity of weight (g)Std. dev.Uniformity of diameter (mm)Std. dev.Uniformity of thickness (mm)Std. dev.Hardness (kg)Friability (%)Disintegration (min)Date palm powder2%5%10%20%0.703 0.693 0.694 0.7000.008 0.014 0.015 0.0070.954 0.956 0.965 0.9850.002 0.002 0.002 0.0030.280.280.290.290.003 0.002 0.002 0.0026.008.508.50 1424.89 11.34 7.220.93 30 30 30 30concentrations met the compendial specification.Crushing strength test shows the ability of tablets towithstand pressure or stress during handling, packagingand transportation. It is the property of a tablet that ismeasured to assess its resistance to permanentdeformation. Furthermore, the mechanical strength of atablet determines the disintegration time and the rate ofdissolution. As the concentration of the binder increases,the mechanical strength increases. This was obtainablefor date palm and tragacanth while there was no furtherincrease in mechanical strength when 20% acacia wasused. For the mechanical strength of a tablet to besatisfactory, the minimum requirement is 4 kg (Allen etal., 2004). As shown in Table 3, 2% acacia andtragacanth did not comply with the specification. All theconcentrations of date palm met the specificationsimplying that date palm produced tablets with goodmechanical strength.Friability is another mechanical property of a tablet withcompendial (USP, 1995) specification not more than 1%.While crushing strength test is a bulk deformation of thetablet, friability is a surface deformation which may beenhanced by the morphology of the tablet (Riippi et al.,1998). The rougher the surface of the tablet, the morefriable it will be. It was observed that paracetamol tabletsprepared with acacia and tragacanth were friable thoughhard as the concentration of the binder increases. 2%2%0.6990.0070.9640.0050.290.004 3.5023.1823Acacia gum5%10%0.697 0.6930.004 0.0100.966 0.9670.004 0.0030.230.210.004 0.0034.008.5012.44 18.5227 3020%0.6990.0060.9650.0020.260.0038.5026.65 302%0.6900.0100.9670.0070.270.0051.005Tragacanth gum5%10%0.692 0.6730.019 0.0240.966 0.9650.006 0.0070.200.210.006 0.0074.506.259.89 11.1571120%0.6970.0240.9660.0060.220.006 1424.8914tragacanth could not withstand the friability test due to itssoftness. On the contrary, the friability of the tabletsprepared with date palm decreases as the concentrationof the binder increases. However, only 20% date palmmet the compendial specification for friability.Disintegration is a crucial step in release of drugs fromimmediate release dosage forms. The rate ofdisintegration is directly proportional to the rate ofdissolution. The rate of disintegration is influenced by therate of influx of water into the tablets which is alsodepe
Formulation and evaluation of paracetamol tablets manufactured using the dried fruit of Phoenix dactylifera Linn as an excipient N. C. Ngwuluka*, B. A. Idiakhoa, E. I. Nep, I. Ogaji and I. S. Okafor Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, University of Jos, P. M. B. 2084, Jos, Nigeria. Accepted 19 May, 2010 Dried and milled date palm fruit .
The central analgesic action of paracetamol is like aspirin, i.e. it raises pain threshold, but has weak peripheral anti-inflammatory component. Analgesic action of aspirin and Paracetamol is additive. Paracetamol is a good and promptly acting antipyretic. Paracetamol has negligible anti-inflammatory action. It is a poor inhibitor of
group [3], meaning it has good solubility and low permeability [4]. Excipients of IR tablet formulation include fi llers, binders, glidants and desinte-grants. Paracetamol tableting mass is prepared usually by wet granulation since it contain high dose of paracetamol that has poor com-pressibility and low fl owability [5, 6, 7]. Th e
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Acid-base titration of paracetamol in nonaqueous solvents was done. Procedure was followed for titration of paracetamol in different media like acetic acid, pyridine, dimethlformamide and ethyl alcohol with standard perchloric acid in glacial acetic acid, sodium ethoxide in ethyl alcohol u
Wight of p-Aminophenol on acetylation with Volume of acetic anhydride yields Paracetamol Wight g Hence, Theoretical yield of Paracetamol g Reported Practical yield g Therefore, Percentage
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Formulation and evaluation of almotriptan chewable tablets 1V. Anil kumar*, K.L. Deepthi*, 1R. Kalyani, 1B. Padmasri, 2D.Prasanth . in the formulation of a chewable tablet is to obtain a complete profile of the active drug. This usually leads to the most efficient formulation of a stable and quality product as the drug usually dictates the choice of fillers, carriers, sweeteners, flavor .
toute la chaîne alimentaire, depuis la production primaire jusqu’à l’assiette du consommateur. La Commission du Codex Alimentarius – un lieu de débat où traiter des questions nouvelles et difficiles Après 45 ans d'activité, la Commission du Codex Alimentarius conserve toute son actualité et il serait difficile d'envisager un monde sans elle. La Commission est toujours prête à .
