A Systematic Study on Flowability and Compressibility of Asparagus racemosus root Powder for Tablet Preparation

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1 Nianjan Pata Ch et al. : A Systematic Study on Flowability Reseach Pape 129 A Systematic Study on Flowability and Compessibility of Aspaagus acemosus oot Powde fo ablet Pepaation Nianjan Pata Ch *, Satya Pakash Singn, Hemant Kuma P, Vimala Devi M. PG Depatment of Phamaceutics, College of Phamaceutical Sciences, Behampu, Oissa, India ABSRAC: he died oot of Aspaagus acemosus is widely used as mild antihypetensive and tanquilize. he objective of the pesent eseach was to study the oiginal flowability, compessibility and compactibility of Aspaagus acemosus oot powde and develop its tablet fomulations by wet ganulation and diect compession technology. he consolidation behavio of dug and tablet fomulations wee studied by using Heckel and Leuenbege equation. Aspaagus acemosus oot powde showed vey poo flowability and compactibility. Kawakita analysis evealed impoved flowability fo fomulations pepaed by diect compession and wet ganulation technique. he Heckel plot showed that Aspaagus acemosus powde is soft in natue and poo in die filling. Ganules showed highe degee of plasticity and fagmentation than powde and diect compession fomulations. he compession susceptibility paamete fo compact fomed by diect compession and wet ganulation technique indicated that the maximum cushing stength is eached faste at lowe pessues of compession as opposed to Aspaagus acemosus powde. Fom this study, it is concluded that desied flowability, compessibility and compactibility of Aspaagus acemosus oot powde can be obtained by diect compession and wet ganulation technique. KEY WORDS: Aspaagus acemosus, flowability, compessibility, tablets. Intoduction he died oot of Aspaagus acemosus, Family Liliaceae, contains steoidal saponins and sapogenins (Oketch-Rabah, 1998). It is commonly mentioned as a asayana in the ayuveda. Aspaagus acemosus has been used fo the teatment of dyspepsia and as a gelactogogue (Dalvi et al., 1990). Aspaagus acemosus was found to offe potection against vaiety of biological, physical and chemical stessos (Rege et al., 1999, and Bhattachaya et al., 2000). It has also been efeed as nevine tonic, sexual tonic, diuetic, ejuvenating, caminative, stomachic and antiseptic (Chopa et al., 1994). It is maketed as a single dug fomulation in powde dosage fom and also as a tablet and capsule along with some othe hebal dugs. A need fo systematic study on fomulation development of a tablet dosage fom of Aspaagus acemosus oot powde exists. his study is an attempt on those lines. he measuement of poosity change as a function of compession pessue is widely used in descibing the powde compessional behavio. he compessibility of a powde bed could be infeed fom the elationship between poosity and applied pessue (Paonen et al., 1996). Due to poo flowability and compaction behavio, Aspaagus acemosus oot powde fequently equies alteation pio to tabletting. Diect compession of powdes equie mateials exhibiting good flowability, * Coesponding autho: Ch. Nianjan Pata Ph: (O); Fax: pato_nianjan@ediffmail.com compactibility and compessibility. hese paametes become moe citical when the fomulation contains lage amount of active substances with poo compessional popeties. Wet ganulation method is selected fo poduction of poous and fee-flowing ganules, which enables to fom tablets with high mechanical stength at low compession pessue. In the pesent study, the influence of alteation in paticle size and diect compession on the development of tablet fomulations of Aspaagus acemosus oot powde wee investigated. Flowability, compactibility and compessibility (Shileout et al., 2000) wee systematically investigated with an aim to undestand the consolidation behavio. Mateials and Methods he oot of Aspaagus acemosus was collected fom vicinity egions of Mohuda, Ganjam distict of Oissa, India and was identified and authenticated by Botanist of PG Dept of Biosciences, Affiliated to Behampu Univesity, India. he vouche specimen (0126/07/PGDB/BU) has been deposited in thei epositioy hebaium fo futue veification and efeence. he oot was died unde shade and finally powdeed and sieved though sieve no. 85/100. Avicel PH101, Avicel PH 102 and Silicified MCC wee the gatis samples eceived fom Ranbaxy Lab ltd. India. All othe chemicals used wee of analytical gade. 129

2 130 Intenational Jounal of Phamaceutical Sciences and Nanotechnology Volume 1 Issue 2 July - Septembe 2008 Pepaation of Ganules he wet ganulation method of massing and sceening was used with a batch size of 500 tablets. Aspaagus acemosus oot powde (80 % w/w) and Avicel PH 101 (15 % w/w) wee dy mixed fo 10 minutes in a wet ganulato WGS (kalweka Seies, Kanavati Engineeing Ltd, India). he dy mix was moistened with an appopiate amount of 10 % stach paste (w/v) and subjected to wet mixing fo 15 minutes in the same wet ganulato. he wet mass was passed though sieve No. 16. he ganules wee died in a hot ai oven (Hicon India Ltd, India) fo 4 hs at 60 o C and then e-sieved though sieve No.16. alc (1 %) and magnesium steaate (1 %) was added and mixed fo 5 min in a cube mixe (Kalweka seies, Kanavati Engineeing Ltd, India). Pepaation of Diect Compession Fomulation In diect compession method, Aspaagus acemosus oot powde (80 % w/w), Avicel PH102 (10 % w/w), silicified MCC (8 %), talc (1 %) and magnesium steaate (1 %) wee mixed fo 10 min in a cube mixe (Kalweka seies, Kanavati Engineeing Ltd, India). Fundamental Powde Popeties ue Density he tue densities of the Aspaagus acemosus oot powde, ganule and diect compession fomulations wee detemined by the liquid displacement method using immiscible solvent and the tue density was computed (n = 3) accoding to the equation: W1 = SG ( W + W ) W Whee W 1 is the weight of powde, SG is the specific gavity of the solvent, W 2 is the weight of bottle + solvent and W 3 is the weight of bottle + solvent + powde. Bulk and ap Density he bulk and tap density of each mateial was detemined by tapping method (n = 3) using digital tap density appaatus (Electo lab ltd. India). Flow Popeties Flow Rate he flow ate (Kasten et al., 2004) of the Aspaagus acemosus oot powde, ganule and diect compession fomulations wee detemined as the atio of mass (g) to time (seconds) using a steel funnel with an oifice diamete of 10 mm (n = 3). 3 Kawakita Analysis Flowability was detemined using the Kawakita analysis (Yamashio et al., 1983 and Kawakita et al., 1970). he method involved pouing a 10 g of powde and fomulations into a 50 ml glass measuing cylinde and the heap of the paticles in the cylinde was leveled off hoizontally with a thin metallic spatula, and the bulk volume Vo was accuately measued. hen tapping was stated mechanically and the change in volume of the powde column V N was noted afte N no of taps. he behavio of powde, ganule and diect compession fomulations in the tapping pocedue wee compaed using numeical constants obtained fom the Kawakita plots. he Kawakita equation, which is used fo assessing the flow popeties of powdes, is given by: N N 1 + C a ab =..2 Whee a and b ae constants; a descibes the degee of volume eduction at the limit of tapping and is called compactibility; 1/b is consideed to be a constant elated to cohesion and is called cohesiveness, C, the degee of volume eduction which is calculated fom the initial volume V 0 and tapped volume V N as: ( V0 VN ) C =..3 V 0 Numeical values fo constants a and 1/b ae obtained fom the slope, of plots of N/C vesus numbe of taps N (N = 10, 30, 100 and 300). Compaction Studies Pepaation of Compacts Compacts containing 500 mg of Aspaagus acemosus wee made fo oot powde, ganule and diect compession fomulation using a hydaulic pellet pess (Kimaya Enginees, India). Compession loads wee used in the ange of 10 Kg/cm 2 to 95 Kg/cm 2. hee compacts wee made at each compession level. Befoe compession, the die (13 mm diamete) and the flat- faced punches wee lubicated with a 2 % w/v dispesion of magnesium steaate in ethanol ethe (1:1). he compacts wee stoed ove silica gel fo 24 hous (to allow fo elastic ecovey, hadening and pevent falsely low yield values) befoe evaluations. he dimensions (thickness and diamete) and weight unifomity of thee compacts wee detemined. he elative density was calculated as the atio of appaent density of the compact to the tue density, of the A

3 Nianjan Pata Ch et al. : A Systematic Study on Flowability 131 powde. he data obtained using this ejected tablet method wee used to obtain the Heckel plots. Linea egession analysis was caied out ove a compession ange of 10 Kg/cm 2 to 95 Kg/cm 2 and paametes fom Heckel plots (Heckel., 1961 and Itiola., 1991) wee calculated. Heckel Equation he compaction chaacteistics of the powde wee studied with the Heckel equation. 1 ln = KP + A..4 1 A =..5 is the elative density of the compact, Whee, the appaent density and A is is the tue density, P is the applied pessue; K (the slope of the linea potion) is the ecipocal of the yield pessue, Py, of the mateial. he yield pessue is invesely elated to the ability of the mateial to defom plastically unde pessue and A is a function of the oiginal compact volume. Leuenbege Equation Fo compactability assessment, the foce equied fo diametal beaking of the compacts was detemined using a Digital hadness teste EH-01 (Electo lab ltd. India). ensile stength x of the compacts was calculated using the following equation (Esezobo et al., 1976). 2x x =..6 πdt Whee x is hadness (in Kg/cm 2 ) and d and t ae the diamete and thickness of the compacts (in mm), espectively. Leuenbege analysis was pefomed by fitting the data in the following equation (Leuenbege et al., 1986). A nonlinea plot of tensile stength with espect to poduct of compaction pessue P and elative density was obtained using statistical softwae (Gaph Pad Pism4): γ P = (1 e )..7 x Whee, is maximum tensile stength (kg/cm 2 ) when P will be infinite and will be equal to 1, and γ is compession susceptibility. Pepaation of ablet ablets containing 500 mg of Aspaagus acemosus wee poduced by compessing the ganules and diect compession fomulations using a single station tablet punching machine (Cadmach Machiney Co Pvt. Ltd., Mumbai) equipped with 13 mm cicula, flat and plain punches. Evaluation ests fo ablets he pepaed tablets of Aspaagus acemosus oot powde both by wet ganulation and diect compession wee subjected to standad quality contol tests fo tablets. Weight vaiation was detemined by weighing 20 tablets individually, the aveage weight was calculated and the pecent vaiation of each tablet was detemined. Hadness was detemined by taking 6 tablets fom each fomulation using a digital tablet hadness teste (Electolab Pvt. Ltd., India) and the aveage of applied pessue (Kg/cm 2 ) fo cushing the tablet was detemined. Fiability was detemined by fist weighing 10 tablets and placing them in a fiability teste (Electolab Pvt. Ltd., India), which was otated fo 4 min at 25 pm. Afte dusting, the total emaining weight of the tablets was ecoded and the pecent fiability was calculated. Disintegation time fo the tablets was detemined in 900 ml of distilled wate using a disintegation test appaatus (Electolab Pvt. Ltd., India). Results and Discussion Fundamental Powde Popeties he fundamental flow popeties of the Aspaagus acemosus oot powde exhibit no flow though funnel, which evealed that it was not upto the theoetical level fo pocessing into tablet dosage fom. Flow ate of diect compession fomulation and ganule evealed a significant impovement in the flowability (able 1). One of the most impotant factos affecting bulk density of a powde and its flow popeties, is the intepaticulate inteaction (Fohe., 1996). Desiable micomeitic popeties and the optimal pesence of wate diminish the cohesiveness of the powde, esulting in an inceased bulk density fo ganule and diect compession fomulation evealed enhanced flowability (Kohonen et al., 2002). Similaly, inceased tapped density fo ganule and diect compession fomulation indicated bette degee of compactibility as a function of applied pessue (Cason et al., 1994) (able 1). ue density value of powde and diect compession fomulation was quite close to each othe wheeas it was less in case of ganules.

4 132 Intenational Jounal of Phamaceutical Sciences and Nanotechnology Volume 1 Issue 2 July - Septembe 2008 Flow Popeties Plots of N/C vesus N (Kawakita plots) fo Aspaagus acemosus oot powde and fomulations, gave the linea elationship. Kawakita constants indicate the behavio of the powde fom the bulk density state to the tap density state. he constants of the Kawakita equation wee esolved fom the slope and intecept of the line fom gaphs N/C vesus N (able 2). Ganule densified the least (small compessible value) but attained the final packing state most slowly. On the othe hand, diect compession fomulation densified consideably but achieved the final packing state athe quickly than powde and ganule. Lowe value of a fo ganule evealed bette flowability than diect compession fomulation. Wheeas, lowe value of 1/b fo diect compession fomulation showed that it is less cohesive than ganule (Pesonen et al., 1986). Compaction Popeties Heckel Analysis he Heckel plots (Fig. 1) fo diect compession fomulation and ganule showed no lineaity at ealy stages of compession, because of paticle eaangement and the initial fagmentation. Ganule showed highest value fo die filling in initial stages of eaangement as indicated by thei intecept A values. hese featues of the late could esult to fomation of bidges and aches, which could in tun pevent close packing of the paticles in the bulk state. Highe value of A fo ganule implies highe degee of fagmentation. At low pessue, the lage ganules wee factued into small ones, which facilitated the futhe eaangement. When the compession pessue was inceased, the ganule showed plastic defomation (Ilkka et al., 1993). Geate slopes indicate a geate degee of plasticity of mateial. Mateials able 1 Fundamental powde chaacteistics*. Bulk Density (g/cm 3 ) ap Density (g/cm 3 ) ue Density (g/cm 3 ) Flow ate (g/sec) Powde (#85/100) ± ± ± ** Diect compession ± ± ± ± Ganule ± ± ± ± * All values ae expessed as mean ± SD, n=3 * Detemination not possible due to blocking of the funnel. able 2 Paametes of Heckel & Kawakita analysis. Equations Paametes Powde (#85/100) Diect compession Ganule Slope (K 10-2 ) Heckel Paamete Intecept (A) Yield Pessue (Py) Coefficient of Detemination ( 2 ) Compactibility (a) Kawakita Paamete Cohesiveness (1/b) Coefficient of Detemination ( 2 )

5 Nianjan Pata Ch et al. : A Systematic Study on Flowability 133 Fig. 1 Heckel plot fo Aspaagus oot powde (powde), diect compession fomulation (D.C) and wet ganulation fomulation (ganule) at vaious compession pessues (mean ± SD, n=3). Aspaagus acemosus oot powde was moe esistant to movement, once the initial phase of packing (as a esult of die filling) had been completed. his could be attibuted to the high cohesive foces likely to be pesent as a esult of its amophous natue. he mean yield pessue, Py, values wee found to be lowe fo Ganule. he esults theefoe indicated that ganule undewent plastic defomation moe easily and apidly than diect compession fomulation. his also confims that diect compession fomulation is somewhat esistant to defomation. Leuenbege Equation he compession susceptibility paamete (Fig. 2) fo compact fomed by diect compession and wet ganulation technique indicated that the maximum cushing stength is eached faste at lowe pessues of compession as opposed to Aspaagus acemosus oot powde. Highe value fo was obseved in case of ganule then diect compession fomulation. It showed that ganule can build a compact with a highe stength than diect compession fomulation. Lowe value of compession susceptibility fo Aspaagus acemosus oot powde demonstated that maximum tensile stength could be obtained slowly at highe pessue. he paamete and compession susceptibility allow a chaacteization of the diffeent mateials (Jetze et al., 1983). Low value fo a powde showed poo bonding popeties. In this egad Aspaagus acemosus fomulations showed modeate bonding popeties (able 3). In case of Aspaagus acemosus oot powde thee is an inceasing deviation of the diffeent values fo the adial cushing stength when a highe pessue of compession is applied, wheeas the cushing stength seem to emain constant independent of the inceasing pessue of compession in case of diect compession and wet ganulation. his cicumstance can be taken as a hint fo a capping tendency as with an inceasing compession pessue diffeent intenal tensions ae geneated, which can manifest diffeently when the cushing stength is detemined. his tendency could be confimed by the fact that it was not possible to poduce intact tablets at highe pessues of compession because of immediate capping in the die. Evaluation ests fo ablets All the batches of tablets wee poduced unde simila conditions to avoid pocessing vaiables. Weight vaiation fo the Aspaagus acemosus tablets pepaed by wet ganulation and diect compession method wee in the ange of 625 ± 16 mg and 624 ± 21 mg espectively. Hadness of tablets was highe fo tablets pepaed by wet ganulation method (5.2 ± 1.23 Kg/cm 2 ) then the diect compession method (4.8 ± 2.31 Kg/cm 2 ). he pecentage fiability fo tablets pepaed by diect compession method (0.75 ± 0.28 %) was moe than fo tablets pepaed by wet ganulation method (0.46 ± 0.16 %). he values of hadness test and pecent fiability indicated good handling popety of the pepaed Aspaagus acemosus oot tablets. Disintegation time was 10 ± 2.5 and 12 ± 1.5 min fo tablets pepaed by diect compession and wet ganulation methods espectively.

6 134 Intenational Jounal of Phamaceutical Sciences and Nanotechnology Volume 1 Issue 2 July - Septembe 2008 Fig. 2 he adial cushing stength was plotted against the poduct of the pessue of compession and the elative density Aspaagus acemosus oot powde (a), diect compession fomulation (b) and ganules (c). Fo evey pessue of compession thee compacts wee investigated (mean ± SD, n=3). able 3 Paametes of Leuenbege equation*. Compession Mateials susceptibility, γ (1/kg/cm 2 ) Maximum ensile Stength, (kg/cm 2 ) Powde (#85/100) ± ± Diect compession ± ± Ganule ± ± Conclusions Both wet ganulation and diect compession method could be used successfully fo developing tablet fomulation of Aspaagus acemosus oot powde. But ganules pepaed using met ganulation showed bette flowability, compessibility and compactibility compaed to diect compession fomulation. Hence, the pesent study ecommends the cuent needs to geneate simila data fo diffeent hebal dugs o Ayuvedic fomulations, which is highly essential in industial applications. Refeences Bhattachaya SK, Bhattachaya A, and Chakabati A. Adaptogenic activity of siotone a polyhebal fomulation of Ayuvedic asayanas. Indian J.Exp. Biol. 38: (2000). Cason JW, and Mainelli J. Chaacteize bulk solids to ensue smooth flow. Chem Eng. 4: (1994). Chopa RN, Chopa IC, Handa KL and Kapu LD. Indigenous dugs of India, Academic Publishes, Calcutta, 1994.

7 Nianjan Pata Ch et al. : A Systematic Study on Flowability 135 Dalvi SS, Nadkani PM, and Gupta KC. Effect of Aspaagus acemosus (Shatavai) on gastic emptying time in nomal healthy voluntees. J.Postgad.Med. 36: (1990). Esezobo S, and Pilpel N. Some fomulation factos affecting the tensile stength, disintegation and dissolution of uncoated oxytetacycline tablets. J Pham. Phamacol. 28: 8-16 (1976). Fohe C. Intepaticulate attaction mechanisms. In Aldebon G and Nystom C (eds.), Phamaceutical Powde Compaction echnology, Macel Dekke Inc, New Yok, 1996, pp Heckel RW. Density-pessue elationships in powde compaction. ans Met. 221: (1961). Ilkka J, and Paonen P. Pediction of the compession behavio of powde mixtues by the Heckel equation. Int J Pham. 94: (1993). Itiola OA. Compessional chaacteistics of thee staches and the mechanical popeties of thei tablets. Pham Wold J. 8: (1991). Jetze W, Leuenbege H, and Sucke H. he compessibility and compactibility of phamaceutical powdes. Pham. echnol. 7: (1983). Kasten H, and Kathaina MP. Evaluation of a new copocessed compound based on lactose and maize tach fo tablet fomulation. AAPS PhamaSciech. 6: Aticle 16 (2004). Kawakita K, and Ludde KH. Some consideations on powde compession equations. Powde echnology. 4: (1970/71). Kohonen O, Pohja S, Peltonen S, Suihko E, Vidgen M, Paonen P, and Ketolainen J. Effect of physical popeties fo stach acetate powdes on tableting. AAPS PhamSciech. 3: Aticle 34 (2002). Leuenbege H, and Rohea DB. Fundamentals of powde compession. 1. he compactibility and compessibility of Phamaceutical powdes. Pham. Res. 3: (1986). Oketch-Rabah HA. Phytochemical constituents of the genus aspaagus and thei biological activities. Hamdad. 41: (1998). Paonen P and Iilla J. Poosity-pessue function. In Aldebon G and Nystom C (eds.), Phamaceutical Powde Compaction echnology, Macel Dekke Inc, New Yok, 1996, pp Pesonen, and Paonen P. Evaluation of new cellulose mateial as a binding agent fo the diect compession of tablets. Dug Dev. Ind. Pham. 12: (1986). Rege NN, hatte UM, and Dahanuka SA. Adaptogenic popeties of six asayana hebs used in Ayuvedic Medicine. Phytothe Res. 13: (1999). Shileout G, Amold K, and Mulle G. Powde and mechanical popeties of micocystalline cellulose with diffeent degees of polymeization. AAPS PhamSciech. 3: Aticle 11 (2000). Yamashio M, Yuasa Y, and Kawakita K. An expeimental study on the elationships between compessibility, fluidity and cohesion of powde solids at small tapping numbes. Powde echnology. 34: (1983).