Pradnya Patil et al. IRJP 2012, 3 (1)INTERNATIONAL RESEARCH JOURNAL OF PHARMACYwww.irjponline.com ISSN 2230 8407Research ArticleAPPLICATION OF SPHERICAL AGGLOMERATION TECHNIQUE TO IMPROVEMICROMERITIC PROPERTIES AND DISSOLUTION CHARACTERISTICSOF NABUMETONEPradnya Patil*, V R M Gupta, R.H Udupi, B Sree Gir i Prasad, Nikunja Pati, K Sr ikanth,121222N Devanna, M Rama Devi32N.E.T Pharmacy College, Raichur, Karnataka, India1Pulla Reddy Institute of Pharmacy, Annaram (V), Hyderabad, Andhra Pradesh, India2H.O.D, Department of Chemistry, JNTU, Ananatapur, Andhra Pradesh, India3Article Received on: 01/11/11 Revised on: 2 1/12/11 Approved for publication: 09 /01/12*E-mail: pradnyapatil_4u @yahoo.co.inABSTRACTT he present work is aimed to enhance the solu bility and dissolution rate of Nabumetone,4-(6-methoxy -2-naphaleny l)-2-butano newater insoluble an ti-inflammatory dru g by spherical agg lomeration technique usin g a solvent change method consisting o f acetone, water and dichloromethane as solvent, nonsolvent an d bridging liquid respectively. The hydrophilic poly mers like poly vin yl pyrrolidone K-30 (PVP) and sodium alginate were used in theagglomeration pro cess. In frared (I.R) spectroscopic studies, Differential scanning calorimetery (DSC) and Scanning electron microscopy (SEM) were u sed forcharacterizatio n of pure dru g and its agglomerates. The I.R spectroscop y revealed that there is no chemical interaction between drug and polymers, alsoindicated that no chemical changes in the crystallized agglomerates .The agglomerates exhibited significantly improved solubility, dissolution rate andmicromeritic properties (angle o f repose, Carr s index,bu lk density,tap ped density.Hausner s ratio)compared with pure drug Nabu meton e. The aqueoussolubility and dissolutio n rate of the drug from spherical agglomerates was significan tly (p< 0.05) increased (nearly two times). SEM stu dies revealed that theagglomerates possess a go od spherical shape. The stud y revealed that Micromeritic Properties, Solu bility and Invitro drug release rate is increased withincrease in PVP concentration from 0.25 % to 1% as compared to sodium alginate.Keywords: Nabumeton e, agglomeration technique, solubility, dissolution rate, micromeritic properties.INTRODUCTIONspherical form.The technique had been used to improve the9Much research has been conducted in to methods ofpowder micromeritic properties (flowability andimproving drug solubility and dissolution rates to increase thecompressibility) and dissolution of drug. Then10, 11, 12oral bioavailability of hydrophobic drugs. Consequently,polymers were introduced in this system to modify their1many hydrophobic drugs show erratic and incompleterelease. The various parameters were optimized in this13, 14absorption from the gastrointestinal tract of animals andsuch as type, amount and mode of addition of bridging liquid,humans, which may lead to therapeutic failure. Thus, one oftemperature, agitation speed and reaction time to get morethe major challenges to drug development today is poorpractical yield of spherical agglomerates. General methods ofsolubility, as an estimated 40% of all newly developed drugsspherical crystallization are spherical agglomeration,are poorly soluble or insoluble in water. Also formulationemulsion solvent diffusion and ammonia diffusion method.2-5and manufacture of solid oral dosage forms and tablets inThe principle steps involved in the process of sphericalparticular have undergone rapid changes and developmentcrystallization are flocculation zone, zero growth zone, fastover the last several decades. The basic requirement forgrowth zone and constant size zone.Nabumetone is widely15commercial production of tablet is a particulate solid withused in the treatment of inflammation and pain associatedgood flowability, mechanical strength and compressibility.with rheumatic disorders such as rheumatoid arthritis,6Now a day s pharmaceutical industry prefers directosteoarthritis and also postoperative pains. It exhibits poorcompression technique because of its economical facility i nflow and compression characteristics and is hence a suitableprocessing without the need of moisture and heat with lesscandidate for spherical crystallization process to improve thenumber of processing steps. In direct tabletting method, it isflow properties and compressibility. To reach the valuable16necessary to increase flowability and compressibility of thegoal of improving the therapeutic efficacy of water insolublebulk powder in order to retain a steady supply of powderNSAID drug Nabumetone it is essential to improve themixture to the tabletting machine and sufficient mechanicalaqueous solubility of drug.strength of the compacted tablets. In addition to increasingEXPERIMENTAL7efficiency of the manufacturing process it is also important toMaterialsincrease bioavailability of the drug by improving theNabumetone was a gift sample from Devis Laboratories,solubility of the bulk drug powder. Among the variousHyderabad, India. PVP K-30 &Sodium alginate were8methods, spherical crystallization is a versatile process thatpurchased from S.D. Fine Chemicals, India. All otherenables to control the type and size of the crystals. Sphericalchemicals used were of analytical reagent grade.agglomeration is a size enlargement technique which is firstProcess development and optimizationdeveloped by Kawashima in 1986 and he has definedSpherical agglomerates of Nabumetone were prepared by thespherical crystallization as a novel agglomeration techniquesimple agglomeration technique using a three solvent systemby which both crystallization and agglomeration shall beon basis of miscibility of solvent and solubility of drugcarried out simultaneously in one step that can transforminvolving good solvent (acetone), a poor solvent (water) anddirectly the fine crystals produced in the crystallization into aa bridging liquid (dichloromethane). Here agglomerates werePage 156 Pradnya Patil et al. IRJP 2012, 3 (1)formulated using dichloromethane as bridging liquid whichmethod of crystallization was optimized and validatedhelps in binding of agglomerates by wetting the surface ofaccording to the study of variables.agglomerates. The spherical agglomerates were formed byMethod of preparation of agglomeratesaggregation of these dispersed crystals. In this study we usedIn this study, solvent change method was used for thethe hydrophilic polymers like sodium alginate and PVP topreparation of spherical crystals of Nabumetone. The drugprovide strength and sphericity to the agglomerates. It wasNabumetone (2gm) was dissolved inacetone(a good solvent)observed that PVP is more hydrophilic as compared toandhydrophilic polymers (PVP K-30 and Sodium alginate,sodium alginate in improving micromeritic properties which0.25 1%,m/V) in 100 ml distilled water.The drug solutionultimately increase the water solubility as well as in vitrowas added to a polymeric solution which was maintainedrelease.with continuous stirring at speed of 500 25 RPM. TheDesigning the spherical crystallization process requiresbridging liquid dichloromethane was added drop wise withoptimization of various process variables, which could affectmechanical stirring for 30 minutes. The spherical crystalsthe preparation and properties of the spherical crystals. Thewere collected by filtration and dried at room temperature for2hours.17Table - 1: Effect of variables on formulation of spherical agglomerates o f NabumetoneS.NO PARAMETERS VARIABLES OBSERVATION1 Bridgin g liquids Hexane No agglomeratesToluene lump formationDichloromethane Sp herical agglomeratesBenzen e No formation of agglomeratesChloroform lump formation2 Amount of bridging liquid (ml) < 2.8 No agglomeration2 .8 Sp herical agglomerates> 2.8 Irregular shaped agglomerates3 Agitation speed(rpm)3 00No agglomeration4 00 Sp herical but large agglomerates5 00 Sp herical agglomerates6 00 Irregular but small shaped agglomerates7 00 Irregular but small shaped agglomerates4 Agitation time (min) 5 No Spherical agglomerates15 In complete agglomerates30 Sp herical agglomeratesCHARACTERIZATIONvolumetric flask filled with water and 2% SLS. TheIR, DSC & SEM Studiesvolumetric flasks were shaken for 2 h on mechanical shaker.The infrared (IR) spectra of powder Nabumetone, physicalThe solution was filtered through Whatmann filter paper No.mixture and the agglomerates were recorded on an IR-1 and the drug concentration was determinedspectrophotometer (FTIR 8300, Shimadzu, Japan) by the KBrspectrophotometrically at 271 nm. Each sample was done inpellet technique. Differential scanning calorimetry (DSC)triplicate.analysis was performed using a DSC-60 calorimeterIn vitro Dissolution Studies(Shimadzu).The surface morphology of the agglomerates wasThein vitrodissolution studies were carried out using 8assessed by scanning electron microscopy (SEM) (Leicastations USP 23 dissolution testing apparatus (Electro lab,StereoScan 430, LEO, UK).India). The dissolution medium used was 900 ml of 2%,m/vMicromeritic Propertiessodiumlaurylsulphate (SLS). The agglomerates containingThe loose bulk density (LBD) and tapped bulk density (TBD)500 mg of Nabumetone were weighed and filled into a hardof pure drug Nabumetone and its spherical crystals weregelatin capsule. In the case of pure drug, 500 mg of puredetermined using measuring cylinder method. Carr s indexNabumetone was weighed and filled into a capsule. Thewas calculated using LBD and TBD values.The angle ofcapsule was then introduced into the dissolution medium. The18repose was assessed by the fixed funnel method. A knownmedium was stirred at 75 rpm using a paddle at 37 0.5 C.19amount of agglomerates was allowed to flow through aThe samples were collect ed and analyzedfunnel fixed at a constant height (h).The height (h) andspectrophotometrically.diameter (2r) of the pile of powder were measured toStatistical analysiscalculate the angle of repose as tan =h/r.The results were analyzed by two tailed Student st-test usingDrug Loading Efficiencythe Graph Pad Instat Software (GPIS; Version: 1.13). The20The drug loading efficiency of crystals was determined bymean dissolution time (MDT) was calculated using the Origindissolving 100 mg of crystals in 100 ml of methanol,software.followed by measuring the absorbance of appropriatelyRESULTS AND DISCUSSIONdiluted solution spectrophotometrically (PharmaSpec UV-IR Studies1700, UV-Visible Shimadzu) at 271 nm.The interaction between the drug and the polymer wasSolubility Studiesstudied by IR spectroscopy and DSC. The IR peaks of pureThe solubility of nabumetone spherical agglomerates in waterdrug Nabumetone, physical mixture and sphericaland 2% SLS was determined by taking excess quantity ofagglomerates are shown in Fig 1 and Table1. IR spectra ofspherical agglomerates and adding to screw-capped 50 ml ofNabumetone showed characteristics peaks at 3062 cm-Page 157 Pradnya Patil et al. IRJP 2012, 3 (1)(aromatic C-H stretching),2956&2848 cm, 2916 & 2812Scanning Electron Microscopy Studies1-1cm(C-H stretching of CH-O-CHand CHgroupsPhysical characterization of agglomerates can be done by-1332asymmetric and symmetric resp.) ,1705 cmSEM analysis t o assess typical shape of agglomerates and-1(C=O),1634,1608,1505&1485 cm(C=C ringuntreated drug. The spherical single agglomerate is formed-1stretching),1452&1387cm, 1410&1363cm(C-H bendingby closel y compacted fine rectangular shaped crystals which-1-1of CH,OCH,&CHgroups asymmetric and symmetric) ,give evidence of enlargement of crystal surface of3321028cm(C-O-C) ,957,895,845cm(fused and substitutedNabumetone leading to increase flowability and compression-1- 1aryl rings).The comparison of IR spectra of pure drug,property. The surface morphology of prepared agglomeratesphysical mixture of drug and polymer along with that ofwith 1% PVP and polymer is shown in figure 4. (36X) andspherical agglomerates of Nabumetone (NA-P-4) reveals thatfigure 4 (160X) of D, E, F. and also spherical agglomeratesthere is no change in position of characteristic absorptionof Nabumetone shown figure 4 figure 4 (100X, B) werebands. This suggests that the drug has not undergonespherical but no sphericity and smooth surface. The SEMinteraction with pol ymer (sodium alginate, PVP K 30) andanalysis showed that the prepared agglomerates wereother excipients.spherical in shape with smooth and regular surface.DSC StudiesMicromeritic PropertiesDSC thermograms were shown in Fig 2 for pure drugThe results of loose bulk density (LBD) and tapped bulkNabumetone and polymers PVP K30 & Sodium Alginate.density (TBD) are presented in Table - 2. These parametersThe DSC study indicates that there is no appreciable changewere used to assess the packability of the crystals. The purein the nature of thermo grams. The pure drug showed sharpdrug powder was more bulky and fluffy, which was indicatedendothermic peak with highest peak area at a melting point ofby the lowest LBD value (0.184 0.00058 gmL-1,n=3).The81.13c, which is in agreement with the literature M.P. Thehighest TBD value (0.278 0.001gmL-1,n=3)of pure drug0DSC thermogram of the formulation of spherical agglomerateindicates a high intergranular space between particles. Inof Nabumetone with PVP K30 and sodium alginate showedcontrast, the spherical agglomerates exhibited higher LBDendothermic peaks with comparatively reduced areas at(0.231 0.0015 to 0.253 0.0005 gmL-1,n=3) and TBDmelting point of 79.82c and 79.68c. The lowering of m.p(0.247 0.00057 to 0.277 0.00058gmL-1,n=3)values. These00shows that change may be due t o crystallization of drug withresults indicate good packability of the prepared sphericalsolvent acetone. As there is no much change in the thermalcrystals when compared with pure Nabumetone.behavior of the drug and its formulations as indicated by theThe results of Carr s index, Hausner s ratio and angle ofthermo grams, it can be concluded that the drug has retainedrepose of spherical crystals in comparison with pure drug areits identity even in formulations and indicates there is nopresented in Table - 2. These parameters were used to assessinteraction between the drug and polymers used in the presentthe flow and compressibility properties of the agglomerates.study.Carr s index and Hausner s ratio of pure drug wereXRD Studies33.57 0.0058% and 1.50 0.0058(n =3),respectivel y,X-ray powder diffractometry (XRPD) is a powerful techniqueindicating extremely poor flow properties. The powder couldfor the identification of crystalline solid phases. Everynot pass through the funnel during the angle of reposecrystalline solid phase has a unique XRPD pattern, which canexperiment. The poor flow of Nabumetone could be due toform the basis for its identification. The X-ray powderthe irregular shape and high fineness of the powder, whichdiffraction pattern in the range 2 -50 showed in Fig 3, thatposed hurdles in the uniform flow from the funnel. On thethe characteristic diffraction peaks of Nabumetone whichother hand, all the prepared spherical agglomerates exhibitedwere still detectable in the crystallized samples, suggestinglow Carr s index, Hausner s ratio and angle of repose values,that the particles get crystallized in the presence of sodiumindicating excellent flow properties and compressibilityalginate and PVP-k-30 did not undergo any structural(Carr s index: 5.70 0.0153 to 9.88 0.005%,n=3: Hausner smodifications. However, the differences in the relativeratio:1.07 0.01 to 1.11 0.005,n=3;angle of repose:23.02intensities of their peaks are due to the differences in the0.27 to 27.09 0.0058o,n=3). Similarly the sphericalcrystallinity of particle size of the samples and decrease inagglomerates of Nabumetone prepared without polymer (SP)the intensities may be due to change in sphericity. It is veryexhibited low Carr s index, Hausner s ratio and angle ofdifficult to identify the presence of sodium alginate or PVP-repose values, indicating excellent flow properties andk-30 in XRPD spectra as they are pol ymers with amorphouscompressibility (carr s index:10.5 0.0058%,n=3; Hausner sstructure and therefore no Sharp peaks are apparent atratio:1.11 0.0058,n=3;angle of repose:28.49 0.015o,n=3).particular 2 due to the very low crystallinity of theThe improved flowability and compressibility of sphericalcomponents in the form of spherical agglomerates.agglomerates may be due to the sphericity, regular and largersize of crystals. Among all the prepared spherical crystals,)the agglomerates prepared with 1%,m/V, PVP exhibitedgood micromeritic properties .Page 158 Pradnya Patil et al. IRJP 2012, 3 (1)Table 2: Micromeritic properties of agglomerates and pure drugaSphericalLBDTBDCarr s indexHausner sAngle ofParticle Sizecrystals(g mL 1)(g mL 1)(%)ratiorepose ( )( m)bbbbbNS10.253 0.0010.2760.188.33 0.011.09 0.0125.640.13199 .5 2 0.12218 .7 7 0.11bbbbbNS20.237 0 .0 0150.2630.000589.880.011.11 0.00527.09 0 .0 058bbbbbNS30.253 0.00050.2770.000588.660.021.09 0.00526.56 0 .0 099 239 .8 8 0.10bbbbbNS40.237 0.00050.2630.0019.880.0051.11 0.00526.86 0.005 251 .1 8 0.12bbbbbNP10.241 0 .0 0050.2580.001536.590.00581.07 0.00524.75 0.01 208 .1 2 0.13b229 .0 8 0.15NP20.231 0.0015b0.2470.0005b6.48 0.01b1.07 0.01b24.57 0.12257 .0 3 0.11bbbbbNP30.231 0.0010.2470.000576.480.015281.07 0.0123.62 0.02bbbbbNP40.248 0.001520.2630.0015.700.01531.07 0.015223.02 0.27 263 .0 2 0.10b87.09 0.12bbbDRUG0.184 0.000580 .2 78 0.001 33.57 0 .0 0581.5 0.0058-----bbbbbSP0.247 0.000570.276 0.0005810.5 0.00581.11 0.005828.49 0.015 131 .8 2 0.22LBD loose bulk den sity, TBD tapped bulk density.a Mean SEM,n= 3.b Significantly different compared to pure Nabumetone (p< 0 .0 5).Drug loading and solubility studiesThe results of drug loading efficiency and aqueous solubility are shown in Table - 3. The drug loading efficiency of sphericalagglomerates is in the range 93.7 2.3 to 98.6 1.3 (n= 3), indicating negligible loss of drug during the crystallizationprocess. The results of solubility studies indicate that pure Nabumetone possesses a very low solubility in water (2.43 1.1 gmL,n= 3) while as in 2% SLS shows (438 1.3 g mL,n= 3) because of its surfactant property. Solubility of spherical11agglomerates without polymer showed (3.1 1.2 g mL,n= 3) where as in 2% SLS showed (582.2 1.1 g mL,n= 3).11However the drug solubility from the Spherical Agglomerates increased significantly (p< 0.05), demonstrating that theincorporation of Sodium Alginate and PVP K30 as polymers in different concentrations enhances the drug solubility in wateras well as in 2% SLS from (5.37 1.2; 617.8 1.1 g mL,n= 3) to (7.64 1.1; 831.1 1.2 g mL,n= 3) by improving11wettability. Maximum solubility from spherical agglomerates was observed at 1% (m/V) PVP-K30 (7.64 1.1 g mL,n=13). Similar results were observed with 2% (m/V) SLS (Table - 3).Table - 3: Drug lo ading efficiency and Solubility data for the Agg lomerates and Pure drugab1Spherical crystalsDrug loading (% )So lubility ( g mL)WaterSLS( gm/ml)(2% ,m/V)98.21.2ccNS15.37 1 .2617.8 1.196.01.3NS25.42 1 .0c631.1 1.5c94.61.35.73 1 .4c648.9 1.3cNS394.21.2ccNS45.82 1 .5657.8 1.198.71.3ccNP17.33 1 .8804.4 1.597.31.1NP27.46 1 .6c813.3 0.5c95.51.27.51 1 .3c823.2 1.3cNP393.72.3ccNP47.64 1 .1831.1 1.2100 0.0DRUG438.2 1.32.43 1 .193.3 1.3ccSP582.2 1.13.1 1.2a Mean SEM,n= 3.b Drug loading is expressed as % or mg of drug per 100 mg of cry stals.c Significantly different compared to pure Nabumetone (p< 0.05).In Vitro Evaluationshowed increased dissolution rate in 2% SLS with increase inThe results ofin vitrodissolution studies are shown in Fig. 5sodium alginate and PVP concentration in range of (76.966and Table 5. Pure drug Nabumetone exhibited less release at0.2, n=3) to(96.440.2,n= 3) with MDT (14.22 0.30the end of 180 min in 2% SLS (69.880.2%,n= 3) withmin, n=3) to (13.16 0.30 min, n=3); but the meanMDT14.470.30 min, n=3.Dissolution rate of Nabumetonedissolution time (MDT) of spherical agglomerates containingSpherical agglomerates in 2%SLS was (71.5810.2%,n=1.0% PVP was low when compared to that of pure drug in3) with MDT (13.68 0.30 min, n=3). Spherical agglomerates2% SLS (11.10 0.30 min, n=3). This could be due toPage 159 Pradnya Patil et al. IRJP 2012, 3 (1)increased wettability of the drug by the presence of PVP.4)Kamble R, Maheshwari M, Paradkar AR and Kadam S .Melt solidificationThis might be due to the surfactant property of SLS on thetechnique: Incorporation of higher wax content in ibu profen beads. AAPSPharmSciTech. 2004; 5(4): Article 6.drug which shows maximum dissolution of drug within 1205) Kapsi SG , Ayres JW. Processing factors in development of solid solutionmin. The mechanism behind the solubility and dissolutionformulation of itraconazole for enhancement of drug dissolution andrate enhancing effect of Nabumetone in crystal form maybioavailability. Int. J. Pharm. 2001; 229:19 3-203.resemble the solid dispersion mechanism despite the large6) M.M.Gupta,B. Srivastava, Monika Sharma, Vinita Arya.Sphericalcrystallization: a tool of particle engineering for making drug powderparticle size of the crystals. This effect may be due t osuitable for direct compression. International Journal of Pharma Researchimproved wettability of the surface of crystals by theand Development.2010; 12(1):1-10.adsorption of PVP onto the surfaces of crystals. They also217) Shangraw, R.F, Compressed Tablets by Direct Compression. Indemonstrate that PVP is a suitable polymer for thepharmaceutical Dosag e Form: Tablets, Lieberman, H. A., L. Lachman andJ.B. Schwartz (Eds). Marcel Dekker, New York Vol. 1, 1989; 195-246.preparation of spherical agglomerates of Nabumetone.8) Gharaei-Fathabad, E., Biosurfactants in pharmaceutical industry: A mini-aTable 4 . Drug release and MDTreview. AM. J. Drug Discovery Dev 2011; 1: 5 8-69.SphericalSLS (2%,m/V)9) Kawashima Y., Ok umura M. and Takenaka H.Spherical cry stallization:Agglomeratesdirect spherical agglomeration of salicylic acid crystals duringNabumetone ReleasedMDT (min)crystallization. Science, 1982; 216: 1127-1128.(% )10) Kawashima, Y. Development of spherical crystallization tech nique andbNS11 00.0 0.0 (after 3h)16.58 0.21its application to pharmaceutical system. Arch. Pharm. Res 1984; 7: 145-bNS21 00.0 0.0 (after 3h)15.81 0.11151.NS31 00.0 0.0 (after 3h)14.22 0.35b11) Kawashima Y, Cui F, Takeuchi H, Niwa T, Hin o T, Kiuchi K.bNS41 00.0 0.0 (after 3h)13.13 0.10Improvements in flowability and compressibility of pharmaceutical cry stalsbNP11 00.0 0.0 (after 3h)13.91 0.11for direct tabletting by spherical crystallization with a two solvent system,NP21 00.0 0.0 (after 3h)13.44 0.30bPowder Technology 199 4; 78: 151-157.bNP31 00.0 0.0 (after 3h)13.16 0.3112) Bodmeier R, Paeratakul R. Sph erical agglomerates of water-insolublebNP41 00.0 0.0 (after 2h)11.10 0.16drugs, J Pharm Sci 1 989; 78: 964-967.1 00.0 0.0 (after 3h)14.47 0.29bDRUG13) Di Martino P, Barthelemy C, Piva F, Joiris E, Palmieri GF, Martelli S.bSP1 00.0 0.0 (after 3h)13.68 0.11Improved dissolution behav ior of fenbufen by spherical crystallization, DrugMDT mean dissolution time.Dev Ind Pharm 1 999; 25: 1073-1081.a Mean SEM,n= 3.14) Sano A, Kuriki T, Kawashima Y, Takeuchi H, Hino T, Niwa T. Particleb Significantly different compared to pure Nabumetone (p< 0.05 ).design of tolbutamide by spherical crystallization tech nique. IV,Improvement of dissolution and bioavailability of direct compression tabletsCONCLUSIONprepared using tolbutamide agglomerated cry stals,Chem .Pharm.Bull 1 992;40: 3030-3035.The present study shows that spherical agglomerates of15) Yadav A.V, Designing of pharmaceuticals to improve physicochemicalNabumetone prepared with PVP exhibited improvedproperties by spherical crystallizatio n technique, Jou rnal of Pharmacymicromeritic properties which are essential requirement forResearch. Oct-December 2008; 1(2): 105-1 12.direct tableting. Hence in addition to improving the solubility16) Kulkarni P.K; Subash Chandra Bose .P, Spherical Agglomerates ofNabumetone, Indian Journal of Pharmceutical Education and Research Jan-enhanced dissolution rate was observed compared to puremar 2007; 41 (1):18.drug Nabumetone. So this technique may be applied for17) Chorasia M. K. Preparation and characterisation of agglomeratedproducing oral solid dosage forms of Nabumetone withspherical crystals of ibuprofen. Indian Journal of Pharmaceutical Science,improved dissolution rate and oral bioavailability.2007; 364-368.18) J. Wells, Pharmaceutical preformulation, the physicochemical propertiesREFERENCESof drug substances, in Pharmaceutics th e Science of Do sage Form Design,1 )Mudit dixit, Parthasarathi Kulkarni, Vangala Gowtham, H G Shivkumar,2nd ed. (Ed. M. E. Aulton), Churchill Living stone, London 2002; 113 1 38.Preparation and characterization of spray dried microparticle and chilled19) A. Martin, P. Bustamante and A. Chun, Micromeritics, in Physicalspray dried particle of keto profen by spray drying method Asian Jou rnal ofPharmacy Physical Chemical Principles in the Pharmaceutical Sciences,Pharmaceutical and Clinical Research 2011;4(1):138-142 .4th ed., Lippincott Williams and Wilkins, Baltimore 2002; 423 4 52.2 ) Corrigan DO, Corrigan OI and Healy AM Predicting the physical state of20)S. Mutalik and N. Udupa, Pharmacological evaluation of membranespray dried composites: salbutamol sulphate/lactose and salbutamolmoderated transdermal sy stem of glipizide, Clin. Exp. Pharmacol. Physiol.sulphate/polyethylene glycol co -spray dried systems. Int. J. Pharm.2004;1 2, 2006; 17 26.2 73: 171-1 82.21)S. Kawashima, T. Handa, H. Takenchi, M. Okumura, H. Katou and O.3 ) Craig DQM The mechanisms of drug release from solid dispersions inNagai, Crystal modification of phenytoin with polyethylene glycol forwater-soluble polymers. Int. J. Pharm. 200 2; 231: 131-144.improving mechanical strength, dissolu tion rate and bio-availability by aspherical crystallization techniqu e, Chem. Pharm. Bu ll. 1986; 34: 33763383.Page 160 Pradnya Patil et al. IRJP 2012, 3 (1)Fig 1: Photographs showing effect of process variables on Ag glomeratio n (A) Lump formatio n (B) Spherical agglo merates(C) Irregular shapedagglomerates (D) Spherical ag glomerates (E)Spherical but large agglomerates (F) In co mplete agglomeratesFig 2: IR Spectra of (A) Pure drug Nabumetone; (B) Spherical agglomerate of Nabumetone; (C) Nabumetone Spherical agg lomerate with PVPpolymer; (D) Nabumetone Spherical agglomerate with Sodium alginate polymer.Fig 3:DSC Thermograms of (A) Nabumeto ne, Pure drug (B) spherical agglomerates of Nabumeto ne, (C) Na bumetone Spherical ag glomerates withPVP po lymer (D) Nabumetone Spherical agg lomerates with sodium alginate polymerPage 161 Pradnya Patil et al. IRJP 2012, 3 (1)Fig 4: XRD analysis of (A) Pure drug Nabumetone; (B) PVP K-30 Spherical agglomerates of Nabumetone; (C) Sodium alginate sphericalagglomerates of NabumetoneFig 5: SEM analysis of A) Nabumetone pure drug; B)Spherical agglomerate of Nabumetone of 1 00magnification; (C,D,E,) Spherical agglomerateXof Nabumetone with polymer 1% PVP k-30 with magnification 135x, 36x,160xFig 5:Cu mulative Percent Drug Release of(A)Sodium Alg inate Nabu metone Spherical Agglomerates in different concentrations with pure drug and Plainagglomerates;(B)PVP Nabumetone spherical agglomerates in different concentrations with pure drug and Plain agglomerates;(C)1% PVP and sodiumalginate Nabumetone spherical agglomerates with pure drug and Plain agglomeratesSource of support: Nil, Co nflict of interest: None DeclaredPage 162