Pharma Times - Vol. 42 - No. 11 - November 2010 33 Introduction D r . D a l e W u r s t e r a t U n i v e r s i t y o f Wisconsin invented the wurster process wayb a c k i n 1 9 5 9 .

W u r s t e r p r o c e s s g a i n e d momentum in Indian Pharma Industry in therecent years because of the opportunities int h e g e n e r i c b u s i n e s s . A l m o s t a l l m a j o r companies are venturing into particle coatingin wurster. In addition, the process can bedone with same ease for both aqueous andn o n - a q u e o u s a p p l i c a t i o n s . T h e p r o c e s s parameters in the Fluid Beds are controllableprecisely, which ensures easier optimizationand reproducibility of the product quality.There are number of articles availableabout Wurster processing, optimization ands c a l e u p . S t i l l t h e s a m e m i s c o n c e p t i o n comes repeatedly that "whether the fluid bed process is linearly scalable?" Let us find outwhy even after 50 years of initial applicationstill same question is surfacing in the mindof R&D scientists. Also, let us try to find outthe factors and considerations for the scaleu p b a s e d o n a l l d y n a m i c s o f F l u i d B e d Processing.Currently FDA is focusing on the Qualityby Design concept where in one has to buildthe finished product quality attributes in thedesign itself. Can we build the quality in theproduct itself by designing the Formulationa n d P a r a m e t e r s s o t h a t o n e w i l l g e t consistent output of a process? Unless weunderstand the basics, it will be a difficulttask. Even to fill the QBR format, one mustk n o w h o w t o p r e d i c t t h e p a r a m e t e r s f o r c o m m e r c i a l s c a l e a n d t h e b a s i s f o r t h e predictions. W u r s t e r C o a t n i g S c a e l U p a n d S c a e l O u t Vasant Shetty*, Head - Process Technology & Customer Support, Pam Glatt Pharma Technologies Pvt Ltd.*E-mail : vasant.shetty@acg-world.com, prcess@acg-world.com A question always comes in mind "Whenthe scale up activity starts?" For any successful scale up activity, weneed a robust formulation with optimizedparameters. We need to optimize the processparameters in Lab scale by identifying thekey variables and their effect on the output.Unless these variables are identified and theimpact is understood, the scale up becomesvery painful activity. It is easy to understandthe variables in small scale and it requiresless time and cost. Once these variables arefrozen, we are left with only one unknownfactor - "mass effect" due to increase in thebatch weight from lab scale to commercialscale. Once the parameters are studied thenit will be easier to compensate the masse f f e c t b y d o i n g m i n o r c h a n g e s i n t h e predicted parameter in pilot and commerciall e v e l . T o h a v e b e t t e r o p t i m i z a t i o n t h e formulator must know about how "scale upmodel works.If the scale up activity starts at the stageof development itself then it will be very easyto scale up and scale out the formulation. P r o c e s s C o n s i d e r a t i o n s d u r i n g t h e product development L e t u s u n d e r s t a n d s o m e b a s i c considerations one has to look into duringthe formulation. Core particles In some cases, the variability starts fromthe core. An inert core pellets are used toload drug and subsequent functional coating.It can be drug core itself like extruded andspherodised product or drug layered pellets.A n y product development processn e e d s t o i n c l u d e i n - d e p t h s t u d y a n d c o n s i d e r a t i o n s o f P r o d u c t a n d p r o c e s s related variables. In many cases, w r o n g selection of the core or inconsistency in thec o r e o r c o a t i n g p o l y m e r l e a d s t o t h e variability from batch to batch.C o n t r o l l e d r e l e a s e p a t t e r n i s m a i n l y dependent upon the film thickness on thepellets. If the specification set for the core isn o t s t r i n g e n t e n o u g h a n d i f t h e averageparticle size of the core varies, even by50micron, this will lead to c o n s i d e r a b l e c h a n g e i n t h e f i l m t h i c k e n s w i t h s a m e percentage coating. For example, a mass ofabsolute spherical shape and having a means i z e 4 0 0 m i c r o n w i l l h a v e 1 4 % h i g h e r thickness in the film thickness compared tothe spheres of 350 micron. Similarly, thespheres of 800micron will have 7% thickerfilm than the spheres of 750micron. For thisreason, maintaining the specific surface areaw i t h i n v e r y n a r r o w m a r g i n f r o m l a b t o c o m m e r c i a l a n d b a t c h - t o - b a t c h i s v e r y critical.T o t a l s u r f a c e a r e a a v a i l a b l e f o r t h e c o a t i n g a l s o c h a n g e s a c c o r d i n g t o t h e surface roughness. The pellets with roughsurface will have considerably more surfacea r e a t h e n a p e l l e t w i t h s m o o t h s u r f a c e . Moreover, to cover the edges and crevicesof the rough pellets one has to make the filmthicker. In case of highly friable core as theattrition in the lab model is comparatively low,the surface remains to its original shape, butin pilot or commercial batch the core is beensubjected to higher attrition Fig3. It is verycritical to maintain the drug pellets as smoothas possible.In one case, the product temperaturein the drug loading stage changed during thes c a l e u p a c t i v i t y . W h e n t h e p r o d u c t temperature reduced from 60 to 35C, theoverall SR coating required to get the desiredrelease was reduced from 21% to 12% even Article Fig 1 - Diagram of Wurster Process 1Fig 2 - GPCG 1.1, Lab Model

Pharma Times - Vol. 42 - No. 11 - November 2010 34 though all parameters in the SR coating keptsame. This is mainly due to smooth surfaceof the drug pellets when processed at lowtemperature. W hen the drug loading wasdone at higher temperature, the surface of t h e d r u g - l o a d e d p e l l e t s w a s r o u g h a n d porous due to the spray drying effect Fig4.To cover these pores one has to apply morecoating. But when the drug loading was doneat lower temperature, the surface becamesmooth due to reduced spray drying andhigher moisture on the core surface.k e e p m o r e r i g o r o u s f l u i d i z a t i o n t o h a v e higher drying efficiency. One must keep inmind that the inlet air volume is not to drythe product, it has to be used to get therequired fluidization pattern. The requiredd r y i n g e f f i c i e n c y m u s t b e m a i n t a i n e d b y adjusting the temperature.Once the fluidization pattern is decidedand maintained in the lab model, for the scaleu p p r o c e s s t h e s a m e p a t t e r n m u s t b e maintained.For a highly water-soluble substrate, itis not recommended to keep high moisturein the initial stage. Static charge developso n l y o n c e t h e p e l l e t s a r e c o a t e d w i t h polymers. Therefore, the humidity can beincreased after initial coating. Fluidization Air Temperature: Theinlet air temperature is the last parameter tobe set as per the product requirement. It willdepend on the spray rate, type of solventmedia, tackiness of solution and have directi m p a c t o n t h e p r o d u c t h u m i d i t y a n d temperature. Batch Size: One has to use optimumbatch size for the development after initialf e a s i b i l i t y s t u d y . T h e u t i l i z a t i o n m u s t b e a b o v e 2 0 % o f w o r k i n g c a p a c i t y f o r n o n - functional coating and above 40% for thefunctional coating. Column Height: There is no basic ruleto set the column height. The height will varydepending on the particle properties. Shape,flow, Bulk Density, and size have impact ont h e f l o w b e h a v i o r . T h e c o l u m n m u s t n o t create barrier for the particle movement andat the same time, the air from the up bedzone must not be diverted towards down bed,which happens if the column height is toohigh or batch load is too low. Ideally, flows t u d y m u s t b e c o n d u c t e d t o c h e c k t h e m a x i m u m f l o w o f t h e m a t e r i a l i n s i d e t h e wurster column by fluidizing the mass andstopping the fluidization and measuring theheight of the bed inside and outside thecolumn. Spra y Rate: In the wurster typicallyb i n a r y n o z z l e a r e u s e d . T h e d r o p l e t formation, contact, spreading, coalescencea n d e v a p o r a t i o n h a p p e n a l m o s t simultaneously during the process Fig5. Theatomisation air used for the formation of spray mist also contributes to the evaporationwhich results in increase in the dropletsviscosity. Some time excessive atomisationair pressure leads to spray drying of portionof spray, especially in case of solvent basedc o a t i n g . T h e s p r a y r a t e d e p e n d s o n t h e s o l u t i o n p r o p e r t i e s a s w e l l a s t h e c o r e p a r t i c l e s . T h e s p r a y r a t e h a s t o b e s e t according to the drying efficiency, tackinessof the solution. To coat smaller particles weneed to keep the droplet size small to avoidagglomeration either by reducing he sprayr a t e o r i n c r e a s i n g t h e a t o m i s a t i o n s i r pressure. At the beginning of the coating, thes p r a y r a t e m u s t b e k e p t l o w t o a v o i d solublising the core or seepage of the drugor coating polymer in to other layer. Oncethe initial barrier formed the spray rate canbe primed up to the optimum level. It isevident that the as the particle becomesbigger it can take up more droplet withoutagglomerating. So normally, when the buildup is too high we may require to ramp up thespray rate in a regular interval. However, for Fig 3 - Effect of fluidization on Sugar Spheres 1Fig 4 - Effect of the Porous surface of core on the SR Film 1 U n c o a t e d c o r e p e l l e t S R c o a t e d c o r e p e l l e t Air Distribution Plate (ADP): One hasto select suitable base plate to get consistentfluidization at minimum attrition. The velocityand height gain is critical. The smaller particler e q u i r e s l e s s e r a i r v o l u m e t o a c h i e v e a c e r t a i n h e i g h t t h a n t h e b i g g e r p a r t i c l e s . Nevertheless, the air velocity or differentialpressure at the air distribution plate must bealmost same. Therefore, when we deal withsmaller particle to create the resistance atthe ADP to have better distribution of the air we have to use the plates having lesser opening area. This factor is very critical tohave more even airflow in all wurster in thecommercial models, where we have to dealwith multiple wursters. Fluidization Air Flow: Based on thep r o d u c t p r o p e r t y w e n e e d t o k e e p t h e fluidization. For a non-aqueous coating, abubbling type of fluidization in the down bedis recommended to minimize the particlefric tion and generation of static charges,whereas for aqueous application one can Fluidization Air Hum idit y: I n l e t a i r humidity is one of the most critical factorst h a t h a v e a n i m p a c t o n t h e productmovement as well as release

p r o f i l e . Although lower humidity in the air willenhance the drying capacity of the air evenat low temperature, it will cause excessivestatic charge in the product. The effect of thehigher or lower Humidity is unpredictable. For some the higher humidity may retard therelease, for other it may increase the release.The required specific or absolute humidityl e v e l m u s t b e s e t a t t h e i n i t i a l s t a g e o f development itself, to eliminate the staticcharges and process variability. Too highabsolute humidity will lead to depression inthe air temperature below the dew point,which will result in the condensation of water either on to machine or substrate surface.Once the inlet humidity is set then we havet o o p t i m i z e o t h e r p a r a m e t e r t o g e t t h e required release profile.

Pharma Times - Vol. 42 - No. 11 - November 2010 35 the functional coating as the size build is nott h a t s i g n i f i c a n t . O n l y t w o t o t h r e e s t a g e ramping is enough up to a build of 100%.This will also minimize the variation in theprocess.It is also critical to select proper sizetube in the pump. The peristaltic pump tendsto generate the pulse. Higher the pump RPMthe magnitude of the pulse is low. Therefore,we have to select smaller ID for the lower spray rate. Selection of Nozzle insert alsofollows same sequence. Smaller the nozzleinsert, more consistent will be the spray.However, here smaller insert may causenozzle chocking. Atomisation Air: It is always a question"How much atomisation air Pressure?" Canwe relate it to the spray rate?If the atomisation air pressure is highthen the mist size will be lower, then thec h a n c e s o f a g g l o m e r a t i o n w i l l a l s o l o w . However, if the set Atomisation air pressurein lab model is high, then the process willdemand too high pressure in pilot scale also.Excess pressure will lead to the particleshooting to the filter bag. The atomisation air must be adjusted to keep enough to avoidagglomeration. During the optimization of thes p r a y r a t e t o a c h i e v e f a s t e s t p o s s i b l e process, one has to keep the droplet verysmall. Higher the pressure smaller will bedroplet. It is also necessary to understandt h a t b e y o n d a c e r t a i n pressure the particle sizer e d u c t i o n w i l l b e negligible Fig6. Product Tempe-rature: I d e a l l y , t h e p r o d u c t t e m p e r a t u r e shall be kept at lowestpossible. It will dependon the Glass Transitiont e m p e r a t u r e f o r s o m e p o l y m e r . H o w e v e r , i n o t h e r c a s e s t o g e t maximum efficiency wehave to keep the productt e m p e r a t u r e a s l o w a s p o s s i b l e . L o w e r

t h e p r o d u c t t e m p e r a t u r e lesser will be the staticcharge generation but for some polymer likeHPMC we have to maintain high temperatureto minimize the agglomeration by drying of the film effectively. Apart from the above listed parameters,we have to optimize solution viscosity ands o l u t i o n c o n c e n t r a t i o n t o h a v e a b e t t e r control on the process. Higher the solutionviscosity or tackiness we have to reduce thespray rate. It is a common thinking that,higher solid content will reduce the processtime. However, this is completely wrong if thesolution is viscous and tackier in case of polymers like HPMC, Ethyl Cellulose whenthey are in solution form. As we increase thesolid content beyond certain limit for thesep o l y m e r s , t h e s p r a y r a t e w i l l r e d u c e drastically which results in higher processtime. If the viscosity of the solution is highthen it also makes the process more critical.So solution viscosity must be optimized tomake the process short and smooth. Design of Experiments: To optimisethe parameter and freeze the parameter onehas to do multiple trails. There are more than20 variables can be listed out in wurster process. Some of them are critical some arenot. Some parameters like batch size, sprayliquid viscosity, concentration, airflow, sprayassembly setting, base plate, column heightand dew point are easy to establish. Fix thesee a s y t o s e t p a r a m e t e r s a n d r e d u c e t h e number of variables. Perform some trail tofix some dependent variables likea t m a i r v o l u m e , e x h a u s t t e m p e r a t u r e a n d i n p r o c e s s moisture content etc.Finally do DOE to fix up mostcritical parameters like spray rate,atomisation air pressure/volume,p r o d u c t t e m p e r a t u r e a n d I n l e t t e m p e r a t u r e . T o m i n i m i z e t h e number of trials further one canuse statistical tools like Stavex.From the out put of the statisticalanalysis fix up the ranges for thep a r a m e t e r a n d v a l i d a t e t h e p r o c e s s t o c h e c k t h e r e p r o d u c i b i l i t y a n d freeze the parameter.Once the parameters are freezed at labmodel next step is predicting the parameter for scale up. Fig 6 -Atomisation Air Pressure vs. Droplet size chart Scale up: Second stage of the development issetting up parameters for the pilot model.Like lab model in the pilot model also havesingle wurster.T h e d e v e l o p m e n t o f t h e p r o d u c t i s normally done in 5", 6" or 7" wurster with thebatch size 1 to 3 kg. The wurster column andspray nozzle is small. Overall coating zoneis small. The recommended pilot model is18" wurster where the wurster column ismuch larger also the base plate Fig7. Fromthe lab to pilot although there is singe spraynozzle the nozzle is much bigger and canpermit higher spray rate. The batch depthand mass flow density increases. Overall, thec o a t i n g z o n e i n c r e a s e s f o r m l a b t o p i l o t scale. The overall coating zone will remainsame in pilot and commercial scale exceptthe height of the wurster column. All thep r o c e s s v a r i a b l e s a g a i n s h o w t h e i r s i g n i f i c a n c e i n s c a l e u p m o d e l a l s o . Nevertheless, once the effect of variables arestudied and understood in lab model it willmake the analysis much easier. Just like thevariables remaining same in pilot scale also,the same process control will apply. Only theunknown factor will be the mass effect.In many cases, one hears commentslike "When we scaled up the process we hadt o c h a n g e a l l p a r a m e t e r s . N o n e o f t h e predictions came true" or "the process timei s m u c h l o n g e r t h a n a n t i c i p a t e d " . I f o n e u n d e r s t a n d s t h e s c a l e u p p r i n c i p l e a n d applies them to predict the same for larger equipment, both this comment will not standtrue. As in the lab scale, one has to followsequential approach to set the parameter for the scale up. Any process starts with defining theb a t c h s i z e . T h e p r o c e s s p a r a m e t e r w i l l change slightly depending on the batch size. Fig 7 - 18" Wurster Fig 5 - Schematic diagram of Coating process

Pharma Times - Vol. 42 - No. 11 - November 2010 36 This is true here also just like nay other process. One has to set and validate theprocess for any change in the batch size.Keep the batch size within the recommendedo c c u p a n c y . F o r G P C G 1 . 1 , t h e w o r k i n g volume is 2.4 liter where as FBE 125 it is 84liter, i.e. 35 times. If some one wants to keepthe occupancy level same in pilot also thent h e b a t c h s i z e h a s t o b e i n c r e a s e d b y 35times.R e c o m m e n d e d w o r k i n g v o l u m e f o r non-functional coating is above 20% and for functional coating, it will be above 40% of the machine capacity.F o l l o w i n g e q u a t i o n c a n b e u s e d t o calculate the batch size. 2 B = V x D,w h e r e B = B a t c h s i z e i n k g V = R a t e d v o l u m e o f t h e product container D = U n t a p d e n s i t y o f t h e product in g/ccOnce the batch size is fixed, the nextwill be the base plate

selection. Here onecan refer to the base recommendations formthe machine supplier or they can fix up basedon the experience in the lab model. Air Flow Once the batch size is fixed, next is Air Flow. To fix up the airflow for pilot model onem u s t k n o w t h e a i r f l o w o r v e l o c i t y a t l a b model. From lab to pilot the face velocitymust be kept same. To maintain the samevelocity one must know the base plate areain lab and pilot model.In addition, it can be expressed in theterm of Fluidization Air Volume. Followinge q u a t i o n c a n b e u s e d t o c a l c u l a t e t h e Airflow. 2 V2 = V1 x A2 / A1,W h e r e V 2 = A i r F l o w f o r s c a l e u p modelV 1 = A i r f l o w a t L a b m o d e l A1 =Base Plate are for Lab Model A2 =Base Plate area for Pilot Model.Inlet air temperature and Humidity mustbe kept same as it in lab model Spray Rate: Many times, query comes stating that"Can I increase the spray rate in ratio to theincrease the batch size". The increase in thes p r a y r a t e s h a l l b e a l w a y s i n t h e l i n e o f increase in the drying capacity rather thant h e b a t c h s i z e . B e i n g s a i d t h e i n l e t a i r humidity and temperature will remain samefor the scale up model, the drying efficiencyis increased only it terms of air volume. Thespray rate can be increased in the same foldincrease in the inlet air volume.F o l l o w i n g e q u a t i o n c a n b e u s e d t o calculate to predict the spray rate in pilotmodel. 2 S2 = S1 x V2 / V1,W h e r e V 2 = A i r F l o w f o r s c a l e u p modelV 1 = A i r f l o w a t L a b m o d e l S1 =Spray Rate in Lab ModelS2 =Spray Rate in Pilot ModelFor example in the lab model if thespray rate is 15gm/minute for a batch size of 1.2kg and the fluidization airflow is 50 CFM.Then in 18" FBE 125, the airflow must beabout 650CFM and the spray rate shall be15 x 13 = 195gm/min for the batch size of 42kg.The increase in the spray rate must bec o m p e n s a t e d w i t h t h e i n c r e a s e i n t h e a t o m i s a t i o n a i r p r e s s u r e t o m a i n t a i n t h e droplet size of the spray mist. To keep thedroplet size same both in lab as well as pilotmodel one has to keep the spray rate toatomisation air volume same. It is possibleonly by measuring the air volumes in bothl a b m o d e l a n d s c a l e u p m o d e l . Manufacturers' manuals also can be usedFig 8.spray gun with higher capacity like HS guncan be used. Any deviation in the spray ratefrom the scale up factor of airflow shall bec o m p e n s a t e d b y e i t h e r i n c r e a s i n g o r reducing the inlet air temperature. Column Height: To fix up the columnheight, there are no factors, one has to adjustand keep the column height to get maximummass flow in the wurster column. The massflow study can be repeated here for differentbatch volume to fix up the gap. During thep r o c e s s , f r e q u e n t c h a n g e i n t h e c o l u m n height must be avoided. Even if it is required,it has to be adjusted at a fixed and minimuminterval for a process.By setting all these said parameters inthe pilot model, we left with one variable i.e.mass effect. There may be some deviationi n t h e r e s u l t s f o r m l a b s c a l e e v e n a f t e r maintaining the parameters as per the scaleup calculations due to mass effect. One or the other parameter may have to be changedmarginally to achieve desired release profile.The scale up activity starts with preliminarytrials with predicted parameter, analyze theresults, and take action if required to matchthe profile. If all the parameter and their effecton the release were understood in the labs c a l e , i t w i l l b e e a s i e r t o a n a l y z e t h e analytical results and vary the parametersto get desired profile. Process validation isrecommended to check the robustness of thep r o c e s s b e f o r e f i l i n g t h e p a r a m e t e r s o r planning the scale out activity. Scale Out: Once the development and scale upactivity completed systematically the scaleout will not lead to any surprises. From labto Pilot, the coating zone increased multifold.However, from pilot to production scale thecoating zone or wurster column diameter willremain same. The nozzle is same; the baseplate configuration will remain same. Theonly major change is increase in the number of wurster. There may be two to multiplew u r s t e r c o l u m n s d e p e n d i n g u p o n t h e machine capacity (Fig. 9). As the capacity of the machinei n c r e a s e s , t h e b a s e p l a t e d i a m e t e r w i l l increase so the base plate area. Here it isa g a i n s a m e c a l c u l a t i o n f o r t h e a i r f l o w calculation. Unless the commercial modelsare designed linearly, it is not possible toscale out the parameters from pilot. It hasbeen calculated adapted successfully somewell-known machinery manufacturer, whichmakes the scale out easier.For the scale out multiply the airflowagain in ratio of the base plate area andmaintain all other parameter like spray rateper gun, atomisation air pressure and producttemperature and humidity similar to the pilotFor example, the spray nozzle in GPCG1.1, consumes 1.2CFM of compressed air.When we scale up to 18" scale up model theair flow was increased as per the base plateration i.e. about 13 times and so the Sprayrate. To keep the atomisation air to spray rateration same the atomisation air needs toi n c r e a s e b y 1 3 t i m e s . T h a t m e a n s t h e atomisation airflow must be 1.2 x 13 = 15.6.To get same airflow in pilot and productionscale nozzle we need to keep about 4.4 bar pressure. Here as we increase the pressureo f t h e a t o m i s a t i o n a i r t h e v e l o c i t y a l s o increases and this is compensated by thelonger wurster column and longer expansionchamber.N o r m a l l y o n e s h o u l d r e s t r i c t t h e maximum pressure up to 4 to 5 bar. Higher the atomisation air pressure the mechanicalstress on the core will be high due to higher velocity. If some one uses higher air pressurein lab model then during the scale up either the spray rate needs to be reduced or the

Fig 8 - Atomisation air Pressure vs. Volumechart

Pharma Times - Vol. 42 - No. 11 - November 2010 37 model. Here very minute modification in theproduct temperature may require to nullifythe mass effect. Adjust the inlet temperaturei f r e q u i r e d t o m a i n t a i n t h e p r o d u c t temperature.I n t h e c o m m e r c i a l m o d e l , a g a i n t h e column height will depend on the batch sizeand one has to optimize the column heightfor the product by mass flow study duringthe 1st trial batch. Process time prediction: Based on the lab data, provided it hasbeen well, the process time for the pilot andcommercial scale can be predicted to thenear perfect. The prediction will be perfect if it is done from pilot to commercial.The batch size increased from lab toFBE 800C by 250 times but the spray timeo n l y b y 4 . 8 t i m e s . N e v e r t h e l e s s , b y using the HS sprayn o z z l e s s p r a y t i m e can be cut down to to 1/3. Summary: The scale up /s c a l e o u t a c t i v i t y must be the integralp a r t o f t h e d e v e l o p m e n t . I t i s wise to optimize andc o n t r o l t h e p r o d u c t q u a l i t y i n l a b s c a l e than in pilot scale. Allvariables need to bes t u d i e d i n t h e l a b scale by taking in tothe consideration of c o m m e r c i a l equipment. Theknowledge on t h e w o r k i n g o f commercial model ismust for a formulator.The process must bev a l i d a t e d f o r i t s r o b u s t n e s s i n t h e pilot scale at the 2nds t a g e o f development beforethe product filing.The scale up ism o r e c h a l l e n g i n g t h a n t h e s c a l e o u t . More the efforts putat the developmentallevel will reduce thehassles in scale upand scale out. Fig 9 - 32" Wurster Acknowledgement: D r . N o r b e r t P o l l i n g e r - T e c h n o l o g y Center Glatt, Binzen References: 1.Mr. David Jones, Factors to consider i n F l u i d B e d P r o c e s s i n g ; Pharmaceutical Technology Apr 19852 . D r . A t u l M . M e h t a , S c a l e u p c o n s i d e r a - t i o n s i n t h e f l u i d b e d p r o c e s s f o r C o n t r o l l e d R e l e a s e Product. Pharmaceutical TechnologyFeb 1988.Refer to the chart. Here the batch occupancy kept same in all models. A r e a L a b P i l o t P r o d u c t i o n M o d e l G P C G 1 . 1 F B E 1 2 5 C F B E 5 0 0 C F B E 8 0 0 C W o r k i n g V o l u m e l i t 2 . 4 8 4 3 6 7 5 9 7 N o . o f W u r s t e r 1 1 3 4 B a t

c h S i z e k g 1 . 5 5 2 . 5 2 2 9 3 7 3 S p r a y S o l u t i o n k g 2 . 7 9 4 . 5 4 1 2 . 2 6 7 1 . 4 S p r a y r a t e g / m i n 1 5 1 9 5 5 8 5 7 8 0 S p r a y t i m e 1 8 0 4 8 5 7 0 5 8 6 1 Advertisement Tariff for PharmaTimes New rates effective from 1/4/2008 P o s i t i o n s 4 C o l ( R s ) B / w ( R s ) Per insertion F r o n t C o v e r G a t e F o l d 6 0 , 0 0 0 . 0 0 B a c k C o v e r 4 4 , 0 0 0 . 0 0 I n s i d e F r o n t 3 0 , 0 0 0 . 0 0 I n s i d e B a c k 2 8 , 0 0 0 . 0 0 F i r s t P a g e ( P a g e 3 ) 3 0 , 0 0 0 . 0 0 L a s t P a g e ( O p p . I n s i d e B a c k ) 2 0 , 0 0 0 . 0 0 P a g e F a c i n g C o n t e n t & E d i t o r i a l N o t e . 2 0 , 0 0 0 . 0 0 D o u b l e S p a r e d ( O r C e n t e r S p r e a d ) 3 5 , 0 0 0 . 0 0 F u l l P a g e 1 6 , 0 0 0 . 0 0 1 0 , 0 0 0 . 0 0 H a l f p a g e 9 , 0 0 0 . 0 0 6 , 0 0 0 . 0 0 H a l f P a g e o n C o n t e n t P a g e 1 1 , 0 0 0 . 0 0 Q u a r t e r P a g e 5 , 0 0 0 . 0 0 3 , 5 0 0 . 0 0 1 t o 3 i n s e r t i o n D i s c o u n t 1 5 % 4 t o 6 i n s e r t i o n D i s c o u n t 2 0 % 7 t o 1 2 i n s e r t i o n D i s c o u n t 2 5 % For advertisements Mr. Ramesh Shah M/s. Kantilal N. Shah 702, Corporate House, Opp. Dinesh Hall, Income Tax, Ashram Road, Ahmedabad - 380009, GUJARAT.Ph : 07927540493, Fax : 079-30008999, Mobile : +91 93777 46368E-mail : kns_98@yahoo.com, kantilalnshah@gmail.comWebsite: www.knsmedia.com Payment advance for every issue in the name of "M/s. Kantilal N. Shah". 46" wurster