Controlling Particle Size and Release Properties - American Chemical

Chapter 17

Controlling Particle Size and Release Properties Secondary Processing Techniques

Downloaded by UNIV OF PITTSBURGH on December 18, 2014 | http://pubs.acs.org Publication Date: May 31, 1988 | doi: 10.1021/bk-1988-0370.ch017

David M. Jones International Process Technology Development, Glatt Air Techniques, Inc., 20 Spear Road, Ramsey, NJ 07446

Secondary processing techniques are often required to optimize the functional properties of a material or to create a new product. Examples include but may not be limited to drying, dedusting, particle size enlargement to enhance dispersability, or coating to provide protection or some type of functional release. Batch type fluidized bed processing readily lends itself to these forms. Developed more than 30 years ago to improve drying efficiency, primarily in the pharmaceutical industry, the system has evolved into a highly effective and controllable technology for many applications. Its chief limitation is volume capability. Because it handles material on a batch basis, throughput is far less than in continuous fluidized beds. This is not a problem in the pharmaceutical industry, which is the largest user, because handling products in batches is desired from perspectives of quality control and cost (many active drugs cost in excess of $100/kg). In the food and chemical industries, high volume products generally prohibit the use of this technology. However, specialty type products involving expensive components and very precise processing are ideal candidates for the batch fluid bed process. Equipment and Process

Description

F l u i d i z e d Bed Dryers I n o r d e r t o i l l u m i n a t e t h e p o s s i b i l i t i e s , i t i s h e l p f u l t o have a n u n d e r s t a n d i n g o f t h e c h a r a c t e r i s t i c s o f t h i s t e c h n o l o g y . As mentioned p r e v i o u s l y , f l u i d i z e d b e d p r o c e s s i n g s t a r t e d s i m p l y a s d r y i n g ( i l l u s t r a t e d i n f i g u r e 1 ) . Many g r a n u l a t i o n p r o c e s s e s i n v o l v e d wet massing i n a h i g h o r l o w s h e a r m i x e r a n d subsequent t r a y d r y i n g . Depending on t h e t y p e o f p r o d u c t , t h e t r a y d r y i n g p r o c e s s c o u l d t a k e a s l o n g a s 24 h o u r s . The b e n e f i t s o f f l u i d b e d d r y i n g were o b v i o u s because t h e p a r t i c l e s were f l u i d i z e d b y t h e d r y i n g media w h i c h reduced d r y i n g t i m e o f t e n t o l e s s t h a n one hour. The damp g r a n u l a t i o n i s t r a n s f e r r e d t o t h e p r o d u c t c o n t a i n e r which i s c y l i n d r i c a l o r s l i g h t l y c o n i c a l and h a s a s c r e e n , a n d gas o r a i r d i s t r i b u t o r p l a t e a t i t s base. The p r o d u c t

c

0097-6156/88/0370-0158$06.00/0 1988 American Chemical Society

In Flavor Encapsulation; Risch, S., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1988.

17. JONES

Controlling Particle Size & Release Properties

159


c o n t a i n e r i s t h e n p l a c e d i n t h e machine a n d h e a t e d a i r drawn t h r o u g h t o f l u i d i z e t h e m a t e r i a l and c a r r y away t h e e v a p o r a t e d m o i s t u r e . The c y l i n d r i c a l space above t h e p r o d u c t c o n t a i n e r a c t s a s a d e c e l l e r a t i o n zone o r e x p a n s i o n chamber. I n t h e space above t h i s chamber, a f i l t e r i s used t o s e p a r a t e t h e p r o d u c t from t h e a i r stream. D u r i n g f l u i d i z a t i o n a n d d r y i n g , f i n e s c o l l e c t i n t h e f i l t e r r e d u c i n g a i r volume and p o s s i b l y d r y i n g e f f i c i e n c y ( d e c r e a s i n g w a t e r removal r a t e ) . P e r i o d i c a l l y , f l u i d i z a t i o n must be i n t e r r u p t e d b y s t o p p i n g a i r f l o w t o shake f i n e s o u t o f t h e f i l t e r a n d back i n t o t h e batch. F l u i d i z e d B e d G r a n u l a t i o n The n e x t e v o l u t i o n was t o p o s i t i o n a n o z z l e i n t h e e x p a n s i o n chamber, t o s p r a y a w a t e r o r b i n d i n g medium downward i n t o t h e d r y f l u i d i z i n g powders ( f i g u r e 2 ) . By i n c o r p o r a t i n g a v a r i e t y o f process c o n t r o l s , g r a n u l a t i o n o r a g g l o m e r a t i o n was f e a s i b l e . F l u i d i z e d Bed Top Spray Coater F i l m c o a t i n g i s v e r y s i m i l a r t o g r a n u l a t i o n using a f i l m forming binder. S l i g h t l y d i f f e r e n t p r o c e s s i n g c o n d i t i o n s and some equipment m o d i f i c a t i o n s y i e l d t h e a b i l i t y t o a p p l y f i l m s o r m o l t e n m a t e r i a l s t o a wide range o f p a r t i c l e s i z e s . The diagram i n f i g u r e 3 shows t h e m o d i f i c a t i o n s t o a c o n v e n t i o n a l g r a n u l a t o r w h i c h would f a c i l i t a t e t o p s p r a y c o a t i n g . A primary d i f f e r e n c e i s that a higher f l u i d i z a t i o n v e l o c i t y i s d e s i r e d r e s u l t i n g i n t h e need f o r a n expanded d e c e l e r a t i o n zone, hence t h e extended c o n i c a l e x p a n s i o n chamber. A d d i t i o n a l l y , c o n t i n u o u s f l u i d i z a t i o n i s d e s i r e a b l e from b o t h e c o n o m i c a l a n d f u n c t i o n a l p o i n t s o f view. F o r t h i s reason, t h e f i l t e r housing i s e n l a r g e d and d e s i g n e d t o shake f i n e s back i n t o t h e b a t c h w i t h o u t stopping f l u i d i z a t i o n o r spraying. F l u i d i z e d Bed Wurster Coater Almost s i m u l t a n e o u s l y w i t h t h e development o f c o n v e n t i o n a l f l u i d b e d g r a n u l a t i o n , work was b e i n g c o n d u c t e d on t h e c o a t i n g o f m a t e r i a l s r a n g i n g from powders t o t a b l e t s . The W u r s t e r system, i l l u s t r a t e d i n f i g u r e 4, was i n v e n t e d more t h a n 20 y e a r s ago b y Dr. D a l e W u r s t e r ( 1 ) , t h e n a p r o f e s s o r a t the U n i v e r s i t y o f W i s c o n s i n . The c o a t i n g chamber w h i c h i s g e n e r a l l y c y l i n d r i c a l , has a separate c y l i n d e r ( u s u a l l y h a l f the diameter o f the f i r s t ) i n the c e n t e r known a s a p a r t i t i o n . The second c r i t i c a l component i s t h e o r i f i c e p l a t e a t t h e base o f t h e c o a t i n g chamber. A n o z z l e i s p o s i t i o n e d i n the c e n t e r o f the p l a t e t o spray upwardly t h r o u g h t h e p a r t i t i o n . The o r i f i c e p l a t e i s c o n f i g u r e d such t h a t a i r f l o w i s d i r e c t e d a t a h i g h volume a n d v e l o c i t y t h r o u g h t h e p a r t i t i o n , pneumatically t r a n s p o r t i n g the product past t h e nozzle w h i c h s p r a y s c o n c u r r e n t l y i n t o t h e f l u i d i z i n g m a t e r i a l . The number of smaller p e r f o r a t i o n s i n the p l a t e outside the area o f the p a r t i t i o n depend on t h e d e n s i t y a n d s i z e o f the p a r t i c l e s t o be coated. T h e i r p r i m a r y f u n c t i o n i s t o enhance f l u i d i z a t i o n , k e e p i n g the p a r t i c l e s i n t h e down b e d i n n e a r w e i g h t l e s s s u s p e n s i o n . F i n a l l y , a r i n g o f l a r g e r holes a t the outer perimeter o f the p l a t e p r e v e n t s t h e o c c u r r e n c e o f a "dead space" w h i c h would r e s u l t i n a p o r t i o n o f t h e product remaining uncoated. T h i s " c y l i n d e r i n a c y l i n d e r " c o n c e p t i s seen i n l a b a n d p i l o t s c a l e machines up t o about 24" i n c o a t i n g chamber d i a m e t e r . F o r p r o d u c t i o n machines, m u l t i p l e s o r c l u s t e r s o f p a r t i t i o n s w h i c h a r e 9" i n d i a m e t e r a r e


FLAVOR ENCAPSULATION

160

FILTER HOUSING

EXPANSION CHAMBER


PARTICLE FLOW PATTERN PRODUCT CONTAINER

LOWER PLENUM

AIR INLET

Fig. 1. Diagram o f a F l u i d Bed Dryer. Techniques, Inc.)

(Courtesy Glatt A i r

TOP SPRAY FILTER HOUSING

EXPANSION CHAMBER PARTICLE FLOW PATTERN

SPRAY NOZZLE

PRODUCT CONTAINER

AIR INLET

LOWER PLENUM

Fig. 2. Diagram o f a F l u i d Bed Granulator. Techniques, Inc.)




JONES


Fig. 3.

Diagram o f a Top Spray Coater. Techniques, Inc.)

4.

161


Diagram of a Bottom Spray (Wurster) Coater. A i r Techniques, Inc.)

(Courtesy Glatt



162


used. F o r i n s t a n c e a 32" W u r s t e r c o n s i s t s o f t h r e e p a r t i t i o n s and n o z z l e s i n s i d e a 32" d i a m e t e r chamber, and a 46" W u r s t e r chamber u s e s seven p a r t i t i o n s and n o z z l e s . T h i s i s p r i m a r i l y due t o n o z z l e l i m i t a t i o n s and t h e t a c k y n a t u r e o f most c o a t i n g s u b s t a n c e s . F l u i d i z e d Bed R o t a r y P r o c e s s o r A r e l a t i v e l y new t y p e o f f l u i d bed p r o c e s s i n v o l v e s t h e use o f a r o t a t i n g d i s c i n a c y l i n d r i c a l p r o d u c t c o n t a i n e r ( f i g u r e 5 ) . O r i g i n a l l y c o n c e i v e d t o produce h i g h e r d e n s i t y g r a n u l a t i o n s t h a n t h e c o n v e n t i o n a l f l u i d i z e d bed w i t h o u t s a c r i f i c i n g the p o s i t i v e a t t r i b u t e s such as p a r t i c l e s i z e c o n t r o l and g r a n u l e s t r u c t u r e , t h e machine has e v o l v e d i n t o an e x c e l l e n t p e l l e t i z e r . The t h r e e f o r c e s a t work a r e c e n t r i f u g a l , from t h e r o t a t i o n o f the d i s c w h i c h i s g e n e r a l l y speed a d j u s t a b l e ; v e r t i c a l f l u i d i z a t i o n as t h e h i g h v e l o c i t y a i r s t r e a m r u s h e s t h r o u g h t h e narrow s l i t a t t h e p e r i p h e r y o f t h e d i s c ; and g r a v i t y w h i c h c a u s e s t h e p r o d u c t t o cascade downward toward t h e d i s c s u r f a c e . The p a t t e r n can b e s t be d e s c r i b e d as a s p i r a l l i n g h e l i x . A n o z z l e i s p o s i t i o n e d t o s p r a y l i q u i d s c o n c u r r e n t l y and t a n g e n t i a l l y i n t o t h e fluidizing particles. Process Techniques - Agglomeration There a r e p r i m a r i l y 3 methods by w h i c h powders can be i n c r e a s e d i n s i z e i n the f l u i d i z e d bed — a g g l o m e r a t i o n by r e c r y s t a l l i z a t i o n , f i l m f o r m i n g b i n d e r s , and l a y e r i n g . Agglomeration by R e c r y s t a l l i z a t i o n Generally, very h y d r o p h y l l i c f i n e powders, when p l a c e d i n t o w a t e r wet r a p i d l y on t h e s u r f a c e , b u t t e n d t o form a mucous around t h e b u l k o f t h e powder. To f u l l y d i s s o l v e , the clump must erode w h i c h may t a k e q u i t e a w h i l e . A g g l o m e r a t i o n by r e c r y s t a l l i z a t i o n i s a s o l u t i o n f o r m a t e r i a l s t h a t a r e s o l u b l e i n water. The raw m a t e r i a l s a r e p l a c e d i n the p r o d u c t c o n t a i n e r o f the c o n v e n t i o n a l t o p s p r a y g r a n u l a t o r , f l u i d i z e d , and s p r a y e d a t a c o n t r o l l e d r a t e and d r o p l e t s i z e w i t h w a t e r . The d r o p l e t s o f w a t e r c o n t a c t t h e s u r f a c e s o f t h e powders, p a r t i a l l y d i s s o l v i n g them. These w e t t e d powders i n t u r n c o n t a c t o t h e r o u t e r s u r f a c e s r e s u l t i n g i n the formation o f agglomerates t h a t are c h a r a c t e r i z e d by a v e r y h i g h amount o f i n t e r s t i t i a l v o i d space. D i s p e r s i b i l i t y i s d r a m a t i c a l l y improved u s i n g t h i s t e c h n i q u e because, a l t h o u g h o v e r a l l s u r f a c e a r e a i s reduced, t h e s t r u c t u r e o f the g r a n u l e ( f i g u r e 6) i s such t h a t w a t e r c o n t a c t i n g t h e s u r f a c e i s w i c k e d i n s i d e and d i s s o l v e s t h e agglomerate from w i t h i n . A disadvantage i s t h a t agglomerate s t r e n g t h i s r e l a t e d t o p o r o s i t y , hence t h e s e g r a n u l e s t e n d t o be more f r i a b l e t h a n m a t e r i a l s p r o d u c e d using f i l m forming b i n d e r s . A g g l o m e r a t i o n by F i l m Forming B i n d e r s When u s i n g m a t e r i a l s t h a t a r e i n s o l u b l e i n w a t e r , and a l s o where g r a n u l e s t r e n g t h i s an i s s u e , agglomerating u s i n g a f i l m forming or hardening binder i s recommended. G r a n u l e s i z e and s t r e n g t h a r e a f u n c t i o n o f t h e t y p e and c o n c e n t r a t i o n o f the b i n d e r and, i n g e n e r a l , t h e a g g l o m e r a t e s have a much lower i n t e r n a l p o r o s i t y ( f i g u r e 7) t h a n t h o s e p r o d u c e d by r e c r y s t a l l i z a t i o n . ( 2 - 6 , 7)



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163

ROTOR

Filter Housing

0

Expansion Chamber

Product Container Product Container i

. 5.

f

Lower Plenum

Diagram o f a Tangential

E x p a n d e d View A - Product Chamber

C - DUc Gap or Silt

Β - Variable Speed DUo

D - Spray Nozzle

pray Coater.

(Courtesy G l a t t A i r

Techniques, Inc.)


164



Fig. 6.

Scanning electron photomicrographs of spray d r i e d f l a v o r before and a f t e r agglomeration by r e c r y s t a l l i z a t i o n . A. Before processing. A - l . magnification - 125x; A-2. magnification = 800x; A-3. magnification - 1250x. B.

Agglomerate a f t e r processing. B - l . magnification = 6Ox, B-2. magnification = 250x.



JONES

. 7.


Scanning electron photomicrograph o f a granule created by f i l m forming binder method. Magnification = 100 x.


166



Agglomeration by Layering I n t h e l a y e r i n g t e c h n i q u e , a s s m a l l agglomerates a r e formed, p r i m a r y p a r t i c l e s become a t t a c h e d t o t h e n u c l e i i a n d s e v e r a l s m a l l agglomerates c o a l e s c e i n t o l a r g e r ones. The d i f f e r e n c e between t h e s e g r a n u l e s and t h o s e produced by o t h e r t e c h n i q u e s i s t h a t t h e r e i s v e r y l i t t l e i n t e r n a l p o r o s i t y . As a r e s u l t t h e y t e n d t o d i s s o l v e more s l o w l y , b u t have good s t r e n g t h and w i l l l i k e l y w i t h s t a n d f u r t h e r p r o c e s s i n g such a s c o a t i n g o r a v i g o r o u s b l e n d i n g o p e r a t i o n . The a b i l i t y t o produce agglomerates i n t h i s manner i s v e r y much dependent on t h e n a t u r e o f m a t e r i a l s b e i n g p r o c e s s e d . G e n e r a l l y t h e s e t y p e s o f p r o d u c t s a r e produced i n t h e r o t o r ( t a n g e n t i a l s p r a y ) system because o f i t s h i g h amount o f s h e a r and c i r c u l a r t u m b l i n g a c t i o n . Process Techniques -

Instantizing

A category o f processing r e f e r r e d t o as i n s t a n t i z i n g can use a combination o f r e c r y s t a l l i z a t i o n o r a hardening binder as d e s c r i b e d p r e v i o u s l y , b u t may a l s o make u s e o f t h e f l u i d i z e d bed's m i x i n g abilities. A s u r f a c t a n t c a n be u n i f o r m l y d i s t r i b u t e d i n a b e d o f powders and improve t h e d i s p e r s i b i l i t y w i t h o u t a l t e r i n g p a r t i c l e s i z e . A p o s s i b l e disadvantage o f t h i s technique i s t h a t s u r f a c t a n t s may i m p a r t some t a s t e t o t h e p r o d u c t . Process Techniques - Coating W i t h some changes i n p r o c e s s i n g c o n d i t i o n s a n d machine s t y l e s , c o a t i n g s c a n be a p p l i e d t o m a t e r i a l s r a n g i n g i n s i z e from a p p r o x i m a t e l y 100 m i c r o n s t o s e v e r a l m i l l i m e t e r s i n d i a m e t e r . C o a t i n g m a t e r i a l s a r e a v a i l a b l e which c a n p r o v i d e f o r s u s t a i n e d r e l e a s e o f t h e s u b s t r a t e , a c i d r e s i s t a n c e , o t h e r pH c o n t r o l l e d r e l e a s e , m o i s t u r e r e s i s t a n c e , temperature c o n t r o l l e d r e l e a s e , t a s t e and odor masking, a s w e l l a s a e s t h e t i c s . The d e s i r e d f i n i s h e d p r o d u c t c h a r a c t e r i s t i c s may r e q u i r e a c l o s e l o o k a t a l l t h r e e f l u i d i z e d bed methods, which a r e b y no means f u n c t i o n a l l y e q u i v a l e n t . B e f o r e d o i n g s o , however, a g e n e r a l r e v i e w o f f a c t o r s a f f e c t i n g p a r t i c l e c o a t i n g i s i n o r d e r . Of p r i m a r y c o n c e r n i s t h e s i z e o f p a r t i c l e t o be c o a t e d . T a b l e I i s a c h a r t p r o f i l i n g t h e Table I.

Comparison o f the Amount o f Coating Required t o Apply a Coating o f 0.01 mm onto P a r t i c l e s o f Various Sizes

UNCOATED PARTICLES PARTICLE SURFACE SIZE DIAMETER PARTICLES AREA/GRAM (US MESH) (mm) PER GRAM (mm ) 2

5 10 18 35 60 120 200 325

4.00 2.00 1.00 0.500 0.250 0.125 0.074 0.044

23 183 1,468 11,764 94,350 751,880 3,663,000 17,543,860

1,,157 2,,312 4,,610 9,,235 18,,490 36,,917 63,,004 107, ,018

COATED PARTICLES COATED COATING COATING DIAMETER ADDED I N PRODUCT (mm) (%) (%) 4.02 2.02 1.02 0.520 0.270 0.145 0.094 0.064

1.2 2.4 4.7 9.6 20.0 43.3 82.3 163.5

1.18 2.34 4.49 8.75 16.7 30.2 45.1 62.0



17.

JONES


167

amount o f c o a t i n g r e q u i r e d t o a p p l y a l a y e r 10 m i c r o n s t h i c k t o p a r t i c l e s o f v a r i o u s s i z e s . As can be seen, v e r y s m a l l p a r t i c l e s (150 m i c r o n s and s m a l l e r ) r e q u i r e s i g n i f i c a n t q u a n t i t i e s o f c o a t i n g t o p e r f o r m as d e s i r e d . As an example, a 325 mesh, o r 44 m i c r o n , p a r t i c l e would r e q u i r e 163.5 kg o f c o a t i n g m a t e r i a l ( s o l i d s ) t o be a p p l i e d f o r each 100 kg o f c o r e m a t e r i a l . A d d i t i o n a l l y , t h e c o a t i n g must be a p p l i e d i n some s o r t o f medium and a t some c o n c e n t r a t i o n i n l i q u i d . I f we assume a 10% s o l u t i o n c o n c e n t r a t i o n , 1,625 kg o f s o l u t i o n w i l l need t o s p r a y e d and t h e r e s u l t i n g p r o d u c t w i l l be o n l y 38.0% s u b s t r a t e ; t h e remainder, c o a t i n g m a t e r i a l . I n most circumstances, t h i s i s not very economical. A l s o , i t i s extremely d i f f i c u l t t o c o a t p a r t i c l e s t h a t s m a l l because o f equipment and formulation limitations. A n o t h e r c o n c e r n i s t h e v o l a t i l i t y o f t h e a p p l i c a t i o n medium. T a b l e I I shows t h e h e a t s o f v a p o r i z a t i o n o f commonly u s e d s o l v e n t s . Table I I .

Heats o f V a p o r i z a t i o n o f Commonly Used S o l v e n t s

SOLVENT

BOILING POINT (°o

Methylene C h l o r i d e Acetone Methanol Ethanol Isopropanol Water

40.0 56.2 65.0 78.5 82.4 100.0

DENSITY (g/cc) 1.327 0.7899 0.7914 0.7893 0.7855 1.000

HEAT OF VAPORIZATION (Kcal/ML) 0.118 0.172 0.232 0.266 0.213 0.542

The d i f f e r e n c e i n f i l m c o a t i n g q u a l i t y between t h e t h r e e f l u i d bed t e c h n i q u e s i s d r a m a t i c when u s i n g v o l a t i l e o r g a n i c s o l v e n t s as opposed t o w a t e r b a s e d systems. The e v a p o r a t i v e e f f i c i e n c y o f t h e f l u i d i z e d bed makes i t p o s s i b l e t o c o a t w a t e r s e n s i t i v e p r o d u c t s w i t h aqueous c o a t i n g m a t e r i a l s . C o a t i n g s can be a p p l i e d from w a t e r and o r g a n i c s o l v e n t based s o l u t i o n s , l a t e x o r p s e u d o - l a t e x m a t e r i a l s , and m a t e r i a l s w h i c h a r e s p r a y e d m o l t e n . F i l m s a p p l i e d from s o l u t i o n t e n d t o behave v e r y much a s h a r d e n i n g b i n d e r s and i t i s d i f f i c u l t to avoid agglomeration e s p e c i a l l y i n small p a r t i c l e c o a t i n g . T h i s tendency i s l e s s p r e v a l e n t when u s i n g t h e o t h e r t y p e s of coating materials.

General Process Variables R e g a r d l e s s o f whether t h e f l u i d bed p r o c e s s i s b e i n g u s e d f o r a g g l o m e r a t i o n o r c o a t i n g , s e v e r a l p r o c e s s v a r i a b l e s a r e common and a r e l i s t e d i n T a b l e I I I . The a p p l i c a b l e v a r i a b l e s f o r f l u i d bed g r a n u l a t i o n have been w e l l d e f i n e d ( 2 - 6 ) . The two most s i g n i f i c a n t c a t e g o r i e s a r e e v a p o r a t i o n r a t e and d r o p l e t s i z e . I n g e n e r a l , t h e h i g h e r t h e e v a p o r a t i o n r a t e , t h e more porous and weaker t h e a g g l o m e r a t e s w i l l be. However, s i n c e most p r o c e s s e s do n o t a d d r e s s t h e problem o f a p e r p e t u a l l y c h a n g i n g s p e c i f i c h u m i d i t y , i t i s advantageous t o o p e r a t e u s i n g a h i g h f l u i d i z i n g a i r t e m p e r a t u r e (and hence a h i g h e v a p o r a t i o n r a t e ) t o m i n i m i z e v a r i a t i o n s i n d r y i n g


168


c a p a c i t y due t o s e a s o n a l changes i n t h e weather. G r a n u l e s i z e i s d i r e c t l y p r o p o r t i o n a l t o d r o p l e t s i z e . This process almost Table I I I .

F l u i d Bed P r o c e s s i n g V a r i a b l e s

Evaporation Rate 1. F l u i d i z i n g a i r t e m p e r a t u r e 2. F l u i d i z i n g a i r volume 3. F l u i d i z i n g a i r s p e c i f i c

humidity


Droplet Size 1. S p r a y R a t e 2. A t o m i z i n g a i r p r e s s u r e / v o l u m e 3. S o l u t i o n c o n c e n t r a t i o n ( v i s c o s i t y e f f e c t s ) Nozzle Port S i z e P o s i t i o n o f Spray N o z z l e B a t c h S i z e (Mass e f f e c t s )

e x c l u s i v e l y uses b i n a r y n o z z l e s ; l i q u i d i s s u p p l i e d a t low p r e s s u r e and a t o m i z e d t o d r o p l e t s by a i r . The h i g h e r t h i s a t o m i z i n g a i r p r e s s u r e and volume, t h e s m a l l e r t h e d r o p l e t s w i l l be a t a g i v e n l i q u i d d e l i v e r y r a t e . Another f a c t o r a f f e c t i n g d r o p l e t s i z e i s v i s c o s i t y o f t h e s p r a y s o l u t i o n . As a r e s u l t i t i s i m p o r t a n t t h a t v i s c o s i t y remain c o n s t a n t d u r i n g p r o c e s s i n g ( k e e p i n g a h e a t e d b i n d e r s o l u t i o n c o v e r e d and a g i t a t e d , f o r example). N o z z l e p o r t s i z e i s s e l e c t e d t o accomodate s p r a y l i q u i d v i s c o s i t y and d e l i v e r y r a t e and may i n f l u e n c e d r o p l e t s i z e because i t a f f e c t s t h e v e l o c i t y o f l i q u i d a t a g i v e n s p r a y r a t e . A t low a t o m i z i n g a i r p r e s s u r e s and volumes, a low l i q u i d v e l o c i t y a l l o w s more c o m p l e t e a t o m i z a t i o n o f l i q u i d . U s i n g a s m a l l e r n o z z l e p o r t a t t h e same s p r a y r a t e g e n e r a l l y r e s u l t s i n a l a r g e r mean d r o p l e t s i z e due t o t h e h i g h e r l i q u i d d e l i v e r y v e l o c i t y . A t h i g h a t o m i z a t i o n a i r p r e s s u r e s and volumes, t h i s e f f e c t i s m i n i m i z e d . The p o s i t i o n o f t h e n o z z l e has an e f f e c t on t h e d i s t r i b u t i o n o f l i q u i d , a t e r m known as w e t t e d bed s u r f a c e a r e a . To a c h i e v e t h e most u n i f o r m g r a n u l a t i o n , t h e n o z z l e w o u l d be p l a c e d h i g h above t h e s t a t i c bed t o y i e l d t h e l a r g e s t w e t t e d bed s u r f a c e a r e a (see F i g u r e 2). I f a wide range o f p a r t i c l e s i z e s i s d e s i r e d , t h e n o z z l e c a n be p o s i t i o n e d low r e s u l t i n g i n l o c a l o v e r w e t t i n g p r o d u c i n g a q u a n t i t y of coarse granules. In s c a l e - u p from l a b o r a t o r y q u a n t i t i e s (up t o 10 kg) t o p r o d u c t i o n b a t c h e s (300 kg and u p ) , bed d e p t h i n c r e a s e s s i g n i f i c a n t l y . The most n o t a b l e consequence i s an i n c r e a s e i n f i n i s h e d p r o d u c t b u l k d e n s i t y , t y p i c a l l y i n t h e range o f 15% t o 20%. I n some i n s t a n c e s , t h i s i s a d i s a d v a n t a g e ( i f p r o d u c t i s packed by volume and a low d e n s i t y i s d e s i r e d ) . However, g r a n u l e s t r e n g t h i s u s u a l l y g r e a t e r as a r e s u l t o f t h e d e c r e a s e d i n t e r s t i t i a l v o i d space.



17.


JONES

169

When c o a t i n g , t h e same group o f p r o c e s s i n g v a r i a b l e s a p p l i e s . A h i g h f l u i d i z a t i o n a i r temperature may a d v e r s e l y a f f e c t f i l m p r o p e r t i e s and may p r e s e n t some r e a l c h a l l e n g e s w i t h t h e r m o p l a s t i c m a t e r i a l s . F l u i d i z a t i o n a i r volume i s g e n e r a l l y h e l d c o n s t a n t because i t s i g n i f i c a n t l y impacts t h e f l o w p a t t e r n o f t h e s u b s t r a t e which i s c r i t i c a l i n c o a t i n g o p e r a t i o n s . S p e c i f i c h u m i d i t y a f f e c t s t h e c o a t i n g p r o c e s s i n two ways. I f a low d r y b u l b temperature i s chosen t o accomodate a v o l a t i l e s o l v e n t , t h e h e a t c o n t e n t o f t h e a i r w i l l v a r y as s p e c i f i c h u m i d i t y v a r i e s . I n an aqueous c o a t i n g p r o c e s s , s p e c i f i c h u m i d i t y has an e f f e c t on d r y i n g c a p a c i t y s i m i l a r t o t h e f l u i d bed g r a n u l a t i o n p r o c e s s . D r o p l e t s i z e i s a g a i n a f f e c t e d by s p r a y r a t e , a t o m i z i n g a i r p r e s s u r e and volume, and l i q u i d v i s c o s i t y . In coating, droplets s h o u l d be s m a l l r e l a t i v e t o t h e p a r t i c l e s b e i n g c o a t e d t o a v o i d a g g l o m e r a t i o n . By comparison t o f l u i d bed g r a n u l a t i o n , s p r a y r a t e s a r e u s u a l l y s l o w e r , a t o m i z i n g a i r p r e s s u r e i s h i g h e r , and l i q u i d v i s c o s i t y i s lower. N o z z l e p o r t s i z e i s a l s o s e l e c t e d t o accomodate d e s i r e d s p r a y r a t e and v i s c o s i t y . The p o s i t i o n o f t h e n o z z l e i s v e r y significant. I n top spray c o a t i n g o p e r a t i o n s , the n o z z l e i s p o s i t i o n e d to spray l i q u i d counter c u r r e n t l y t o the flow of product (see F i g u r e 3 ) . I n t h e W u r s t e r system, t h e n o z z l e s p r a y s c o n c u r r e n t l y w i t h t h e w e l l o r g a n i z e d f l o w o f s u b s t r a t e (see F i g u r e 4 ) , and i n t h e r o t o r t e c h n i q u e , t h e n o z z l e s p r a y s c o n c u r r e n t l y i n t h e s p i r a l l i n g bed o f p r o d u c t (see F i g u r e 5 ) . The i n f l u e n c e o f b a t c h s i z e i n s c a l e - u p i s s i m i l a r t o g r a n u l a t i n g i n t h a t i t i s a mass e f f e c t . However, t h e c o r e m a t e r i a l i s g e n e r a l l y much more r e s i l i e n t and t h e problem, i f any, i s e r o s i o n from t h e s u r f a c e o f a f r i a b l e s u b s t r a t e . Top S p r a y C o a t i n g A p p l i c a t i o n s / C h a r a c t e r i s t i c s The t o p s p r a y system has been u s e d t o c o a t m a t e r i a l s as s m a l l as 100 m i c r o n s . S m a l l e r s u b s t r a t e s have been c o a t e d , b u t a g g l o m e r a t i o n i s almost u n a v o i d a b l e due t o n o z z l e l i m i t a t i o n s and t h e t a c k i n e s s o f most c o a t i n g s u b s t a n c e s . B a t c h s i z e s range from a few hundred grams t o a p p r o x i m a t e l y 1,500 kg. T y p i c a l l y , a s i n g l e n o z z l e wand w i t h up t o s i x l i q u i d d e l i v e r y p o r t s i s used, b u t m u l t i p l e n o z z l e systems have been a p p l i e d . F l u i d i z a t i o n i s a f f e c t e d by b a t c h s i z e . Thus, i t i s recommended t h a t t h e bowl volume be c o m p l e t e l y o c c u p i e d by t h e p r o d u c t upon c o m p l e t i o n o f t h e c o a t i n g p r o c e s s . B a t c h s i z e c a n be d e t e r m i n e d by the f o l l o w i n g equation: Β = V x D Β V D

where:

Batch s i z e o f the coated product i n kg. t o t a l p r o d u c t c o n t a i n e r volume i n l i t e r s . B u l k d e n s i t y o f t h e c o a t e d p r o d u c t i n g/cc.

A minimum o f 50% o f t h e p r o d u c t c o n t a i n e r volume s h o u l d be o c c u p i e d by t h e uncoated m a t e r i a l t o a l l o w an adequate f l u i d i z a t i o n p a t t e r n . Under t h e s e c o n d i t i o n s , a p p r o x i m a t e l y 100% c o a t i n g (based on s t a r t i n g w e i g h t ) can be a p p l i e d . Because o f t h e random f l u i d i z a t i o n pattern using t h i s process, coating f o r very p r e c i s e



170


r e l e a s e p r o p e r t i e s u s i n g water o r o r g a n i c s o l v e n t s i s d i s c o u r a g e d . However, t o p s p r a y i n g i s t h e system o f c h o i c e f o r c o a t i n g w i t h o u t any s o l v e n t (hot m e l t ) . The most s i g n i f i c a n t c h a r a c t e r i s t i c o f t h e t o p s p r a y method i s t h a t t h e n o z z l e s p r a y s c o u n t e r c u r r e n t l y o r down, i n t o t h e f l u i d i z i n g p a r t i c l e s . The f l u i d i z a t i o n p a t t e r n i s v e r y random and u n r e s t r i c t e d . As a r e s u l t , i t i s i m p o s s i b l e t o c o n t r o l t h e d i s t a n c e that the d r o p l e t s t r a v e l before c o n t a c t i n g the s u b s t r a t e . A p p l i e d f i l m s may c o n t a i n i m p e r f e c t i o n s such as p i n h o l e s and c r a t e r s ( 8 ) . The problem seems t o be most s e v e r e w i t h f i l m s a p p l i e d from s o l u t i o n s , e s p e c i a l l y from o r g a n i c s o l v e n t s . The p r o d u c t c o n t a i n e r o f t h e t o p s p r a y system i s d e s i g n e d such t h a t t h e r e a r e no r e s t r i c t i o n s t o p a r t i c l e f l o w , an i m p o r t a n t c o n s i d e r a t i o n when a t t e m p t i n g t o a p p l y a hot m e l t c o a t i n g . M a t e r i a l s w i t h a m e l t i n g p o i n t o f l e s s t h a n 100°C can be a p p l i e d t o t h e f l u i d i z e d p a r t i c l e s by c a r e f u l l y c o n t r o l l i n g t h e l i q u i d and a t o m i z i n g a i r t e m p e r a t u r e s , and t h e p r o d u c t bed temperature. The degree o f p r o t e c t i o n o f f e r e d by t h e c o a t i n g i s r e l a t e d t o t h e r a t e a t which i t i s a p p l i e d and c o n g e a l s . However, k e e p i n g t h e p r o d u c t temperature c l o s e t o the c o a t i n g ' s c o n g e a l i n g temperature r e s u l t s i n a s i g n i f i c a n t i n c r e a s e i n t h e v i s c o u s d r a g i n t h e bed. It i s for t h i s reason t h a t , f o r hot melt c o a t i n g , the unobstructed product c o n t a i n e r o f t h e t o p s p r a y system i s s u p e r i o r t o o t h e r f l u i d i z e d bed t e c h n i q u e s . F i g u r e 8 shows examples o f a p r o d u c t b e f o r e and a f t e r c o a t i n g u s i n g a molten m a t e r i a l . The advantages o f t h e t o p s p r a y system i n c l u d e t h e f a c t t h a t i t i s t h e l e a s t c o m p l i c a t e d o f t h e 3 machines, has t h e l a r g e s t b a t c h c a p a c i t y , and downtime between b a t c h e s can be o n l y m i n u t e s . I t s b i g g e s t d i s a d v a n t a g e i s t h a t i t s a p p l i c a t i o n s a r e somewhat l i m i t e d . Bottom Spray (Wurster) Coating Applic»tioiis/Characteristics The W u r s t e r bottom s p r a y system has a l s o been u s e d s u c c e s s f u l l y t o c o a t p a r t i c l e s as s m a l l as 100 m i c r o n s . A t t e m p t i n g t o c o a t s m a l l e r p a r t i c l e s may r e s u l t i n t h e same d i f f i c u l t i e s as d i s c u s s e d i n t h e p r e v i o u s segment. B a t c h c a p a c i t i e s range from a few hundred grams t o a p p r o x i m a t e l y 600 kg. Because f l u i d i z a t i o n q u a l i t y i s a f f e c t e d by b a t c h s i z e , a t l e a s t 50% o f t h e volume o u t s i d e o f t h e p a r t i t i o n s h o u l d be o c c u p i e d by t h e uncoated p r o d u c t . F i n i s h e d product b a t c h s i z e ( f o r f i n e and i n t e r m e d i a t e p a r t i c l e s ) can be d e t e r m i n e d by the f o l l o w i n g e q u a t i o n : . Β Where: Β ri r η L D

2

[%n h 2

2

- 1/2ηπΓ2 ί1 D 1,000

= f i n i s h e d p r o d u c t b a t c h s i z e i n kg.

-

r a d i u s o f W u r s t e r chamber i n cm. r a d i u s o f p a r t i t i o n i n cm. number o f p a r t i t i o n s = p a r t i t i o n l e n g t h i n cm. - f i n i s h e d p r o d u c t b u l k d e n s i t y g./cc.

Minimum b a t c h s i z e b e f o r e c o a t i n g o f s m a l l p a r t i c l e s c a n be d e t e r m i n e d by m u l t i p l y i n g "B" by 0.4 ( o r a p p r o x i m a t e l y 40% o f f i n i s h e d p r o d u c t c a p a c i t y ) . The b a t c h c a p a c i t y f o r c o a t i n g o f



17.


JONES

F i g . 8.

171

Photomicrographs showing a molten coating applied by top spray method. A.

Before processing. A - l . magnification = 150x; A-2. magnification = 500x.

B.

A f t e r processing. B - l . magnification = llOx; B-2. magnification = 500x.


172



t a b l e t s i s approximately o f up t o 10% w/w.

90% o f ( π Γ ι L / l , 0 0 0 ) D f o r c o a t i n g s 2

I f t h e c o a t i n g and c o r e b u l k d e n s i t i e s a r e s i m i l a r , c o a t i n g s o f 100-150% (based on s t a r t i n g w e i g h t ) may be a p p l i e d . F l u i d i z a t i o n i s a l s o a f f e c t e d by t h e a i r d i s t r i b u t i o n p l a t e c o n f i g u r a t i o n and t h e p a r t i t i o n h e i g h t . The f i n e r t h e p a r t i c l e s t o be c o a t e d a r e , t h e l e s s w i l l be t h e open a r e a i n t h e downbed s e c t i o n o f t h e o r i f i c e p l a t e and t h e s m a l l e r t h e gap between t h e p a r t i t i o n and o r i f i c e plate. The W u r s t e r system has t h e w i d e s t a p p l i c a t i o n range u s i n g b o t h w a t e r and o r g a n i c s o l v e n t s ; o n l y c o a t i n g w i t h h o t m e l t s i s discouraged. O r g a n i z e d p a r t i c l e f l o w and t h e immersed n o z z l e , c o n c u r r e n t s p r a y system appear t o o f f e r s u p e r i o r f i l m f o r m i n g c a p a b i l i t i e s . An example o f a W u r s t e r f i l m c o a t i n g i s shown i n t h e s c a n n i n g e l e c t r o n p h o t o m i c r o g r a p h i n F i g u r e 9. The p r i m a r y d i s a d v a n t a g e s o f t h i s system a r e t h a t i t i s somewhat complex, i s t h e t a l l e s t o f t h e t h r e e t y p e s , and t h e n o z z l e s a r e i n a c c e s s i b l e d u r i n g the p r o c e s s i n g . T a n g e n t i a l Spray Coating

Applications/Characteristics

The r o t a r y , o r t a n g e n t i a l s p r a y system, a l s o an immersed n o z z l e , concurrent spray technique, appears t o o f f e r s i m i l a r f i l m c h a r a c t e r i s t i c s as t h e W u r s t e r system. The s c a n n i n g e l e c t r o n p h o t o m i c r o g r a p h s i n F i g u r e 10 compare t h e s u r f a c e v i e w s o f b o t h t y p e s o f f i l m c o a t i n g . The r o t a r y system has been u s e d s u c c e s s f u l l y t o c o a t p a r t i c l e s as s m a l l as 250 m i c r o n s u s i n g o r g a n i c s o l v e n t s and w a t e r b a s e d c o a t i n g s . The p r o c e s s i s more s u s c e p t i b l e t o a d h e s i o n o f p a r t i c l e s t o t h e upper w a l l o f t h e p r o d u c t c o n t a i n e r (see F i g u r e 5) due t o s t a t i c e l e c t r i c i t y , hence c o a t i n g o f s m a l l e r and l i g h t e r p a r t i c l e s i s d i f f i c u l t e s p e c i a l l y when u s i n g o r g a n i c s o l v e n t s . B a t c h c a p a c i t i e s range from a p p r o x i m a t e l y 1 kg. t o 500 kg. L a b o r a t o r y equipment (up t o 500 mm d i s c d i a m e t e r ) t y p i c a l l y u s e s a s i n g l e n o z z l e , and p i l o t t o p r o d u c t i o n s c a l e r o t o r s (up t o 2,000 mm d i s c d i a m e t e r ) use from 2 t o 6 n o z z l e s . F l u i d i z a t i o n i s n o t a f f e c t e d by b a t c h s i z e as s i g n i f i c a n t l y as i n t h e o t h e r p r o c e s s techniques. Working c a p a c i t y i s a p p r o x i m a t e l y 50% o f t o t a l bowl volume, and t h e minimum b a t c h s i z e i s t h a t w h i c h i s n e c e s s a r y t o c a u s e t h e n o z z l e t o be f u l l y immersed s u c h t h a t t h e c o a t i n g l i q u i d i s n o t s p r a y e d t h r o u g h t h e bed. T h i s volume i s t y p i c a l l y about 15-20% o f t h e w o r k i n g c a p a c i t y . I f t h e b u l k d e n s i t i e s o f t h e c o r e and c o a t i n g m a t e r i a l a r e s i m i l a r , c o a t i n g s o f 600-800% (based on s t a r t i n g w e i g h t ) may be a p p l i e d . The r o t a r y p r o c e s s e x c e l s i n p r o d u c i n g h i g h p o t e n c y p e l l e t s u s i n g t h r e e t e c h n i q u e s o f l a y e r i n g o n t o a seed m a t e r i a l : (a) s p r a y i n g a w a t e r o r s o l v e n t s o l u t i o n o f s u b s t r a t e and b i n d e r , (b) s p r a y i n g a water or s o l v e n t suspension o f s u b s t r a t e (with a d i s s o l v e d b i n d e r ) , o r (c) s p r a y i n g a w a t e r o r s o l v e n t b i n d e r s o l u t i o n and d o s i n g t h e s u b s t r a t e powder o n t o t h e damp s e e d m a t e r i a l . The c h o i c e o f t e c h n i q u e depends on s e v e r a l f a c t o r s i n c l u d i n g s o l u b i l i t y and s t a b i l i t y o f t h e s u b s t r a t e . A d d i t i o n a l l y , f o r s u s p e n s i o n l a y e r i n g and powder d o s i n g , i t i s a l m o s t mandatory t h a t t h e l a y e r e d powder be m i c r o n i z e d ( l e s s t h a n 10 m i c r o n s ) t o maximize y i e l d and p r o v i d e a smooth s u r f a c e f o r subsequent



17. JONES

F i g . 9.


173

A bottom s p r a y (Wurster) f i l m c o a t i n g , s u r f a c e a n d c r o s s - s e c t i o n a l views. (Reprinted with permission o f P h a r m a c e u t i c a l Technology, c o p y r i g h t 1985.) A. B.

S u r f a c e v i e w , m a g n i f i c a t i o n = lOOx. C r o s s s e c t i o n , m a g n i f i c a t i o n = lOOOx.

F i g . 10. P e l l e t s c o a t e d w i t h e t h y l c e l l u l o s e i n a n o r g a n i c s o l u t i o n . (Reprinted w i t h p e r m i s s i o n o f Pharmaceutical Technology, c o p y r i g h t 1985.) A. B.

W u r s t e r c o a t i n g , s u r f a c e v i e w , m a g n i f i c a t i o n = 100 x. R o t o r c o a t i n g , s u r f a c e v i e w , m a g n i f i c a t i o n = 100 x.



174


F i g . 11. S c a n n i n g e l e c t r o n p h o t o m i c r o g r a p h showing p r o d u c t l a y e r e d byt a n g e n t i a l s p r a y method. M a g n i f i c a t i o n = 175 x.



17.

JONES


175

overcoating. The r e s u l t i n g p e l l e t s w i l l be very uniform i n p a r t i c l e s i z e d i s t r i b u t i o n because of the narrow s i z e d i s t r i b u t i o n of the s t a r t i n g seed material, t y p i c a l l y a non-pareil sugar seed, or regular shaped c r y s t a l . Figure 11 shows a cross section of a drug layered p e l l e t . The process variables which are unique to the rotor system primarily involve the d i s c s l i t width, the d i s c configuration and r o t a t i o n a l speed. The rotary system was conceived as a higher intensity granulator than the conventional f l u i d i z e d bed. The d i s c surface, which may be configured with a v a r i e t y of surfaces from simple a n t i - s l i d e b a f f l e s to a multi-pyramid type waffle plate, and high rotational speed impart an increased mechanical force on the substrate. Hie v e l o c i t y o f the f l u i d i z a t i o n a i r through the peripheral s l i t controls the rate a t which the bed tumbles or s p i r a l s . For layering or coating, the d i s c should be smooth and a r o t a t i o n a l speed selected (less than one-half o f the speed used when granulating) such that p a r t i c l e motion i s rapid, but uniform. There i s a large v e l o c i t y gradient from the d i s c surface through the p a r t i c l e bed and any type of b a f f l e may cause fracture of the p e l l e t s , e s p e c i a l l y as the layer becomes thicker. The rotary tangential spraying system has a r e l a t i v e l y wide a p p l i c a t i o n range, i s the shortest machine i n height of the three, and allows nozzle access during processing. I t has the a b i l i t y to prodtjoe high potency p e l l e t s as well as to allow subsequent overcoating (for a l l types of release)., I t s primary disadvantage i s that i t exerts the greatest mechancial stress of the three methods and, thus, i s discouraged f o r use with f r i a b l e substrates. Summary Although there are l i m i t a t i o n s i n capacity, the batch f l u i d i z e d bed system has enjoyed popularity i n the pharmaceutical industry and with s p e c i a l t y products f o r the food and chemical industries. I t s a b i l i t i e s i n mixing and heat and mass transfer make i t very e f f e c t i v e for processing a v a r i e t y o f products. The three f l u i d i z e d bed techniques have some common features and process variables, but each has unique advantages and l i m i t a t i o n s . C r i t e r i a such as economics, product and process variables, and desired product performance a f f e c t the s e l e c t i o n of the process from the laboratory scale to commercialization.

References 1.

Wurster, D.E., U.S. Patent 2,648,609 (1953).

2.

Schaefer, T. and O. Worts, "Control of Fluidized Bed Granulation, I. Effects of Spray Angle, Nozzle Height and Starting Materials on Granule Size and Size Distribution," Arch. Pharm. Chemi. Sci., Ed. 5, 1977, pp.51-60.

3.

Schaefer, T. and O. Worts, "Control of Fluidized Bed Granulation, II. Estimation of droplet Size of Atomized Binder Solutions," Arch. Pharm. Chemi. Sci., Ed. 5, 1977, pp. 178-193.



176


4.

Schaefer, T. and O. Worts, "Control of Fluidized Bed Granulation, I I I . Effects of Inlet A i r Temperature and Liquid Flow Rate on Granule size and Size Distribution. Control of Moisture Content of Granules in the Drying Phase," Arch. Pharm. Chemi. Sci., Ed. 6, 1978, pp. 1-13.

5.

Schaefer, T. Granulation, Granule Size Ed. 6, 1978,

6.

Schaefer, T. and O. Worts, "Control of Fluidized Bed Granulation, V. Factors Affecting Granule Growth," Arch. Pharm. Chemi. Sci., Ed. 6, 1978, pp. 69-82.

7.

Davies, W. L. and W. T. Gloor, J r . , "Batch Production of Pharmaceutical Granulations in a Fluidized Bed," J. Pharm. Vol. 60 No. 12, December, 1971.

8.

and IV. and pp.

O. Worts, "Control of Fluidized Bed Effects of Binder Solution and Atomization on Size Distribution," Arch. Pharm. Chemi. Sci., 14-25.

Mehta, A.M. and D.M. Jones, "Coated Pellets under the Microscope," Pharm. Tech., 9(6), 1985, pp. 52-60.

RECEIVED

March 8,

1988


Sci.,

Controlling Particle Size and Release Properties - American Chemical

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