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SPRAY DRYINGFORMULATION OF SOLIDS WITH ADJUST.PART. PROPERTIES

SPRAY DRYING

Formulation of solids with adjustable particulate properties

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Pharm / Bio-Engng. Pharm / Bio-Engng. Pharm / Bio-Engng. Pharm / Bio-Engng. Lecture and Practical CourseLecture and Practical CourseLecture and Practical CourseLecture and Practical Course

March 2013

TITLE OF LECTURE

P. Walzel, Febr, 2013

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Bio- und Chemieingenieurwesen Mechanische - VT , MV MV MV MV

Influence of spray process on product APV SeminarAPV SeminarAPV SeminarAPV Seminar

TYPICAL SPRAY DRYING PROCESS

P. Walzel, April,5th, 2012

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March 2013 P. Walzel, Febr, 2013

Influence of spray parameters and

FEATURES OF SPRAY DRYING

- Liquid feed is dispersed into droplets within hot air

- Evaporation holds the particle temperature low (40 to 50°C)

- Particles must have large distances as long as sticky

- Residence time lies within seconds

- Low temperature afterdrying step possible in dense packing

CHARACTRISTICS OF SPRAY DRYING (3)


APV SeminarAPV SeminarAPV SeminarAPV Seminar






ϑin = constϕ = const

X

X∞ f ϕ ,ϑ( )C RP

non hygroscopic

hygroscopic

t timea) course of water content

c) drying rate vs. water contentX water content

dXdt

dXdt

t time

hygroscopic

C RP

mesoporous

micro porous

b) course of drying rate

C RPC RP

hygroscopic

drying process

d) drop diameter vs. timet time

dd0

2

droplets in settling state(e.g. levitator, falling tower)

solidificationof surface

1

0

0,5

1−ε( ) ≈ 0.6

DRYING OF DROPLETS/PARTICLES AT A CONSTANT GAS STATE (4)








The drying time for pure solvent droplets as water can be estimated from a heat balance

transferred energy by convection is equal to evaporation energy for Reg = 0 => Sh=Nu=2 => α = 2λg/2r

α AΔϑm = m·Δhev, 4πr λgΔϑm = V·l ρl Δhev

as α = λg/r : ∂V/∂t = 4πr2(∂r/∂t), λgΔϑm/ ( ρlΔhev) ,

tev = D02ρlΔhev /(8 λgΔϑm)

∂r

r

example

particle diameter D0 = 100µmheat of evaporation Δhev = 2330 kJ/kglog temp. difference: Δϑm = 70 Kheat cond. of gas: λg = 0.029 W/mKdensity of fluid: 980 kg/m3

tev = 1.38 s

Q·

V· =∂V/∂t =4r2π(∂r/∂t)

Δϑm = ϑ 00 - ϑwb

€

rdrR

r=0

∫ =λgΔϑm

ρlΔhevdt

t=0

tev

∫

ϑwb

ϑ 00

DRYING TIME (5)








conditions at state 3' can be obtained from aheat balance. In practice ϑwb lies below the ac-tual surface temperature of moist particleswithin CRP but can be used as an estimated

productresid moist. 0.1 < x < 10 %

frequently larger than desired

mist isotherm

constant enthalpy

Δϑm =[(ϑ2−ϑwb)-(ϑ3'−ϑwb)] / ln[(ϑ2−ϑwb)/(ϑ3'−ϑwb)]

DRYING OF MOVING DROPLETS/PARTICLES (6)








I. concurrent II. counter current

Δϑm =ϑg2 −ϑ f( )− ϑg3 −ϑ p( )

ln ϑg2 −ϑ f( ) ϑg3 −ϑ p( )⎡⎣ ⎤⎦Δϑm =

ϑg2 −ϑ p( )− ϑg3 −ϑ f( )ln ϑg2 −ϑ p( ) ϑg3 −ϑ f( )⎡⎣ ⎤⎦

consequence:• thermal stress on particle stronger in case II

• higher effciency of case II

• case II only possible for coarse material

constraitns in case II:• low temperature sensitivity • large particles:

a) falling towerb) fountain arrangement

FLOW CONDITIONS IN SPRAY DRIERS (7)







Fakultät Bio- und Chemieingenieurwesen Lehrstuhl Mechanische Verfahrenstechnik

Prof. Dr. techn. Walzel (15.01.13)

Produktdesign

7 Sprühtrocknung

16

Limitierende Faktoren bei der Sprühtrocknung, Verdampfungszeit

Der erste Trocknungsabschnitt kann ermittelt werden, da die Oberflächentemperatur des Partikels im Bereich von ϑwb

liegt. Der folgende Trocknungsabschnitt treibt die Wasserfront, die durch die mit Wasser gefüllten Poren innerhalb der Partikel gebildet wird, zurück. Um ihn zu bestimmen sind experimentelle Untersuchungen nötig. Da die Trocknungsrate selbst von der Struktur und Anordnung der Partikel abhängt, liegt ein gekoppeltes System vor, dass z.T. nur teilweise theoretisch beschreibbar. Zur Einschätzung der Trocknungszeit im ersten Trocknungsabschnitt sind in Tabelle 1 die Verdampfungszeiten für Tropfen reinen Wassers gegeben. Tab.1: Verdampfungszeit von Tropfen an der Luft, ϑG = 200°C, ϑwb 47°C

Durchmesser d [μm] 10 50 100 200 500 1000

Verdampfungszeit τ[s] 0,006 0,15 0,61 2,5 15 61

Beim Gegenstrom wird ein wird eine minimale Sinkgeschwindigkeit benötigt um einen Gasstrom in entgegengesetzte Richtung zu ermöglichen. In Tab. 2 sind einige Sinkgeschwindigkeiten gegeben. Tab. 2: Sinkgeschwindigkeiten von Tropfen an der Luft ρp = 1000kg/m³

Durchmesser d [μm] 10 50 100 200 500 1000

Sinkgeschwindigkeit [s] 0,002 0,06 0,21 0,67 2,2 4,1 In Tabelle 3 sind die Daten der theoretischen Eindringtiefen in Luft gegeben, wenn die Partikel horizontal eingespritzt werden. Partikel in einem kontinuierlichem Strahl haben höhere Eindringtiefen, weil sie von der Luft mitgerissen werden. Tab. 3: Eindringtiefe von Tropfen in Luft v0 = 40m/s

Durchmesser d [μm] 10 50 100 200 500 1000

Eindringtiefe l [m] 0,01 0,253 1,01 3,5 12 40



Produktdesign

7 Sprühtrocknung

17

Einfluss des Tropfendurchmessers auf Betriebsbedingungen

Max. Tropfengröße d [μm]

• Tro

cknu

ngsz

eit [

s]

• Sin

kges

chw

indi

gkei

t [m

/s]

• Ver

wei

lzei

t [s]

• Trocknungszeit:

• Sinkgeschwindigkeit:

• Verweilzeit:

• Verzögerungsstrecke:

2dvd s

2~ d

dd

112

2xLx B



Produktdesign

7 Sprühtrocknung

9

Adsorptionsisotherme / Magnetschwebewaage

Quelle: Gnielinski, Mersmann Thurner: "Verdampfung, Kristallisation, Trocknung", Vieweg 1993

Abb.1: Gleichgewichtsfeuchte in Kartoffelchips in Abhängigkeit von Temperatur und relativer Luftfeuchtigkeit



Abhängigkeit der Glasübergangstemperatur Tg von der Produktfeuchte

Produktdesign

7 Sprühtrocknung / Trocknung

13

E. Tsotsas und A. Mujumdar: „Modern Drying Technology“, 2011, Wiley-VCH

simple swirlpressure nozzle

pneumatic ortwo fluid nozzle

rotating wheels - holes - vanes

SPAYING METHODS AND DROP SIZE (10)


drop size: 0.05 to 0.5·D 50 < dv.50 < 500 µm

nozzle diameter: 0.5 mm < D < 4 mm

pressure: 20 < Δp < 200 bar

PSD: narrow, 1.4 < SP < 1.8spray angle: Θ = 40° - 60° thenturbulent free jet with 20°

drop size: 0.005 to 0.05·D 10 < dv.50 < 300 µm

nozzle diameter: 1 mm < D < 5 mm

pressure: 3 < Δpg < 10 bar

PSD: wide, 2 < SP < 3spray angle: Θ = 20° turbulent free jet with 20°

drop size: 30 < dv.50 < 200 µm

hole diameter: 5 mm < Dh < 20 mm

no pressure

PSD: 2.5 < SP < 3.5spray angle: Θ = 120°divergent spray




SPRAY DRIERS AND SPAYING METHOD (8)


nozzle towerswheel towers

agglomeration towertower




assuming no agglomerationthe particle size is stronglylinked to the initial drop size

porosity ε is frequently about0,5 to 0.6, particles are closeto drop diamters !

EXPECTED PARTICLE SIZES (9)


by a simple mass balance onecan estimate the particle sizecompared to the drop size

dp/d = [ϕs/(1-ε)]1/3

ε ... porosity of final particleϕs = Vs/(Vs+Vl) ... volumetricsolids content of slurry




SIMPLE PRESSURE NOZZLES (12)


·V ~ ΔΔΔΔp1/2·D2

d ~ Dn/Δ/Δ/Δ/Δpm

·V ~ ΔΔΔΔp1/2·D2

d ≈ 2D ·V ~ ΔΔΔΔp1/2·D2

d ~ D2/3/Δ/Δ/Δ/Δp1/3 ·V ~ ΔΔΔΔp1/2·D2

d ~ D0,6/Δ/Δ/Δ/Δp0,4

dmin ≈ D/20 dmin ≈ D/4dmin ≈ 2D

a) laminar jets b) sheet nozzles c) full cone nozzles




FSD ≈ sheetand swirl noz-zles

ZSD ≈ pneumticnozzles

VKD ≈ full conenozzles

sprinkler ≈ la-minar operatedcapillarries

LAMROT ≈ la-minar rotatingwheel sprayer

DROP SIZE DISTRIBUTION DATA (11)





TURBULENT BREAKUP (13)


sheet breakup

We = 42.000 D = 10 mm water

breakup pointmoves towardsnozzle with in-creasing pressure- ---> no more at-tenuation possible, influence of κ κ κ κceases

d32 = f (Tu, δδδδ0, Θ, Θ, Θ, Θ, Weδδδδ, , , , gas phase) .. ? sparse information in literature

SHEET WITH AERODYNAMICWAVES AND SUPERIMPOSEDSTOCHASTIC 2D- STRUCTURE

LZ

picture: E. Musemic

picture: D. Feggeler




"Product Quality" to a large extend depends on dried materials, however influence on structure and morphology due to drying condition, i. e. the drying course (no agglomertion !)

CRPd >>CRPd<

time

tem

pera

ture

gas or air

small particles

large particles

Systematicanalysis in detailis stilloustanding

assessment ofparticle sizefractions andtheir specificmorphologyquality resp. isrequired

t ~ d2

PRODUCT QUALITY / MORPHOLOGY (14)





Narrow PSD only at low pressures ΔΔΔΔp < 50 bar and with uniform spray patternnarrow PSD only at low pressures Dp < 50 bar and with uniform spray pattern

OBSERVATION OF SPRAY PATTERN / STRANDS (15)


Commercial nozzles differ in uniformity of the spray. Strands should be avoided

Observation recommended




narrow PSD only at low pressures Dp < 50 bar and with uniform spray pattern

PNEUMATIC NOZZLES DROP SIZE ESTIMATES (16)


External mixing nozzles, see e.g. D. Hede, et.al., Chem. Engng. Sci.63 (2008), 14, 3821-3842-

glycerol- water 100 mPas

water

P. Walzel, Chem.-Ing.-Tech. 62 (1990)12, 983-94:d32/D = C1[ΔΔΔΔpg*/(1+µ)2]m·(1+C2 Ohn) with Δpg*=ΔpD/σ, µ = ·ml /

·mg, Oh = η/(σρD)1/2

for Dp/D = 3,5 and Sp/D = 0,3 between: 1 < η < 100 mPas and 1 < Δp < 3 bar obtained with MALVERN LDS: C1 = 0,35; C2 = 2,5; m = - 0,4; n = 1

prefilmingsurface

turbulentfree jet turbulent free jet




industrial atomizers

ROTARY ATOMIZERS, FLOW CONDITIONS (17)





ROTARY ATOMIZERS, OPEN CHANNEL FLOW AND BREAKUP (18)


EFFECTS ON DROP SIZE • turbulent discharge • extension of threads • interaction with stagnant air




Laminar betriebener RotationszerstäuberNenndurchsatz 400 kg/h

LAMROT WHEEL


(19)





Particles from Large Spray Dryer, PT Lab (20)

Characterization of particles

• SP = (dV90-dV10)/dV50 = 0.75 !

• again smooth surfaces at A (90°C), like on small spray dryer with 60°C and 90°C

• again rough surfaces at B, like on small spray dryer with 130°C

• porosity and particle size inde- pendent on drying temperature

• no assessment regarding dosing and release behavior yet

cooperation with the group of Prof. N. A. Urbanetz

Helos/RodosSympatec

B A

Q3

/ %

Bio- und Chemieingenieurwesen Mechanische - VT MV MV MV MV




"Product Quality" to a large extend depending on dried materials, however influencing of structure and morphology within

limits is possible

Classification of typical materials:a) Crystallizing and crust forming materials as e.g. dissolved low molecular solids,

b) Skin forming solutions of high molecular solids as polymers,

c) Suspensions with small solid primary particles d < 2µm,

d) Suspensions containing large primary particles d > 5µm

e) Complex mixtures and emulsions.






Compact particles

Core shell structures

shrunk structures

TRENDS IN PARTICLE MORPHOLOGY (22)


• large primary particle • high solids content • low drying velocity • large slurry droplets • stabilized suspensionstabilizationstastatus

• dissolved polymers• amorphous preciptiation

• small primary particles• low concentrations• high drying velocity• crystallization of dissolved components




Drying of skinforming materials

Walton, D. E. , C. J. Mum-ford (1999b) The morpho-logy of spray-dried particles:The effect of process varia-bles upon the morphologyof spray dried particles.Chem.-Engng. Researchand Design, 77 (5): 442-490.

MORPHOLOGY OF SKIN FORMING MATERIALS (23)





100 µm

100 µm

TYPICAL POLYMER PARTICLES, SBS LATEX (24)


Polystyrene-Polybutadien particles spray dried from 35% b. wt solution

• smooth particles • indented structure

Drying condition • ϑϑϑϑa = 120°C





TYPICAL AMORPHOUS PARTICLES, LACTOSE (25)


LACTOSE PARTICLES • transparent • amorphous structure

DRYING CONDITIONS • xs = 20% wt • ϑϑϑϑa = 90°C




TYPICAL CRYTALLINE PARTICLES, NACL (26)


NaCl particles spray dried from 20% b. wt solution

crystal shaped product






CUT THROUGH NACL-PARTICLES EMBEDDED IN RESIN (27)


NaCl particles spray dried from 20% b. wt solution

• crystal shaped product • void core






100 µm

Typical Particles, Ceramics: Si3N4 (28)


Spray dried product from ceramic primary particles d = 0.8 µm with different status of stabilization

• highly stabilized (large or very low pH) -> dense shell with ex- tended void in the center • low stabilization -> low but uniform density

according to M. Fries, Diss. TU Freiberg, Germany, 2008: "Produktgestaltung kera-mischer Sprühgranulatefür die uniaxiale Pressver-dichtung zu grossformi-gen Bauteilen"




300µm 50µm 300µm 50µm

TYPICAL PARTICLES, CERAMICS: BASO4 (29)


Spray dried product from ceramic primary particles d = 4 µm at 60°C slurry feed temperature left - and with 160°C slurry temperature right

• normal spray condition gives "doughnuts" • flash condition leads to fairly dense particle

according to K. Monse,Diss. "Zur Strukturbildungvon sprühgetrocknetenPartikeln", TU Dortmund,2009




200 µ

AGGLOMERATE AND FREEZE DRIED PARTICLE (30)


100 µm

structure formed by subli- mating of water from a 2 - mm mannite solution droplet frozen in liquid N2

full milk particle from inte- grated fluidized bed (FSD)

by courtesy of GEA NIRO




Materials, drying conditions and PSD influence the particle morphology and their physical properties

=> spraying method and conditions influences d50.3 and PSD

=> more information on quality and morphology in MDT, Vol. 3, Chapter 6, Walzel/Furuta

=> wide range in shaping and efficiation of particles by composition and process conditions






Spay Drying of D-Mannitol at Different Initial Drop Sizes, Dipl. Arb. Pauss (32)





OVERVIEW OF PARTICLE MAKEUP PROCESS OF INHALATES (33)

active carrier

SPRAY DRYER

MIXER

variance of doses PSD by LDS

particle morphology

active fines contentin aerosolaerosol<<<<<<<<<<

INHALER/IMPACTOR

JETMILL

active

d < 5 µm 10 < d < 60 µm

salbutamolsulfate (asthma therapy)

mannitol sol.15 %

1% active fines

Helos/RodosSympatec

Novolizer®,Viatris/ NGI Copley, Sci./HPLC

Hosokawa Alpine, 50AS Niro // TU Dortm.

Novolizer®,Viatris

Turbula T2C, Bachofen,CH

SEM,

weightbalance

Cooperation:Prof. N. Urbanetz

Bio- und Chemieingenieurwesen Mechanische - VT MV MV MV MV




=> primary task of SD is to provide solid particles from liquid feeds

=> fast solube materials can be obtained by very fast solidification (amorphous state) in presence of Polymers as PVA, PVP

=> SD experiments e.g. for Paracetamol formulation suitable for tabletting was sucessful

=> special powders as e.g. PULMOSOL (insuline) can be achieved by SD in combination with emulsification technology

=> even proteins (enzymes) or bacteria can be stabilized by proper excipients, e.g. trehalose as with differnt carbohydrates. Temperature is low and residence time is short (few seconds)

THANK YOU FOR YOUR ATTENTION !

PRODUCT PROPERTIES AND PROTECTIVE TREATMENT (34)





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