Coating Knowledge v4u4q

SEPISCHOOL TRAINING Acquire Coating Knowledge & Expertise

SEPPIC, an of

INTRODUCTION

INTRODUCTION Definition of coating To cover a surface permanently or temporarily using a suitable material • Coating:

generic term

• Film coating:

coating with a thin film

Film coating of solid dosage forms = common place in the pharmaceutical / functional food industries

INTRODUCTION Why film coat? To protect the tablet from its environment (air, light) Active ingredient unstable in light or in the presence of humidity Hygroscopic formulation Oxidizable active ingredient (atmospheric oxygen)

VALERIAN TABLETS

INTRODUCTION

To mask taste/odour/colour

To facilitate tablet ingestion

To facilitate packing (blister)

INTRODUCTION To colour Tablet identification Marketing purpose

Crestor 10mg (AstraZeneca)

Crestor 5mg (AstraZeneca)

INTRODUCTION …To colour Influence on the psychological component of treatment compliance: Pr Max Luscher capsugel study.ppt

To modify bioavailability (controlled release, entericcoated)

INTRODUCTION Training objectives Tablet film-coating Aqueous medium Immediate release

Not specifically discussed today: Film coating in organic solvent, enteric film coating, sugar coating, particle coating…

SEPISCHOOL Coating Theoretical training ( day 1)  Practical training in the laboratory ( day 2)

CONTENT I. The core II. Coating dispersion III. Equipment IV. Operating conditions V. Film coating steps VI. Problems encountered

I.

THE CORE

CORE Substrate variability • • • • •

Tablets Spheroids (micro-granules) Crystals Powders Capsules

Substrate physical properties • • • • • •

Size, density Geometrical shapes and dimensions Surface finish Porosity Friability Hardness and Weight

CORE Tablets

normal convex

Oval

Capsule Flat

CORE Tablets Good shape: • • • •

ROUNDED FORM MEDIUM CROSS-SECTION PRONOUNCED CURVATURE DIAMETER NOT TOO LARGE

Twinning

NO FLAT TABLETS

Erosion of sharp angles

Why? Bad mixing in the coating pan

CORE Tablets Resistance to crushing: • No major problem

Force to disrupt tablets > 70 N

CORE Tablets Friability

:

(very important factor)

• No friable tablets • In particular at the edges Friability < 0.5%

CORE Tablets Sensitivity to rotation :

No capping during the hardness and friability measurements

CORE Tablets Sensitivity to moisture: • Active ingredients • Excipients (disintegrants) • Drop test

CORE Drop Test - non hygroscopic tablet

T=0

T=20s

CORE Drop Test - hygroscopic tablet

T=0

T=10s

T=20s

II.

COATING DISPERSION

COATING DISPERSIONS Conventional composition: BINDER / FILLER

HYPROMELLOSE STARCH

(MCC)

(Film forming polymer)

SEPIFILM ™ SEPISPERSE™ DRY SEPICOAT™

DYES PLASTICIZERS

PIGMENTS LAKES

COATING DISPERSIONS FILM FORMING AGENT

COATING DISPERSIONS HYPROMELLOSE

Where R is H, CH3, or [CH3CH(OH)CH2]. Several grades: - Substitution type:

% OCH3 - % OCH2CH(OH)CH3 2208/ 2910

- Molecular weight

COATING DISPERSIONS PROPERTIES OF HYPROMELLOSE  Soluble in cold water  Insoluble in hot water The precipitation temperature varies between 50-90°C according the grades

 Available in wide range of viscosities according their molecular weight: from 3 to 100 000 s at 2% in water

 Derived from natural products (pulp)  Film forming properties  No toxicity or ecotoxicity

COATING DISPERSIONS Shin-Etsu Chemical Co., Ltd.

PHARMACOAT 603

Substitution type Viscosity (2% in water at 20°C)

606

615

Hypromellose 2910 ~3.6

~7.2

~18.0

COATING DISPERSIONS Shin-Etsu Chemical Co., Ltd.

500

COATING DISPERSIONS Assessment of mechanical properties of hypromellose films OUR TARGET •A hard film •A non brittle film So…. High values for tensile

•

Elongation at break

•

Tensile strength

strength and elongation

•

Elastic modulus

at break

COATING DISPERSIONS Shin-Etsu Chemical Co., Ltd.

ELONGATION AT BREAK OF HYPROMELLOSE FILMS Elongation at break (%)

30 25

Free films of polymers Free films of polymers + TiO2

20 15 10 5 0

P 603

P 606

P 603 + 20% P 606 + 20% TiO2 TiO2

COATING DISPERSIONS PLASTICIZERS LOW MOLECULAR WEIGHT ORGANIC MOLECULES, CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER

–

Cohesion forces

• Reduction of chain-chain interactions • Increased mobility of macromolecular chains

Polymer

Plasticizer

COATING DISPERSIONS LOW MOLECULAR WEIGHT ORGANIC MOLECULES, CAPABLE OF MODIFYING THE PHYSICAL PROPERTIES OF A POLYMER

Physical consequences: –  Film plasticity • Better mechanical properties – Resistance to deformation – Flexible, elastic films (high modulus of elasticity) – Continuous film

COATING DISPERSIONS PLASTICIZER assessment Influence of a plasticizer on the glass transition temperature (Tg) of polymers

Rigid glassy state

Mobile rubbery state

Tg

Temperature (°C)

COATING DISPERSIONS Influence of DBS (Dibutyl Sebacate) concentration in a dispersion of ETHYL CELLULOSE on the glass transition temperature (Tg) 150 130 110 Tg (°C) 90 70 Usual

50

temperature of the tablet bed

30 0

5

10

20

30

40

DBS concentration (%)

COATING DISPERSIONS Common plasticizers HYDROPHILIC

HYDROPHOBIC

PROPYLENE GLYCOL

TRIACETIN

GLYCERIN

ACETYL MONOGLYCERIDES

MACROGOL (PEG)

PHTHALIC ESTERS

MACROGOL 8 STEARATE

CASTOIR OILS

MACROGOL 40 STEARATE

DBS (DiButyl Sebacate) TRIETHYL CITRATE STEARIC ACID

COATING DISPERSIONS PIGMENTS - DYES o DYES: Water-soluble • Organic dyes which might migrate from the surface to the core. Risk of non-uniform colour. Bright colours. Mostly sensitive to light. o LAKES: Insoluble • Soluble dyes adsorbed on a solid substrate (aluminium lake). No migration. • Good covering power combined with TiO2 o PIGMENTS: Insoluble • TiO2 • Iron oxide (red, yellow, black) • Good covering power

COATING DISPERSIONS FILLERS Increase the dry matter concentration of the dispersion (without modifying the viscosity) : •To shorten the processing time •To reduce the cost of the formula

Typical concentration: 5-20 %

COATING DISPERSIONS FILLERS Examples: Lactose, MCC, pre-gelatinized starch, talc(1) – MCC improves film adhesion to the tablet :

Without MCC

(1) Talc is also used as an anti-tack agent.

With MCC

COATING DISPERSIONS OTHER INGREDIENTS SOMETIMES USED

• • • • • • •

Foam inhibitors (silicones) Brightening agents Sweeteners Surfactants Water repellent agents (stearic acid) Opacifiers (talc, silicates) …

III.

EQUIPMENT

EQUIPMENT A MODERN COATING EQUIPMENT

Inlet Air handling unit

Outlet air filter unit

(air heating system…)

Solution tank

Coating pan

EQUIPMENT • Pans • Perforated The most widely-used technology. • Solid Performance lower than that of perforated pans. Traditionally used for manual sugar coating (ladle).

• Fluid bed • Mainly laboratory apparatus. More rarely at industrial level. • Useful for rapid applications when screening coatings, for example. • Used for coating pellets and micro-granules.

EQUIPMENT • Solid pans

(conventional)

• Advantages: Simple design, inexpensive, easy to clean, adaptable (sugar coating, film coating, etc.) • Major drawback: Relatively ineffective drying by pulsed hot air at the substrate surface. Extensive dust formation if extraction system not appropriate.

EQUIPMENT • Solid pans with « Suction Paddles » immersed in the cores

EQUIPMENT • Perforated pan Hot air

A

B

•

Drying by pulsed hot air at the surface

•

Penetration of hot air into the tablet bed (A)

•

Extraction of the moisture by suction (B)

EQUIPMENT • Perforated pan

http://www.vectorcorporation.com/products/hicoater_lab.asp

EQUIPMENT • Perforated pan

Manesty XL lab

GMPC (Glatt Multi-Pan Coater) Thai Coater FC 15’’

EQUIPMENT •

Vertical Centrifugal Coater

EQUIPMENT • Spray system: GUNS Principle • SPRAYING OF THE FILM COATING LIQUID THROUGH A NOZZLE. THE FINE DROPLETS FORMED (Atomization) ARE DEPOSITED ON THE SUBSTRATE TO BE COATED. Quality of a good system • PRODUCTION OF DROPLETS OF SMALL DIAMETERS • TRANSFORMS COATING SUSPENSIONS CONTAINING UP TO 25% DRY MATTER INTO FINE DROPLETS • EASILY ADJUSTABLE: FLOW RATE AND ANGLE

EQUIPMENT • AIR SPRAY gun

Circle

Ellipse

EQUIPMENT • AIR SPRAY gun

Atomizing air

• Atomizing Air:

Converts the suspension into a “mist” • Pattern air/ Fan air:

Pattern air flattens the spray cone The more air the flatter the cone ABC nozzle from Glatt

Pattern air

EQUIPMENT • Spray system: GUNS – AIR SPRAY  Low air pressures (0.5 – 5.0 bars)  Nozzle diameters: 0.8 – 2.0 mm  Easy adjustments

– AIR LESS

 LOW FLOW RATE + VERY FINE DROPLETS  AQUEOUS FILM COATING

 HIGH FLOW RATE + LARGE DROPLETS

 High working pressures  ORGANIC FILM COATING  Low nozzle diameters: 0.2 – 0.4 mm, leading to nozzle clogging (suspensions) DROPLET SIZE DEPENDS ON SEVERAL FACTORS, INCLUDING VISCOSITY

EQUIPMENT • Nozzles – Bed to Gun distance: VERY IMPORTANT

• Too close: risk of wetting • Too far: risk of drying the atomized dispersion ("spray drying")

– Nozzle direction • Either top third of bed • Or middle • Prohibited area: at base of bed (bottom third)

– Observed values: • Distance: 15 to 25 cm • Nozzle diameter: 0.8 to 1.8 mm • Pressure: 2 to 5 bars

EQUIPMENT • AIR SPRAY gun 200/ 180 kg tablets/ 3 guns

Re-check: 25 cm

-at the beginning of each batch -when pan load changes

EQUIPMENT • AIR SPRAY gun

100% 70%

EQUIPMENT • AIR SPRAY gun Be careful to: - Gun to gun distance

If the distance is too low: Overlapping spray cones

EQUIPMENT • AIR SPRAY gun Be careful to: - Gun to side of the pan distance

EQUIPMENT • Spray system: PUMPS – PERISTALTIC • Standard used in the pharmaceutical industry

Multi-head pump (12)

IV.

OPERATING CONDITIONS Application parameters are more or less important to get an equilibrium between spraying flow rate and solvent evaporation. The purpose of all of these conditions is eventually to coat tablets avoiding meanwhile their alteration.

OPERATING CONDITIONS • Influence of following parameters – DRYING • Inlet Air Temperature • Drying Air Volume • % RH of Drying Air • Pressure inside pan – SPRAYING • Flow Rate • Pressure – PAN ROTATION

FLOW RATE

PAN ROTATION

DRYING

OPERATING CONDITIONS

Flow rate

Operating conditions permitting to perform a non-stressing coating for the tablets, obtain a satisfying film coat and provide a robust and optimized process

Main parameters

Secondary parameters

OPERATING CONDITIONS • DRYING PARAMETERS – Main Parameters: 1. Inlet Air Temperature 2. Drying Air Volume Adjustment of these 2 parameters according to: – Sensitivity of cores and drug substance – Spraying flow rate – Pan loading – Tablet size – Exhausting capability…

• Small tablets pack closer together • It’s harder to pull the air flow through the batch

OPERATING CONDITIONS • DRYING PARAMETERS – Secondary parameters: 1. % RH of Drying Air It does mainly act on the quality of the drying air. 2. Positive and negative pressure Influence of the pan coating pressure on removing dust Adjustment of the pan coating pressure according to: – Inlet and Outlet Air flow rate – Exhausting capability

OPERATING CONDITIONS • SPRAYING – Main parameter: • Spraying Flow Rate Adjustment of the spraying flow rate once setting:

– Spraying pressure – Drying air temperature – Drying air volume

For reasons of economy, it is desirable to work at the maximum spray rate. But, Begin the coating with a low spray rate When the base coating is applied, you can increase the spray rate

OPERATING CONDITIONS • SPRAYING – Secondary parameters: • Spraying Air Pressure Adjustment of the spraying air pressure according to: – Atomisation finesse desired – Spraying Flow Rate expected When you increase the air pressure: -the droplet size decreases then stabilizes -the droplet velocity increases

Too low pressure: - formation of big droplets - risk of overwetting

Risk of spray drying?

OPERATING CONDITIONS • SPRAYING – Secondary parameters:

• Fan air Pressure

Increasing fan air pressure

OPERATING CONDITIONS • SPRAYING A paper pulled through the spray

OPERATING CONDITIONS • MIXING OF TABLETS – This parameter does mainly operate on: – Colour homogeneity – Film coating quality ( inter and intra tablet coating uniformity) – Factors influencing the mixing of tablets: – Pan loading – Pan speed rotation – Deflectors – Size and shape of the tablets

OPERATING CONDITIONS •

PAN SPEED ROTATION Rotation too fast

- Visual aspect of tablet bed - In most of cases, increasing the pan speed improve the mixing of tablets

Decrease rpm

PAY ATTENTION TO CORE EROSION and EDGE DAMAGE ( in particular with friable tablets)

OPERATING CONDITIONS • DEFLECTORS Manesty study on deflectors

Manesty ‘tubular’ baffle

Manesty ‘ploughshare’ baffle

Manesty ‘rabbit ear’ baffle

-Tablet bed movement and hence product mixing is influenced by baffle design -Tubular baffle are more efficient at mixing than ‘ploughshare’ baffle (less time to achieve batch colour uniformity)

OPERATING CONDITIONS  Inlet air  Temperature  Inlet air volume

SET VALUES

 Coating spray rate  Batch size…

Exhaust air temperature/ tablet bed temperature = function (inlet T°, spray rate, inlet air V…) Monitoring outlet air temperature helps us determine if any of the others factors have changed or shifted

OPERATING CONDITIONS

4g/min/kg tablet 1 gun => 40g/min per gun

3g/min/kg tablet 5 guns => 188g/min per gun

V.

FILM COATING STEPS

FILM COATING STEPS • Solids content % w/w

% solids –

msepifilm  mwater  msepifilm

Example: 

Recommended solids content of Sepifilm™ LP: 12%

– –



(= dry matter content)

SEPIFILM™ LP: WATER:

12 grams 88 grams 100 grams

Frequent mistake!

–

False example: 

Recommended solids content of Sepifilm® LP: 12%

– –

WATER: SEPIFILM® LP: (10.71%)

100 grams 12 grams 112 grams

msepifilm % solids = mwater

FILM COATING STEPS • Weight Gain (=weight increase, dry deposit) – For convenience, the quantity of coating deposited is quantified by the increase in tablet weight: Example: 3% weight gain Tablet: 500 mg Tablet + coating: 500 mg  1.03 = 515 mg

FILM COATING STEPS • Weight Gain

(WG):

Actual

– After coating, the weight gain actually applied to the cores is calculated as shown below in of weight – WG actual • Measurement of the weight of 20 cores before film coating • Measurement of the weight of 20 tablets after film coating

WGactual

m 20 coated tablets - m 20 cores  m 20 cores

The actual WG is not always applicable for the following reasons:

– –

Tablet abrasion. Tablet weight decrease due to water evaporation.

FILM COATING STEPS • Weight Gain (WG) : Theoretical

mcoating dispersion %solids WGtheoretical  mcores The pan yield can be taken into : it is usually higher at industrial scale (~ 95%) than in the laboratory (~ 80%)

FILM COATING STEPS • Weight Gain

Typical values 100 mg:

5%

400 mg:

3%

1000 mg:

2%

the specific area 

FILM COATING STEPS • Dispersion

FILM COATING STEPS • Dispersion

FILM COATING STEPS • Gun settings (position, flow rate) • Dust removal • Tablet bed temperature increase – Ttablet bed = 40-45 °C  rotate alternately in both directions

• Spraying shutdown

60 C

BE D T em p (C)

• Spraying – Ttablet bed will fall Evaporation is an endothermic state change.

50 C

40 C

30 C

20 C 0 min

20 min

40 min

60 min

Time [min]

• Cooling: pan rotation alternately in both directions

80 min

FILM COATING STEPS

BE D T em p (C)

60 C

50 C

40 C

Acceptable 30 C

Over-wetting

Warm-up 20 C 0 min

20 min

40 min

60 min

Time [min]

80 min

FILM COATING STEPS Driacoater® 500 Solid content

LP 014 / Dry at 12 %

Batch size

3 kg

Spraying rate

7-15 g/min

Inlet air temperature

55-60 °C

Outlet air temperature

42 °C

Atomizing Air / Pattern pressure

3 bars

Air Flow

270 m3/h

Spraying time

70 min. (3 % w.g.)

FILM COATING STEPS

VI.

COATING ISSUES

COATING ISSUES Most of the problems noticed on the tablets during the coating process (or once it is achieved) can be classified in several categories but the three main ones are: 1. Problems due to coating conditions and/or equipments:  Picking/ sticking  Rough film coating (orange peel)  Logo bridging  Coating pan getting dirt 2. Problems due to tablet characteristics and defects:  Torn or cracked films  Blow-out of tablets  Dust formation due to friability of tablets 3. Problems due to coating products

COATING ISSUES Problems due to coating conditions and/or equipments • PICKING/ STICKING: small holes pulled in film  general or local over-wetting

PICKING - STICKING

COATING ISSUES Problems due to operating conditions • PICKING/ STICKING: small holes pulled in film  general or local over-wetting

CAUSE

SOLUTIONS

-OVERWETTING

-REDUCE THE FLOW RATE -INCREASE THE INLET/ BED T°C -INCREASE THE PAN SPEED -INCREASE DRYING AIR VOLUME

-STICKY FORMULA

-USE SEPIFILM RANGE (NON STICKY)

-SPRAY NOZZLES TOO NEAR FROM THE TABLET BED

-REPOSITION OF THE GUNS

COATING ISSUES Problems due to operating conditions • ROUGH film not smooth similar in appearance to an orange peel ROUGHNESS

COATING ISSUES Problems due to operating conditions • Rough film not smooth similar in appearance to an orange peel

CAUSE

SOLUTIONS

- IMPROPER ATOMIZATION PRESSURE (too large droplets)

- INCREASE ATOMIZING AIR PRESSURE

- SPRAY NOZZLES WRONGLY POSITIONNED TOO FAR FROM THE BED OF TABLETS

- REPOSITION OF THE GUNS

- IMBALANCE BETWEEN SPRAYING FLOW RATE/ DRYING AIR TEMPERATURE AND VOLUME : ' SPRAY DRYING '

- DECREASE DRYING AIR TEMPERATURE AND / OR VOLUME. - INCREASE THE SPRAYING FLOW RATE

COATING ISSUES Problems due to operating conditions • LOGO BRIDGING: the coating fills in the logo on the tablets LOGO BRIDGING

COATING ISSUES Problems due to operating conditions • LOGO BRIDGING: the coating fills in the logo on the tablets CAUSE

SOLUTIONS

-FILM WITH LOW ELASTICITY

-MODIFY OR INCREASE THE LEVEL OF PLASTICIZER -DECREASE THE % OF FILLER IN THE COATING FORMULATION

-A POOR LOGO DESIGN

-USE A DIFFERENT LOGO DESIGN

-A HIGH LEVEL OF DRY DEPOSIT

-REDUCE DRY DEPOSIT

-SPRAY-DRIED COATING PRODUCT IN THE LOGO

-AVOID SPRAY DRYING

COATING ISSUES Problems due to operating conditions • Pan coating getting dirt – During the coating, the wall of the pans are coated. As a consequence, film coating particles (more or less important) come unstuck from the walls and adhere directly on the surface of tablets. Turbulences may create dust formation CAUSE

SOLUTIONS

- BAD POSITION OF THE GUNS INSIDE THE COATING PAN (TOO CLOSE TO THE WALL)

- MODIFY THE SPRAY GUNS POSITION

- NON OPTIMIZED TABLET LOADING

- MODIFY THE SPRAY GUNS POSITION (IF YOU CAN) - INCREASE THE PAN LOADING

COATING ISSUES Problems due to operating conditions + tablets defects • CORE EROSION: small holes in tablet surface (loss of material from tablet surface)

CORE EROSION

COATING ISSUES Problems due to operating conditions + tablets defects

• Core erosion CAUSE

SOLUTIONS

-TABLETS SENSITIVE TO EROSION

-USE MORE BINDER IN THE TABLET FORMULATION

-EXCESSIVE PAN SPEED

-DECREASE THE PAN SPEED

With core erosion, it is not possible to really quantify the film-coating agent dose sprayed on the tablets during the coating process. A high friability can be linked to a lack of binding power in the tablet formula or excessive lubricant percentage

COATING ISSUES Problems due to operating conditions + tablets characteristics • TWINNING: two tablets that stick together Common problem with flat or capsule-shaped tablets TWINNIN G

COATING ISSUES • TWINNING: two tablets that stick together Common problem with flat or capsule-shaped tablets This problem appears when there are large surfaces of between tablets.

CAUSE -HIGH SURFACE BETWEEN THE TABLETS -SPRAY RATE TOO HIGH -OVERWETTING -COATING DISPERSION TOO VISCOUS

SOLUTIONS -USE OTHER SHAPES OF TABLETS -DECREASE THE FLOW RATE -INCREASE THE TEMPERATURE OF THE TABLET BED -INCREASE THE SPEED PAN -DECREASE THE VISCOSITY OF THE COATING DISPERSION

COATING ISSUES Problems due to tablets characteristics and defects

• PEELING: the coating peels away from the tablet surface P EELI N G

COATING ISSUES Problems due to tablets characteristics and defects • PEELING: the coating peels away from the tablet surface CAUSES -POOR ADHESION OF FILM TO TABLET SURFACE

SOLUTIONS -USE SEPIFILM RANGE WITH MCC TO INCREASE THE FILM ADHESION -MODIFY THE LUBRICANT IN THE TABLETS FORMULA

COATING ISSUES Problems due to tablets characteristics and defects • CRACKING: Torn or cracked films CRACKI N G

COATING ISSUES Problems due to tablets characteristics and defects • Torn or cracked films CAUSE

-EXCESSIVE MOISTURE INTO THE CORES DURING THE COATING PROCESS SWELLING OF THE CORES -FILM WITH LOW ELASTICITY

SOLUTIONS

-REDUCE THE COATING FLOW RATE -USE SEPIFILM LP RANGE -USE FILM WITH HIGH LEVEL OF PLASTICIZER -DECREASE THE LEVEL OF INSOLUBLE COMPONENTS IN THE FILM

COATING ISSUES Problems due to tablets characteristics and defects • Blow-out of tablets/ capping: the tablet separates in laminar fashion CAP P I N G

COATING ISSUES Problems due to tablets characteristics and defects • Blow-out of tablets/ capping

CAUSE

SOLUTIONS - INCREASE THE LEVEL OF BINDER

- POOR LEVEL OF BINDER IN THE TABLETS FORMULATION

- REDUCE THE PAN SPEED - USE SEPIFILM LP TO IMPROVE THE LEVEL OF HARDNESS OF THE TABLETS

Be careful not to over-dry the tablets in the preheating stage. That can make the tablets brittle and promote capping.

CONCLUSION

CONCLUSION FILM COATING IS A SENSITIVE BALANCE BETWEEN « WETTING » AND « DRYING OF THE CORES »

APPENDIX 1

APPENDIX 1

EXERCISES 

3 kg of tablets need to be film coated for a stability study. – Weight of a tablet: 500 mg. Hardness = 140 N. Friability : < 0.1 %. – Weight of 20 uncoated tablets before introduction into the pan: 10.050 g – Weight gain: 4% w/w – Solids content: 12% w/w – Coating materials: 60% SEPIFILM™ LP 014 + 40% SEPISPERSE™ Dry 3232 Yellow

1.

Calculate the quantity of coating dispersion to be Note: Allow a 10% margin to compensate losses.

prepared.

2.

Calculate the quantity of SEPIFILM™/SEPISPERSE™ Dry and water to use.

APPENDIX 1 3.

The weight of 20 tablets film coated with 2% theoretical weight gain is 9.980 g. Calculate the actual weight gain. How can this result be explained?

4.

The lab. parameters for a 50 cm pan were as follows: – Load = 3 kg; Tinlet air = 70 °C; rotation =15 rpm; 1 gun; flow rate 9 g/min. When scaled up to an industrial unit on a 120 cm pan, the following parameters have been used: – Load = 100 kg; Tinlet air = 60 °C; rotation = 6 rpm; 4 guns Questions: – Why is the inlet air temperature set at a lower value? – Why is the pan rotation speed much slower?

5.

What spray flow rate do you suggest?

6.

A large quantity of dust is generated during the temperature rise. What do you suggest?

APPENDIX 1 1.

Calculate the quantity of coating dispersion to be prepared. Note: Allow a 10% margin to compensate losses. mcores  3000 g WG  4% mcoating  mcores  WG mcoating  3000  0.04 mcoating  120 g mcoating % solids  12% mdispersion  % solids 120 mdispersion  0.12 mdispersion  1000 g Losses :  10%

1100 g of dispersion to prepare

APPENDIX 1 2.

Calculate the quantity of SEPIFILM™/SEPISPERSE™ Dry and water to use.

 1100 g

Reminder : mdispersion

to prepare

Water : 88 %

mwater  1100  0.88  968 g

Coating : 12 % - 40% S episperse Dry 3232 Yellow → m dry 3232  0.40  m dispersion

to prepare

mdry 3232  0.40  1100  0.12 mdry 3232  52 .8 g - 60% S epifilm LP 014 → m LP014  0.60  m dispersion

to prepare

 % solids

mLP014  0.60  1100  0.12 mLP014  79 .2 g

 % solids

APPENDIX 1 3.

The weight of 20 tablets film coated with 2% theoretical weight gain is 9.980 g. Calculate the actual weight gain. m20 cores  10 .050 g m20 film coated tablets  9.980 g m 20 film coated tablets - m 20 cores 9.980 - 10 .050 WGactual   ≈ - 0.007 m n cores 10 .050 WGactual  - 0.7%

How can this result be explained? Water has evaporated from the tablets. To remedy this, measure the weight after the temperature increase and dust removal and not before placing them in the pan. If there is too much abrasion, work with the theoretical WG only, and not with the actual WG obtained by weighing the tablets.

APPENDIX 1 4.

Questions: – Why is the incoming air temperature set at a lower value? – Why is the pan rotation speed much slower? The air treatment system very often has much higher performance on industrial machines: high air flow rate, sometimes dehumidification. The tangential speed depends on pan diameter:

Vtangential  Vangular  R To maintain t he same tangentia l speed in two pans of different radius R and R : R  Vangular R Example : 2 R  50 cm, 2R  120 cm V angular  0.42  Vangular If Vangular  15 rpm V angular  6 rpm

V'angular

What do we do in the real life ? We adjust the speed by looking at the tablet bed surface.

APPENDIX 1 5.

Questions: – What spray flow rate do you suggest? As a rough estimate, the spray flow rate is in the region of 2 g/min/kg of tablets. 100 kg  flow rate = 200 g/min For this transposition, there are 4 guns. The recommended flow rate per gun is thus 50 g/min/gun. Experience is the only guide to optimizing the flow rate setting. The flow rate used on the lab. equipment was 9 g.min-1 / 3 kg = 3 g. min-1.kg-1  If one use the same flow rate of 3 g/min/kg for the industrial batch (i.e. 300 g/min), there is a risk of over-wetting. Indeed, the bed surface does not proportionally increase versus pan load. Important: The constancy of the temperature of the tablet bed is the only parameter governing the flow rate. Start at 25 g/min/gun, i.e. 100 g/min, then adjust during the process.

APPENDIX 1

6.

A large quantity of dust is generated during the temperature increase. What do you suggest? Work at negative pressure