23-Sep-2010 1 ISPE - Pellet Coating Process D. W. Staggs Fluid - PowerPoint PPT Presentation

23-Sep-2010 1 ISPE - Pellet Coating Process D. W. Staggs

Fluid Bed Pellet Coating Process: An Exercise in Process Engineering Fundamentals Darrell Staggs, P.E. Associate Engineering Consultant Process Engineering Center

Coated Pellet Formulation 23-Sep-2010 3 ISPE - Pellet Coating Process D. W. Staggs

Understanding the Process Technology The pellets are spray-coated with layer after layer of other materials, including API, while being blown around inside the MP10, a large stainless-steel vessel that works something like a giant hot-air corn popper , said Nic Chornet , team leader for manufacturing at IndyDry. MQ News 23-Sep-2010 4 ISPE - Pellet Coating Process D. W. Staggs

Fluidized Bed Pellet Coating The Basics 23-Sep-2010 5 ISPE - Pellet Coating Process D. W. Staggs

Define the Process Critical Process Parameters • Suspension T, Mill Speed, Product T during Coating Everything Else • Solution / Suspension Preparation • Air Preparation and Delivery • Solution / Suspension Delivery • Droplet Formation • Pellet Transport and Coating • Film Formation and Drying • Pellet Classification • … 70+ Variables 23-Sep-2010 6 ISPE - Pellet Coating Process D. W. Staggs

The Mass Balance Solids Applied Water Evaporation Coating Efficiency Pellet Potency 23-Sep-2010 7 ISPE - Pellet Coating Process D. W. Staggs

Pellet Coating Layers A Consistent Quality Product Sugar Core API Subcoat Enteric Color Analysis of Spheres SEM and Image Analysis Eric Olson 6/30/03 23-Sep-2010 8 ISPE - Pellet Coating Process D. W. Staggs

Pellet Coating Integrated Unit Operations Suspension Makeup Baghouse Pump Skid Filter Skid Coater CIP System 23-Sep-2010 9 ISPE - Pellet Coating Process D. W. Staggs

DEFINE the Process Process Thermodynamics - A ir Preparation and Drying Psychrometric Chart % % % 0 0 0.0340 8 0 4 6 = = = H H H 0.0320 R R R 0.0300 Humidity Ratio (kg H2O per kg dry air) 0.0280 0.0260 Exhaust h = 90 kJ/kg ⎯⎯→ 0.0240 40 C 48% RH 0.0220 0.0200 h = 70 kJ/kg ⎯⎯→ Drying 0.0180 30 C RH = 20% 0.0160 60% RH y f 0.0140 i d t p i h = 50 kJ/kg ⎯⎯→ m w 0.0120 u e h d e 0.0100 D C 8 Heat 0.0080 h = 30 kJ/kg ⎯⎯→ Inlet 0.0060 80 C 0.0040 0.0020 0.0000 0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100 Dry Bulb Temperature (C) 23-Sep-2010 10 ISPE - Pellet Coating Process D. W. Staggs

Process Thermodynamics- Increased Inlet Air T Psychrometric Chart % % % 0 0 0.0340 8 0 4 6 = = = H H H 0.0320 R R R Exhaust 0.0300 Humidity Ratio (kg H2O per kg dry air) 40 C 60% RH 0.0280 0.0260 h = 90 kJ/kg ⎯⎯→ 0.0240 0.0220 Drying 0.0200 h = 70 kJ/kg ⎯⎯→ 0.0180 30 C RH = 20% 0.0160 60% RH y f 0.0140 i d t p i h = 50 kJ/kg ⎯⎯→ m w 0.0120 u e h d e 0.0100 D C 8 Heat 0.0080 h = 30 kJ/kg ⎯⎯→ 0.0060 Inlet 95 C 0.0040 0.0020 0.0000 0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100 Dry Bulb Temperature (C) 23-Sep-2010 11 ISPE - Pellet Coating Process D. W. Staggs

Process Thermodynamics- Favorable Coating Conditions vs. System Capacity Psychrometric Chart % % % 0 0.0340 0 8 0 4 6 = = = H H H R 0.0320 R R 0.0300 0.0280 0.0260 Humidity Ratio (kg H2O per kg dry air) h = 90 kJ/kg ⎯⎯→ AHU + Coating 0.0240 95 Inlet, 8 D.P. 0.0220 0.0200 h = 70 kJ/kg ⎯⎯→ 0.0180 RH = 20% 0.0160 0.0140 h = 50 kJ/kg ⎯⎯→ 0.0120 0.0100 0.0080 h = 30 kJ/kg ⎯⎯→ 0.0060 0.0040 0.0020 0.0000 0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100 Dry Bulb Temperature (C) 23-Sep-2010 12 ISPE - Pellet Coating Process D. W. Staggs

Process Thermodynamics: Conclusions Evaporative Capacity AND Relative Humidity Environment Increase with increasing Inlet Temperature BUT, That does NOT fully define the coating environment. 23-Sep-2010 13 ISPE - Pellet Coating Process D. W. Staggs

Sustain the Process Equipment Qualification How to QUALIFY a Precision Coater™? All Columns performing equally • Air Flow Distribution • Atomization Air Control • Spray Rate Control • Temperature Response 23-Sep-2010 14 ISPE - Pellet Coating Process D. W. Staggs

Temperature Mapping a Precision Coater™ 100 95 Column Inlet T 90 TC1 85 TC2 vs . Inlet Air T TC3 TC4 80 TC5 Temp, C vs . Set Point TC6 75 TC7 TC8 vs. Time 70 TC9 TC10 65 Setpoint Inlet Temp 60 96 95.5 55 TC1 95 TC2 50 94.5 TC3 9:10:05 9:38:53 10:07:41 10:36:29 11:05:17 11:34:05 12:02:53 TC4 Time 94 TC5 93.5 Temp, C TC6 93 TC7 92.5 TC8 Column Inlet T TC9 92 TC10 91.5 Variability Setpoint 91 TT5209B 90.5 90 13:14:53 13:17:46 13:20:38 13:23:31 13:26:24 13:29:17 13:32:10 13:35:02 13:37:55 Time 23-Sep-2010 15 ISPE - Pellet Coating Process D. W. Staggs

Coating=Active Control Chart Individual Measurement of Oversize Pellets, kg Oversize Pellets, kg D. W. Staggs 23-Sep-2010 The Problem: Pellet Agglomeration Improve the Process - Secondary Loop 100 110 120 130 140 150 160 10 20 30 40 50 60 70 80 90 0 CT506492 CT507303 DTS23810 DTS23818 CT507304 CT508801 7RA52 7RA53 7RA54 7RH05 7SG37 7RH06 7SG28 7SG29 7SG30 7SG31 7SG32 7SG33 7SG34 7SG35 7SG36 7SG38 8RD01 Lot 8RD02 8RD04 8RD05 ISPE - Pellet Coating Process 8RD30 8RF93 8RF94 8RF95 8RF96 8RF98 8RF99 8RH26 8RH28 8RF97 8RH29 8RH30 8RH31 8RJ82 8RL13 8RL14 8RL15 8RL53 8RL54 8RL55 Avg=16.82 UCL=56.54 16

Duloxetine Pellet Coating Process Pellet AGGLOMERATION Wet Pellets Inadequate Poor Spray Free Moisture Drying Large Droplets High Relative Diffusion Limiting Air Flow Humidity Spray Nozzle Atomization Air Slurry Properties Delivery System Water Leak Drying Curve Environment API High Spray Solids Condensation (compare to talc) Air distribution Rate Low Pressue Viscosity Concentration Bed vs. Column Low Exhaust Mis-Alignment variability Temperature Air flow mal- distribution Nozzle Tip Wear Outside Air Leak Data: control valve Insert size HPMC? UofC Spray tests clearance / shear Cold Surface Plate pluggage API solids prop's API solids prop's Low Flow Pellet Aeration Low Pellet Distribution Circulation column loading Fouled nozzle Tank/ Agitator Low Energy design / operation Input API solids prop's Solids "Flooded" Column UC spray data Air flow rate Particle Size Distribution Inlet Temperature Aspect Ratio Low initial temperature Crystal Habit and Morphology DWS 1-Sep-2004 Agglomeration Mechanisms rev-3.vsd 23-Sep-2010 17 ISPE - Pellet Coating Process D. W. Staggs

Spray Nozzle Testing Spray Using MP-10 Nozzle for API Solution Studies On The Spray Pattern of Nozzles Used In Niro MP-10 And MP-1 Precision Coaters November 12, 2004 J. Zhou Process Engineering Center 23-Sep-2010 18 ISPE - Pellet Coating Process D. W. Staggs

Improve the Process Pellet Agglomeration Fundamental Process Changes: • Atomization Air P Coating=Active Control Chart • Initial Inlet air T Individual Measurement of Oversize Pellets, kg • Initial Air Flow 160 150 140 130 120 110 Oversize Pellets, kg 100 90 80 70 60 UCL=56.54 50 40 30 20 Avg=16.82 10 0 CT506492 CT507303 DTS23810 DTS23818 CT507304 CT508801 7RA52 7RA53 7RA54 7RH05 7SG37 7RH06 7SG28 7SG29 7SG30 7SG31 7SG32 7SG33 7SG34 7SG35 7SG36 7SG38 8RD01 8RD02 8RD04 8RD05 8RD30 8RF93 8RF94 8RF95 8RF96 8RF98 8RF99 8RH26 8RH28 8RF97 8RH29 8RH30 8RH31 8RJ82 8RL13 8RL14 8RL15 8RL53 8RL54 8RL55 Lot 23-Sep-2010 19 ISPE - Pellet Coating Process D. W. Staggs

Process Engineering Fundamentals “There is no result in nature without a cause; understand the cause and you will have no need of the experiment. “ “Therefore O students study mathematics and to not build without foundations.” “He who thinks little makes many mistakes.” Leonardo Da Vinci 23-Sep-2010 20 ISPE - Pellet Coating Process D. W. Staggs

The Fluid Bed Pellet Coating Process Questions? 23-Sep-2010 21 ISPE - Pellet Coating Process D. W. Staggs