Spray Drying Scale-up Approaches Fundamentals and Case Studies. April 29 th, 2014

Transcription

1 Spray Drying Scale-up Approaches Fundamentals and Case Studies João Vicente APS Amorphous by Design April 29 th, 2014

2 Overview Spray Drying fundamentals Setting a stable lab scale process Scale-up methodology 2 João Vicente April 2014 Confidential Hovione 2014

3 Spray Drying How it works Feed atomization produces small droplets with the target size distribution Droplet evaporation takes place within the drying chamber contraction Dry product collection 3 João Vicente April 2014 Confidential Hovione 2014

4 Mechanistic approach Thermodynamics Feed Tank Drying chamber hot drying gas hot drying gas Cyclone wet gas to calculate of RS_out, T_dew, dgas detect abnormal conditions of operation a tool for development & scale-up Gas Recycling Unit Atomization a tool for scale-up to achieve target particle size distribution Drying chamber Cyclone wet gas Gas Recycling Unit Product (very fine particles) Drying Kinetics to control particle morphology to optimize powder performance identify pitfalls Product (very fine particles) 4 João Vicente April 2014 Confidential Hovione 2014

5 Thermodynamics Thermal conditions in a spray dryer are determined through heat and mass balance so that Q Q Q Q in feed loss out Q in F drying T in g i Cp i g i Q loss UA T out T room Q feed F feed l l 1 Cfeed i H i Cpi T b Tfeed i i Q out F drying T out g i Cp i g i y cond i Pv P i x i i 5 João Vicente April 2014 Confidential Hovione 2014

6 T_in (predicted) Thermodynamics If Q loss is known the model is scale and product independent Determination of T_out, T_dew and RS_out 200 Buchi B-290 Adv. Niro PSD1 Niro PSD % Portugal & USA Portugal & USA Portugal % Niro PSD3 Niro PSD4 Niro PSD5 80 y = 1.00x R² = 0.99 Portugal Portugal Ireland T_in (observed) 6 João Vicente April 2014 Confidential Hovione 2014

7 Atomization Considerable differences among published models Droplet size correlations based on experimental data (Phase Doppler Interferometer) are the most straightforward tools to generate the required data 7 João Vicente April 2014 Confidential Hovione 2014

8 Atomization Particle size is typically dictated by the droplet size Atomization model can be used to select the nozzle and atomization conditions that best suit the targets of particle size and process throughput 8 João Vicente April 2014 Confidential Hovione 2014

9 Drying Kinetics Fast drying promotes the production of spherical particles; Slow drying results in the production of shriveled particles; Solids concentration impacts shell flexibility Drying time depends on relative saturation and droplet size Bulk density is typically dependent on RS_out 9 João Vicente April 2014 Confidential Hovione 2014

10 Drying Kinetics Ballooning is associated with flexible polymers, dried at temperatures above boiling point Friable material may break when dried at high temperatures 10 João Vicente April 2014 Confidential Hovione 2014

11 Case-study Solids: API + HPMCP - Solvents: DCM and ethanol Data is available from trials executed in two different scales Particle size, bulk density and residual solvents predicted by scale-independent parameters 11 João Vicente April 2014 Confidential Hovione 2014

12 Overview Spray Drying fundamentals Setting a stable lab scale process Scale-up methodology 12 João Vicente April 2014 Confidential Hovione 2014

13 Setting a stable lab scale process Most relevant parameters for SD process Feed properties Feed chemical and physical stability Solvent system, concentration, viscosity, etc... Product attributes Stickness, tendency to agglomerate Residual solvents Chemical/physical stability, hygroscopicity, etc Process: Edge of failure Reprocessability Process yield Ability to post-dry the SD powders Where everything starts! 13 João Vicente April 2014 Confidential Hovione 2014

14 Setting a stable lab scale process Solution stability - Temperature Affects surface tension / viscosity / density and therefore droplet size Seldom used to optimize powder properties Strict control is required when operating close to solubility limits Often used to increase chemical stability 14 João Vicente April 2014 Confidential Hovione 2014

15 Setting a stable lab scale process Solids concentration Large effect on particle size and process throughput. Avoid extremely viscous feeds since they are difficult to atomize Stay away from saturation limit (target 80-85%) m (cp) C_feed (%) T_feed (ºC) 15 João Vicente April 2014 Confidential Hovione 2014

16 Setting a stable lab scale process Summary (Lab-scale work) Set a process stable at lab conditions (assure good atomization and select adequate T_in, T_out) Select T_feed based on feed stability and control it during scale up Select C_feed to maximize throughput but avoid very viscous solutions and keep some distance from saturation. Once the process seems stable, run it with extended processing time; check the yield and the occurence of bearding problems Use a close-loop system to get representative values for the residual solvents; evaluate the feasibility of the solvent/post-drying step 16 João Vicente April 2014 Confidential Hovione 2014

17 Scale-Up Taking advantage of scale-up to optimize powder properties Buchi B290/295 (two-fluid nozzle) Niro PSD4 (pressure nozzle) D v 50 = 2.4 mm span = 2.6 bulk density = 0.19 g/ml D v 50 = 70 mm span = 1.6 bulk density = 0.35 g/ml 17 João Vicente April 2014 Confidential Hovione 2014

18 Scale-Up Method Similar powder properties can also be obtained at different scales ProCepT Micro-Spray (ultrasonic nozzle) Niro PSD4 (pressure nozzle) D v 50 = 83 mm span = 1.5 bulk density = 0.34 g/ml tap density = 0.42 g/ml solvent = 7% w/w D v 50 = 82 mm; span = 1.7 bulk density = 0.29 g/ml tap density = 0.40 g/ml solvent = 5% w/w 18 João Vicente April 2014 Confidential Hovione 2014

19 Overview Spray Drying fundamentals Setting a stable lab scale process Scale-up methodology 19 João Vicente April 2014 Confidential Hovione 2014

20 What is important in scaling-up? Nozzle and process conditions Thermal conditions Atomization / Droplet size Dew point Bearding Product attributes Particle size Bulk density Glass transition temperature (Tg) Solvent content Spray plume Yield 20 João Vicente April 2014 Confidential Hovione 2014

21 Tg and solvent content The relation of Tg with RS_out enables the anticipation of the impact of the spray drying operating conditions on the SDD amorphous stability 21 João Vicente April 2014 Confidential Hovione 2014

22 Solvent content and residence time The extended residence time in larger units provides a safety margin Drying curve determined at lab scale can be considered the worst case scenario 22 João Vicente April 2014 Confidential Hovione 2014

23 Scale-up Thermodynamic space Conservative approach: Maintain relative saturation Consider equipment and process limitations 23 João Vicente April 2014 Confidential Hovione 2014

24 Scale-up Atomization Droplet Size (mm) Feed Flow (kg/h) Use droplet size correlations to select the nozzle Pressure (bar) Droplet Size 61/21 Feed Flow 61/21 24 João Vicente April 2014 Confidential Hovione 2014

25 Typical challenges Atomization issues Yield/agglomeration/stickness Bearding Chemical stability / degradation Solvent condensation 25 João Vicente April 2014 Confidential Hovione 2014

26 Conclusions Useful information can be gathered in laboratorial work minimizing the use of large scale testing Powder properties can be well described through scale independent parameters With the right tools, scale up can be a straightforward and predictable task 26 João Vicente April 2014 Confidential Hovione 2014

27 Thank you for your attention João Vicente Drug Product Development João Vicente April 2014 Confidential Hovione 2014