Pneumatic Dry Granulation


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Pneumatic Dry Granulation

  1. 1. Pneumatic Dry Granulation A dry process to improve oral formulation design time and resource requirements
  2. 2. <ul><ul><li>PDG is an innovative form of dry granulation with the same process up to Roller Compaction (RC) including the milling of flakes (ribbons) followed by a pneumatic classification process </li></ul></ul>PDG = P neumatic D ry G ranulation PDG Technology
  3. 3. <ul><li>Based on the PDG technology, Atacama provides: </li></ul><ul><li>the same capabilities as wet granulation without its disadvantages </li></ul><ul><li>Galenic development: </li></ul><ul><li>faster development (within weeks) even with difficult APIs </li></ul><ul><li>Production: </li></ul><ul><li>cheaper than wet granulation (30-40%), efficient and reliable, high throughput, continuous production, ability to treat difficult materials with a simple process </li></ul><ul><li>Commercial advantage: </li></ul><ul><li>Lower production costs (vs. wet granulation) </li></ul><ul><li>Life cycle management for extended market exclusivity of new galenic forms </li></ul><ul><li>Patient differentiation advantages: easier to swallow, faster effect, easier handling for added compliance </li></ul>Atacama advantages:
  4. 4. Technical advantages of PDG <ul><li>Excellent flowability and high compactibility of granules </li></ul><ul><li>Enables flexible high tablet drug load (70-95%) </li></ul><ul><li>Very fast development of new galenic formulation </li></ul><ul><li>Ability to develop substances with dry granulation otherwise not easily possible with wet granulation (heat labile, probiotic, moisture sensitive) </li></ul><ul><li>High production efficiency in terms of input/output ratio (less waste, less batches to discard) and throughput (vs. wet granulation) </li></ul><ul><li>Less costly in terms of simplicity, energy consumption, staff needed, excipients </li></ul><ul><li>PDG Granules can be also used for capsule filling </li></ul>
  5. 5. Commercial advantages <ul><li>Smaller tablets via higher drug load increasing patient compliance (swallowing, reduced dosing frequency) </li></ul><ul><li>Ideal for new fix-combinations </li></ul><ul><li>Fast disintegrating tablets (from 20 sec. onward depending on substance examples) due to porous granules </li></ul><ul><li>Marketing exclusivity through technology patents </li></ul><ul><li>Retained market share through differentiation (new galenic form, same) </li></ul><ul><li>Large production cost savings </li></ul>
  6. 6. <ul><li>Your situation: </li></ul><ul><li>Trend to replace wet granulation by dry granulation (OTC, Rx or Gx) </li></ul><ul><li>Need to develop difficult new APIs / formulations (mono, combi, ODT) </li></ul><ul><li>Steps: </li></ul><ul><li>Definition of: API properties / difficulties / safety data / target profile (client) </li></ul><ul><li>Feasibility study (2 weeks) for a very limited fixed fee (omitted if production contract), if successful: </li></ul><ul><li>Galenic development services for fixed fees </li></ul><ul><li>Contract manufacturing services for bulk or finished product costs </li></ul><ul><li>Possibility for higher volumes: installation of leased machinery equipment inhouse at client premises with longterm contract </li></ul>Business model
  7. 7. The technology in detail <ul><li>How it works </li></ul><ul><li>What it can do (examples: Avicel, Paracetamol) </li></ul>
  8. 8. Compactor (Gerteis MiniPactor) Cyclone Integrated Mill Fractionating Device Receiver Safety Filter Vacuum Pump Feeding container Service Area Recycling sequence Granules out API / Mix in PDG 0260 system: simple layout
  9. 9. Installation at Excella in Feucht Roller compactor (MiniPactor, Gerteis) Classinator (Atacama) Blend to be granulated recycled powder feed hopper Integrated mill PDG 0260 in cGMP environment
  10. 10. <ul><ul><li>Main differences compared to usual roller compaction processes are: </li></ul></ul><ul><ul><ul><li>Lowest possible compaction force as compared to standard dry granulation to preserve maximum binding capacity of the granules </li></ul></ul></ul><ul><ul><ul><li>New gas-flow based fractionating device , resulting in considerably less fines in the granulate ensuring excellent flowability </li></ul></ul></ul><ul><ul><ul><li>Pneumatic recycling for high process efficiency </li></ul></ul></ul><ul><ul><ul><li>Closed-loop system minimizing the leakage of dust </li></ul></ul></ul><ul><ul><li>The resulting granules are soft and porous, </li></ul></ul><ul><ul><li>very well flowable and with optimal recompactibility properties </li></ul></ul>PDG – what‘s new ?
  11. 11. Trial: RC vs. PDG <ul><li>Goal: </li></ul><ul><ul><li>to prove that both flowability and compactibility can be achieved with P neumatic D ry G ranulation </li></ul></ul><ul><ul><li>To provide a PD-G ranulated Paracetamol tablet with acceptable tablet profile </li></ul></ul><ul><li>Test candidates: </li></ul><ul><ul><li>Avicel PH105: MCC‘s are well known for loss in tablet bondability after roller compaction </li></ul></ul><ul><ul><li>Paracetamol: known for very low flowability and elastic recovery, difficult to tablet, high dose </li></ul></ul>
  12. 12. <ul><li>Compression Simulator </li></ul><ul><ul><li>STYLCAM (MEDELPHARM) </li></ul></ul><ul><ul><li>Single stroke press with adjustable cams </li></ul></ul><ul><ul><li>Used for simulating the speed of a Fette 102i during all compaction experiments in this study </li></ul></ul><ul><ul><li>Speed: 30% to 70% of a Fette 102i, EU-B </li></ul></ul><ul><ul><li>Precompaction force level was set to 0% (PH105) or 50% (PCM) of main compaction level </li></ul></ul><ul><ul><li>Manual die filling </li></ul></ul>Trial equipment for tableting
  13. 13. Force level (kN/cm): 1 PDG Force level (kN/cm): 5 RC only Force level (kN/cm): 11 RC only Roll gap (mm): 4 Speed (rpm): 5 Screen (mm): 1.25 Avicel PH105: trial settings
  14. 14. <ul><li>Roller compaction: Force: 1 kN/cm </li></ul><ul><ul><ul><li>Gap: 4 mm </li></ul></ul></ul><ul><ul><ul><li>Speed: 5 rpm </li></ul></ul></ul><ul><ul><ul><li>Screen: 1.25 mm </li></ul></ul></ul>PDG granulated Avicel PH105
  15. 15. PDG provides acceptable bonding WITH flowability ! Recompactibility of PDG granules
  16. 16. <ul><li>PDG -Granulate </li></ul><ul><ul><li>Excellent flowability </li></ul></ul><ul><ul><li>Hardly any loss in compactibility </li></ul></ul><ul><li>Roller compacted-Granulate </li></ul><ul><li>Poor flowability </li></ul><ul><li>Even at enlarged loss in compactibility </li></ul>Conclusion Avicel PH105
  17. 17. <ul><li>Pre-blend (before PDG granulation) </li></ul><ul><ul><li>94.1% Paracetamol (80 parts) </li></ul></ul><ul><ul><li> 5.9% Kollidon CL-M (5 parts) </li></ul></ul><ul><li>After-blend (after PDG granulation) </li></ul><ul><ul><li> 9.5 % PDG-granulated Avicel (PH105) </li></ul></ul><ul><ul><li> 5.0 % Klucel EXF </li></ul></ul><ul><ul><li> 0.5 % Magnesiumstearate </li></ul></ul><ul><li>Final tablet contains 80% of Paracetamol </li></ul>Paracetamol trial set-up
  18. 18. Avicel PH102 PDG granulate: PCM/CL-M =80/5 PDG granulate: final tablet mix PDG granules: flowability
  19. 19. Acceptable tensile strength PDG granules: compactibility
  20. 20. No capping at all PDG granules: no capping
  21. 21. PDG granules: dissolution
  22. 22. simulated tableting speed: 43000 tablets/hr (Fette 102i, 30 rpm), no sticking to punches observed PDG tablet properties: aspect Crushing Force (9mm concave tablets (rc=15 mm), 312.5 mg) Tensile Strength 62 N (no capping) 1.02 MPa Friability 0.27 % Disintegration < 60 s Dissolution (phosphate buffer) (water) 100% within 5 -10 min 100% within 15-20 min
  23. 23. Even a difficult-to-tablet material like Paracetamol results in a well flowable granulate/tableting mix and tablets, which are strong enough: 60N, low friability, no capping disintegrate rapidly: < 60 s dissolve rapidly: within 5 to 10 min (phosphate buffer) have high drug load: 80% (vs. max. 50% in RC) Conclusion PDG Paracetamol
  24. 24. Avicel PH105 Paracetamol PDG summary
  25. 25. Virtually every API, that in principle can be compacted, can also be PD-G ranulated ! The result is a flowable and compactable granulate ! PDG summary This extends the application of dry granulation enormously: PDG -technology now provides you with an excellent alternative to wet granulation without the disadvantages and being far more economical Contact us at for more results
  26. 26. Thank you for your kind attention !