Drying in the Pharmaceutical Industry

1. Drying in the Pharmaceutical Industry DIT- Msc Pharmaceutical and Chemical Processes Technologies 28th April 2009 Sara Baeza Drying in the Pharmaceutical Industry

2. Agenda • Introduction to Drying in the Pharmaceutical Industry. • Introduction to the Drying process. • Dyers selection for a Pharmaceutical process. • Case Study: Trouble shouting the drying step and its impact on formulation. Drying in the Pharmaceutical Industry

3. IntroductionDrying in Pharmaceutical Industry • Drying APIs is an important operation for the production of consistent, stable, free-flowing materials for formulation, packaging, storage and transport • Particle attrition or agglomeration can result in major differences in particle size distribution (PSD), compressibility and flow characteristics • Equipment selection • Drying specifications Drying in the Pharmaceutical Industry

4. Introduction to Drying Process • Drying can be described by three processes operating simultaneously: • Energy transfer from an external source to the water or organic solvent • Direct or Indirect Heat Transfer • Phase transformation of water/solvent from a liquid-like state to a vapour state • Mass Transfer (solid characteristics) • Transfer vapour generated away from the API and out of the drying equipment Drying in the Pharmaceutical Industry

5. Introduction to Drying Process(contd) • Periods of Drying • Warm up period :A-B • Constant Rate Period (B-C) • HT dependent • Falling rate period (C-D) • MT dependent Critical Moisture content Drying in the Pharmaceutical Industry

6. Dryers in the Pharma Industry • Dryers can be classified according to: • Heat transferring methods • Direct: Fluidised, Tray, Spray, Rotary Dryers, etc.. • Indirect: Cone, Tumble, Pan Dryers, etc… • Continuous/ Batch processing • Continuous: large quantities/small residence time • Batch: small quantities/ long residence time • Method of handling the solids. Drying in the Pharmaceutical Industry

7. Dryers in the Pharma IndustryDryers classification • Material Handling- API physical characteristics • Flowability: • Charging/discharging of product • Attrition/agglomeration • Control PSD and its impact on formulation • Bulk density • Batch size • Temperature stability • Melting point • Friction (agitator/discharging) • Polymorphic shifts • Containment • Isolation & Drying equipment combined • Glove box Drying in the Pharmaceutical Industry

8. Case Study - Background • Expand/back up dryer capability for API process • Past development work concluded that API dried in high shear dryers lead to crystal attrition which was shown to adversely affect the formulation process and thus the drug performance • Limited low shear dryers (cone dryer) availability • Excellent high shear (Filter & Pan) Dryers availability Drying in the Pharmaceutical Industry

9. Case study – Developmental work • Characterization of attrition/agglomeration suffered by API in high shears dryers such as FDR and PDR • Characterize particle size (PSD) during drying by tracking Lasentec profiles in the dryer with time • Correlate the loss of drying (LOD) with PSD • Effect of Dryer agitation on attrition/agglomeration • Physical characteristics of API comparable to conical dried material Drying in the Pharmaceutical Industry

10. Case study – Developmental work • Lab size jacketed FDR Rosenmound with variable agitation to induce varying degree of breakage while monitoring attrition with Lasentec • PSD for Conical dried material: • Mean sq wt range= 60-80 • median no wt range= 10-20 Drying in the Pharmaceutical Industry

11. Case study – Developmental work • Experiment 1: • 1 kg of wet API • Initial LOD 25% • Jacket Tem @ 55C • Total drying time 1 h • Continuous agitation 50 rpm during the drying Drying in the Pharmaceutical Industry

12. Case study – Developmental work Crystal breakage was observed during early stages of the drying No significant breakage was observed afterwards (LOD=2.5%) PSD not comparable to conical dryer material Drying in the Pharmaceutical Industry

13. Case study – Developmental work • Experiment 2: • 1 kg of wet API • Initial LOD 25% • Jacket Tem @ 55C • Total drying time 3 h • Intermittent agitation at 50 rpm, intervals of 5 min, applied during the first 1 h (LOD=2.4 %) • After 1h, continuous agitation at 50 rpm Drying in the Pharmaceutical Industry

14. Case study – Developmental work Crystal breakage was observed during early stages of the drying No significant breakage was observed afterwards Drying in the Pharmaceutical Industry

15. Case study – Developmental work • Experiment 3: • 1 kg of wet API • Initial LOD 25% • Jacket Tem @ 55C • Total drying time 4.5 h • No agitation during first 1.5 h (LOD = 4 %) • After 1.5 h, intermittent agitation at 50 rpm for 10 min every 10 min Drying in the Pharmaceutical Industry

16. Case study – Developmental work Small crystal breakage was observed during early stages of the drying No significant breakage was observed afterwards Drying in the Pharmaceutical Industry

17. Case study – Developmental work • Experiment 4: • 1 kg of wet API • Initial LOD 25% • Jacket Tem @ 55C • Total drying time 5.5 h • No agitation during first two hours (2.5 %LOD) • After two hours, intermittent agitation at 5 rpm for 6 min every hour Drying in the Pharmaceutical Industry

18. Case study – Developmental work No crystal breakage was observed during early stages of the drying No significant breakage was observed afterwards Drying in the Pharmaceutical Industry

19. Case StudyDevelopmental work conclusions Drying in the Pharmaceutical Industry

20. Case StudyDevelopmental work conclusions • FDR experiments produced comparable PSD material to conical dried material • The more rapid and aggressive agitation corresponded directly to an increased amount of attrition in the filter dried product • Particle breakage occurred in the early stages if the drying and was minimal in the late stages of the drying (wetness dependent) Drying in the Pharmaceutical Industry

21. Case StudyFollow up • Conservative drying regime for manufacturing FDR was designed and scaled up based on the developmental experiments results obtained in lab FDR • Trial batch produced material that preformed successfully in the formulation site • Drying regime optimization and implementation currently on going Drying in the Pharmaceutical Industry

22. Q&A Drying in the Pharmaceutical Industry

23. References • http://pubs.acs.org/doi/pdf/10.1021/op050091q • http://books.google.co.uk Drying in the Pharmaceutical Industry