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Drying in the Pharmaceutical Industry 1
Drying in the Pharmaceutical
Industry
DIT- Msc Pharmaceutical and Chemical Processes Technologies
28th April 2009Sara 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:1. Energy transfer from an external source to the
water or organic solvent Direct or Indirect Heat Transfer
2. Phase transformation of water/solvent from a liquid-like state to a vapour state
Mass Transfer (solid characteristics)
3. Transfer vapour generated away from the API and out of the drying equipment
Drying in the Pharmaceutical Industry 5
Introduction to Drying Process(contd)
•Warm up period :A-B
•Constant Rate Period (B-C)
HT dependent
•Falling rate period (C-D)
MT dependent
• Periods of Drying
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
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
Case study – Developmental work
Drying in the Pharmaceutical Industry 11
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
Case study – Developmental work
Drying in the Pharmaceutical Industry 12
Case study – Developmental work
Crystal breakage was observed during early stages of the dryingNo significant breakage was observed afterwards (LOD=2.5%)PSD not comparable to conical dryer material
Drying in the Pharmaceutical Industry 13
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
Case study – Developmental work
Drying in the Pharmaceutical Industry 14
Case study – Developmental work
Crystal breakage was observed during early stages of the dryingNo significant breakage was observed afterwards
Drying in the Pharmaceutical Industry 15
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
Case study – Developmental work
Drying in the Pharmaceutical Industry 16
Case study – Developmental work
Small crystal breakage was observed during early stages of the dryingNo significant breakage was observed afterwards
Drying in the Pharmaceutical Industry 17
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
Case study – Developmental work
Drying in the Pharmaceutical Industry 18
Case study – Developmental work
No crystal breakage was observed during early stages of the dryingNo 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
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