Transcript Slide 1

Drying in the
Pharmaceutical Industry
DIT- Msc Pharmaceutical and
Chemical Processes Technologies
28th April 2009
Sara Baeza
Drying in the Pharmaceutical Industry
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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.
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Drying in the Pharmaceutical Industry
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Introduction
Drying in Pharmaceutical Industry
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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
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Introduction to Drying Process
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Drying can be described by three
processes operating simultaneously:
1.
Energy transfer from an external source to the
water or organic solvent
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2.
Phase transformation of water/solvent from a liquidlike state to a vapour state
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3.
Direct or Indirect Heat Transfer
Mass Transfer (solid characteristics)
Transfer vapour generated away from the API and
out of the drying equipment
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Introduction to Drying Process(contd)
•
Periods of Drying
•Warm up period :A-B
•Constant Rate Period (B-C)
Critical
Moisture
content
 HT dependent
•Falling rate period (C-D)
 MT dependent
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Dryers in the Pharma Industry
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Dryers can be classified according to:
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Heat transferring methods
 Direct: Fluidised, Tray, Spray, Rotary Dryers, etc..
 Indirect: Cone, Tumble, Pan Dryers, etc…
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Continuous/ Batch processing
 Continuous: large quantities/small residence time
 Batch: small quantities/ long residence time
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Method of handling the solids.
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Dryers in the Pharma Industry
Dryers classification
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Material Handling- API physical characteristics
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Flowability:
 Charging/discharging of product
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Attrition/agglomeration
 Control PSD and its impact on formulation
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Bulk density
 Batch size
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Temperature stability
 Melting point
 Friction (agitator/discharging)
 Polymorphic shifts
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Containment
 Isolation & Drying equipment combined
 Glove box
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Case Study - Background
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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
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Case study – Developmental work
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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
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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
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Case study – Developmental work
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Experiment 1:
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1 kg of wet API
Initial LOD 25%
Jacket Tem @ 55C
Total drying time 1 h
Continuous agitation 50 rpm during the drying
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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
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Case study – Developmental work
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Experiment 2:
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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
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Case study – Developmental work
Crystal breakage was observed during early stages of the drying
No significant breakage was observed afterwards
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Case study – Developmental work
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Experiment 3:
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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
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Case study – Developmental work
Small crystal breakage was observed during early stages of the drying
No significant breakage was observed afterwards
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Case study – Developmental work
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Experiment 4:
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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
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Case study – Developmental work
No crystal breakage was observed during early stages of the drying
No significant breakage was observed afterwards
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Case Study
Developmental work conclusions
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Case Study
Developmental 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)
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Case Study
Follow 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
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Q&A
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References
http://pubs.acs.org/doi/pdf/10.1021/op05
0091q
 http://books.google.co.uk
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