Drying in the

Pharmaceutical Industry
DIT- Msc Pharmaceutical and
Chemical Processes Technologies
28th April 2009
Sara Baeza

Drying in the Pharmaceutical Industry 1

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 2

Introduction
Drying 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 3

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 4

Introduction to Drying Process(contd)
• Periods of Drying

•Warm up period :A-B

•Constant Rate Period (B-C)
Critical
Moisture
 HT dependent
content
•Falling rate period (C-D)
 MT dependent

Drying in the Pharmaceutical Industry 5

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.

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Dryers in the Pharma Industry
Dryers 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 7

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 8
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 9
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 10

 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 11

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
 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 13

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 14

 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 15

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 16

 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 17

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)

Drying in the Pharmaceutical Industry 20

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

Drying in the Pharmaceutical Industry 22

References

 http://pubs.acs.org/doi/pdf/10.1021/op05
0091q
 http://books.google.co.uk

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