drying in the pharmaceutical industry1 dit- msc pharmaceutical and chemical processes technologies...

Drying in the Pharmaceutical Industry 1

Drying in the Pharmaceutical

Industry

DIT- Msc Pharmaceutical and Chemical Processes Technologies

28th April 2009Sara Baeza


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.


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


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


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


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.


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


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


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


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



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




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


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




Crystal breakage was observed during early stages of the dryingNo significant breakage was observed afterwards


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




Small crystal breakage was observed during early stages of the dryingNo significant breakage was observed afterwards


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




No crystal breakage was observed during early stages of the dryingNo significant breakage was observed afterwards


Case StudyDevelopmental work conclusions


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)


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


Q&A


References

http://pubs.acs.org/doi/pdf/10.1021/op050091q

http://books.google.co.uk

drying in the pharmaceutical industry1 dit- msc pharmaceutical and chemical processes technologies...

Documents

drying process

process drying

drying equipment

drying step

pharmaceutical process

loss of drying lod

rotary dryers

api process