(645b) Scaling up and Optimization of Process Parameters for a Spray Drying Plant Using Mechanistic Modelling

Scaling up and optimization of
process parameters for a spray drying plant using mechanistic modelling

Sridevi Challa, Mohammed Yakoob
Sardar, Veera Pratap Reddy Kasina, RaviChandra Palaparthi, Srividya
Ramakrishnan, Ravikumar Gorle

Generic pharmaceutical industry has to operate in tight
timelines of product development and scale up from lab to plant where time to
market makes or breaks the viability of the business case. Getting it right the
first time demands detailed product & process understanding and
implementing appropriate mechanistic modelling and Quality-by-design (QbD)
approaches in the product life cycle, to minimize downstream risks especially
with the complexity of the formulations increasing exponentially in the current
decade for the generic industry. This work describes an example case of such
efforts on a model system comprising of excipients/ API involving the scale up
of spray drying operation from lab to plant scale.

Typical requirements in spray drying operations involve: identifying
the process conditions at one scale where one can minimize the right residual
solvent content and maximize the yield of the spray dried powder; translating
the process conditions as the product goes from lab to plant scale spray dryers.
A combination of experimental studies that characterize the relevant material
and lab/ plant equipment properties, and mechanistic models that link these
properties, and the process conditions to the final product quality (figure 1)
is expected to facilitate the scale-up. The broader spray dryer configuration (closed
loop/open loop, Figure 2) determines the type of process conditions to be
accounted for (i.e., those of the atomizer, the actual spray drying section,
cyclone separator, condenser and utilities).

Figure 1: Interactions
of different process and product parameters impacting spray dryer product
quality

Figure 2: Spray dryer
configuration (a) Closed loop; (b) Open loop

Ref: Modelling of a spray drying
process, Poul Bach, Martin Norby, Mark Pinto, Sean Bermingham,  2011, AICHE Annual Meeting ,Minneapolis, MN

The first part of this work shows how detailed
experimentation can help quantify the relevant material properties and the
spray dryer equipment characteristics. The second part focuses on leveraging a
combination of process flow sheeting type of a model, along with detailed
computational fluid dynamic simulations of the spray dryer chamber for
understanding the interactions of the various inputs on the product quality (figure
3). The CFD simulations help in addressing challenges due to changes in
geometry going from lab to plant scale spray dryers. The last part shows how
this understanding helped in scaling up from 1 l/hr to 50 l/hr evaporating capacity
spray dryer.

 Figure 3 Coupling framework of CFD-Process
flow sheeting model