(233am) Modeling and Simulation Efforts in Scale up of Sustained Release Microspheres

Abstract

Generic
pharmaceutical industry has to operate in tight timelines of product
development and scale up from lab to plant. To meet such needs, Dr Reddys
Laboratories use approaches like modeling and simulation for better process
understanding and to reduce scale up risks. This presentation provides example
cases of such efforts in a microspheres product.

Microencapsulation
process development demands understanding of the impacts of various material
properties and process parameters to achieve the right product characteristics.
Employing appropriate modeling approaches at different scales can aid in
developing this understanding. In this work, a first principle based diffusion
model which uses Monte Carlo simulation helps link the impact of microsphere
product attributes like size distribution, porosity, and polymer properties on
the sustained release of drug from microspheres.[1] Results from a numerical simulation of this model gauge the
risk of each of the product characteristics on the release. This understanding
identifies the key product attributes to focus on and manipulate with the
process conditions.

Manufacture
of such micro-encapsulated products consists of multiple unit operation steps
like phase separation, extraction and drying to get the desired product
characteristics. A combination of first principle, and CFD based approaches for
the unit operations links how each of the process steps impacts the product
attributes. Some of the important linkages made include scale dependent variations
of: mixing conditions on particle size using vessel averaged Reynolds and Weber
number obtained from CFD simulations; cycle times for extractions by single
particle spherical diffusion model; and drying cycle predictions by first
principle discrete element model with mixing simulated by randomization of the
discrete elements. Custom lab scale experimentation provides the necessary
model parameters and enables extension of the understanding towards the plant
scale. This provides the necessary framework for a successful scale-up.

[1] J.
Siepmann, N. Faisant, J.P. Benoit, A new mathematical model quantifying drug
release from bioerodible microparticles using Monte Carlo simulations,
Pharm.Res. 19 (2002) 1885–1893.