(465c) Model Based Approach to Determine Optimum Operating Conditions in High Shear Granulation

This work is a part of FDA sponsored project that is carried out by Members of the National Institute for Pharmaceutical Technology and Education (NIPTE). The aim of the project is to develop Quality by Design (QbD) guidance elements on process design space, scale-up, and process validation for three unit operations: mixing, granulation, and drying; and to develope a framework for optimizing design space specification across scales with consideration to stability. The specific aim of this work is to implement scientific improvements to high shear wet granulation to determine the best operation window on a laboratory scale granulation system for a pharmaceutical formulation. The key dimensionless groups and regime maps developed from these dimensionless groups in the last decade are used to determine the regime of operation which will provide desired granule characteristics. Dimensionless groups, namely dimensionless spray flux (a), dimensionless penetration time (p), maximum liquid saturation (Smax) incorporate both formulation properties and process parameters. The formulation characteristics including particle size, true density, tap density, penetration time of binder into powder surface; and the process characteristics including powder surface velocity, binder drop size, circulation time in the granulator, flow rate of the liquid binder are determined, initially. Gabapentin is used as the active pharmaceutical ingredient and water is used as the liquid binder. The granulation formulation also consists of hydroxylpropylcellulose (HPC). This work consists of two parts. In the first part, laboratory scale experiments are designed and performed based on regime maps to determine good operating conditions as well as to show extreme operating conditions in Diosna (6 l) high shear granulator. In the second part, another granulator system (Gral) is investigated by using the same formulation. By keeping the dimensionless groups constant, the knowledge on Diosna granulator is transferred to Gral granulator. The process characteristics of the new system are explored to combine them with formulation properties in order to get the same product characteristics as it is obtained in Diosna.