Wet Granulation Process via Foams and Drops

Wet granulation using foaming binder solution is a new approach of liquid delivery to create granules. This study compares wet granulation via foamed binder addition method and sprayed binder addition method by studying the kinetics of foam and drop penetrations into loosely packed powder beds. Foam and drop nucleation kinetics were compared by examining specific penetration time (penetration time per unit mass of liquid drop or foam) and nucleation ratio (ratio of mass of nuclei granules to mass of liquid binder). The mechanisms of foam decay such as liquid drainage and bubble coalescence are critical to the process of foam penetration into the powder pores. Foam penetration rate cannot be completely revealed until the foam characteristics are clearly determined. Nucleation ratio results suggest that foam nucleation method allows more efficient liquid usage and liquid distribution to induce nucleation of powder compared to drop nucleation method. INTRODUCTION A new liquid delivery method – foam granulation has been developed as an alternative to the traditional application of atomized liquid spray in pharmaceutical wet granulation processes. Unlike spray granulation, the liquid binder is sent through a foam generator and distributed to the powder bed as aqueous foam to induce granulation. This novel approach has been shown to produce granules and tablets in the pharmaceutical processing. Initial experiments indicate that foam granulation uses less liquid binder; discards the need for nozzles which subsequently eliminates the problems associated with nozzles; and has better liquid dispersion and wetting through the powder mass (Keary and Sheskey, 2004). Scale-up studies has also demonstrated the technical operating potential of this technology (Sheskey, et al., 2007). Research on foam granulation technology has focused on a series of foam granulation industrial case studies (Keary and Sheskey, 2004). However, there is still lack of understanding on how nucleation and granulation occur when foamed addition method is used. This paper investigates the penetration kinetics of foam by depositing a single foams on a loosely packed powder bed, and it was compared to that of using single drops of the same fluid. The nucleation kinetics of foams and drops are compared by examining the penetration time and nucleation ratio. Both parameters are useful in quantifying the liquid distribution efficiency and the nuclei formation kinetics (Hapgood, et al., 2002, Schaafsma, et al., 2000). The penetration time is defined as the time required for a drop or foam to completely penetrate into the powder bed. Studying the penetration kinetics of liquid can be useful to understanding nucleation kinetics (Hapgood, et al., 2002). Due to variations of foam mass dispersed, specific penetration ( p t ), defined as the penetration time ( p t ) per unit mass of binder (m) is introduced in this study: