Granulation of hydrophobic powders

Abstract

Granulation of hydrophobic powders is frequently required in the pharmaceutical industry. The structural complexity of new drug molecules mean that is increasingly common for entire classes of drug compounds to be highly hydrophobic. This creates considerable difficulty in understanding, controlling and trouble-shooting these industrial granulation processes.

There have been many recent advances in granulation theory. Essential to this theory is that wetting and spreading of the fluid through the powder particles is a prerequisite for good granulation. The possibility of a fine, hydrophobic powder spreading over the surface of the liquid during nucleation has been identified theoretically based on surface chemistry and as a potential nucleation mechanism. Recently, investigation confirmed that nucleation can occur by spreading of the sub-micron particles around the template drop to form a “liquid marble”. The hollow granule structure formed by the “solid-spreading” nucleation mechanism suggests the possibility of using the controlled, open granule structure to manufacture designer structured agglomerates with advantageous properties, including controlled granule structure and size and excellent ideal flow and handling properties. This paper describes single drop solid-spreading nucleation experiments where single fluid droplets are placed onto loosely packed powder beds of hydrophobic powders and the formation of the powder shell observed. Experimental results and observations for some model systems are presented, together with a preliminary framework for liquid marble formation.

Introduction

Wet granulation is a particle size enlargement process where small particles are agglomerated using a liquid binder to form larger granules. Traditional reasons for granulating a material include improving flow and handling properties, increasing bulk density, reducing dust formation, and reducing segregation of materials [1]. More recently, granulation is motivated by a desire to design structured agglomerates for specialty products such as pharmaceuticals, controlled dissolution detergents and “instant” food powders such as sauces [2]. Problems during granulation of specialty products can cause enormous downstream processing problems and product that does not meet regulatory and quality specifications.

Great progress has being made in understanding and controlling granulation mechanisms (e.g. [3], [4], [5], [6]) focusing on producing granules with a consistent, reproducible size distribution. This understanding has been applied to many industrial granulation processes, including pharmaceuticals [7], and detergents [8], [5] to improve their performance. However, granulation of poorly wetting powders has not been addressed in the above works but is commonly performed in pharmaceutical, minerals and fertilizer granulation.

Granulation of hydrophobic powders is frequently required in the pharmaceutical industry. The structural complexity of new drug molecules mean that is increasingly common for entire classes of drug compounds to be poorly wetting (contact angles approx 70–90°) or highly hydrophobic (contact angle ≥ 90°). The poor wetting properties can create considerable difficulty in understanding, controlling and trouble-shooting these industrial granulation processes.

A surfactant is often added to the granulation fluid and/or powders to improve the wetting characteristics of the formulation but this is not possible in some applications such as iron ore granulation or certain pharmaceutical formulations due to either the cost of the surfactant or chemical interactions that may occur. For these industries, the current body of granulation theory is often not applicable, as it is inherently assumed in all current granulation research that the liquid must wet the powder in order for granulation to be successful. We review below the state of knowledge of hydrophobic powder granulation.