Recent process in wet granulation

Wet granulation is the widely used technique and the granules are produced by wet massing of the excipients and API with granulation liquid with or without binder. Wet granulation has witnessed various technical and technological innovations such as steam granulation, moisture-activated dry granulation or moist granulation, thermal adhesion granulation, melt granulation, freeze granulation, foamed binder or foam granulation, and reverse wet granulation.

Reverse wet granulation or reverse-phase wet granulation is a new development in the wet granulation technique that involves the immersion of the dry powder formulation into the binder liquid followed by controlled breakage to form granules. The binder solution was prepared initially and the dry powder excipients were added to the binder solution under mixing in granulator. Alternatively, the drug was mixed with a solution of hydrophilic polymer and/or binder to form a drug-polymer/binder slurry as a granulating fluid. Granules were then formed by immersing a mixture of other dry excipients into the drug-polymer/binder slurry. The resulted wet granules were milled after drying. The granules produced by this process were found to have good flow and handling characteristics like those produced with wet granulation process. In addition, tablets formed from these granules eroded more uniformly during dissolution testing as compared to usual wet granulation technique.

Controlled breakage was proposed to be the predominant granule formation mechanisms in reverse wet granulation technique. It is purported that this technique improves the dissolution characteristics of the poorly water-soluble drugs by allowing uniform distribution of the binder that acts as a wetting agent and enable adequate wetting of the drug substance during granulation. It also increases the chances of adequate and uniform contact between the drug and hydrophilic polymer for better dissolution. These improved granule characteristics result in even erosion of tablets during dissolution.

The advantages of this technique over conventional wet granulation include small and spherical-shaped granules with improved flow properties, uniform wetting and erosion of the granules. This technique could be suitable for poorly water-soluble drugs because of the intimate association between a drug and the polymer. Usability of currently available equipment such as High Shear Mixer Granulator is another merit of this technique. However, this technique produced granules with a greater mass mean diameter and lower intragranular porosity when compared to the conventional wet granulation at lower binder concentrations.