10th International Granulation Workshop

Although the wet granulation process can be performed with different equipment, the use of high-shear mixers (HSMs) may offer many advantages. Among these, the most relevant is the possibility of performing all the granulation steps (mixing, wetting, and massing phases) on the same equipment, leading to a reduction in dustiness, risk of cross-contamination, and toxic exposure. However, in general, the drying phase is performed in other equipment to reduce the process time (fluid bed) or the cost (ventilated oven). However, drying can be performed in HSM if the instrument is equipped with a heating jacket and a vacuum pump. The purpose of this research is to evaluate the effect of the type of drying technique on the properties of granules and tablets. In particular, the two techniques evaluated were drying in a ventilated oven (D-O) or inside the HSG using the heating jacket and vacuum pump (D-J/V). The three formulations selected for this study contain: 40% (w/w) microcrystalline cellulose as granulation aid, 34% (w/w) lactose as diluent, 3% (w/w) polyvinylpyrrolidone K30 as binder, 3% (w/w) sodium starch glycolate as disintegrant and 20% (w/w) of three model molecules as actives (caffeine, paracetamol or citric acid). The actives are characterized by different water solubility and particle size. The study started with a rheological characterization performed using a mixer torque rheometer to identify the amount of water necessary for granulation and to predict the growth mechanism. Granules were produced following a standard procedure and dried in a ventilated oven set at 60°C or inside the HSM using the jacket temperature set at 60°C and a vacuum pressure of 200 mbar. The process was carried out until a LOD of 3% was reached. As expected, the data highlighted that D-J/V allows for a reduction in drying time ranging from 30 to 45%. The granules were then characterized by sieve analysis (PSD), content uniformity, flowability, tensile strength, and compression studies. The results showed that the granules obtained by D-J/V are generally smaller, with a higher yield and a lower crushing strength. As regards the granule structure, the data and SEM imagines show that the effect of the drying type depends on the solubility of the active; in fact, if the active is very soluble in water, faster migration and crystallization of the active can occur on the granule surface. Granules with a particle size <500 m were then compressed using different compression forces and tablets with a tensile strength of approximately 1 MPa were then characterized by mass and content uniformity tests, disintegration and dissolution tests. Results showed that compressibility, tabletability, and compactability of the granules were improved using D-J/V when the active was sparingly soluble in water, but the disintegration and dissolution performances were not modified. On the contrary, when a highly soluble active is present, D-O allows for an increase of compression properties owing to the crystals present on the surface, but it produces a drastic worsening of disintegration and dissolution performances.