Formulation of minitablets with personalised dissolution profile by fluid-bed granulation of drug nanosuspensions

Transforming poorly soluble active pharmaceutical ingredients (APIs) into a nanoparticulate form is a proven way of improving their dissolution characteristics. The preparation of API nanosuspensions is commonly achieved by wet-stirred media milling. The challenge lies in converting the nanosuspension into a solid dosage form without compromising its re-dispersibility. In the present work, an API nanosuspension was combined with additional excipients and used as abinder in fluid-bed granulation to obtain granules with systematically varying dissolution properties. Specifically, polymeric excipients (hydroxypropyl methylcellulose grade E5 and polyvinylpyrrolidone grade K30) were used in the nanosuspension binder to granulate microcrystalline cellulose or Pearlitol CR-H substrate. The resulting granules were used as feed material to prepare minitablets whose combination enabled the formation of multi-unit dosage form (MUDF) capsules with tuneable drug release profiles, paving the way to rational design and manufacturing of precision medicines.