Pharmaceutical nanoparticle isolation using CO₂-assisted dynamic bed coating

Poor solubility of new chemical entities (NCEs) is a major bottleneck in the pharmaceutical industry which typically leads to poor drug bioavailability and efficacy. Nanotechnologies offer an interesting route to improve the apparent solubility and dissolution rate of pharmaceutical drugs, and processes such as nano-spray drying and supercritical CO₂-assisted spray drying (SASD) provide a route to engineer and produce solid drug nanoparticles. However, dried nanoparticles often show poor rheological properties (e.g. flowability, tabletability) and their isolation using these methods is typically inefficient and leads to poor collection yields. The work presented herein demonstrates a novel production and isolation method for drug nanoparticles using a ‘top spray dynamic bed coating’ process, which uses CO₂ spray as the fluidizing gas. Nanoparticles of three BCS class II Active Pharmaceutical Ingredients (APIs), namely carbamazepine (CBZ), ketoprofen (KET) and risperidone (RIS), were produced and successfully coated onto micron-sized microcrystalline cellulose (MCC) particles. The size distribution of the API nanoparticles was in the range of 90–490 nm. The stable forms of CBZ (form III), KET (form I), and the metastable form of RIS (form B) were produced and coated onto MCC carrier microparticles. All the isolated solids presented optimal rheological properties along with a 2–6 fold improvement in the dissolution rate of the corresponding APIs. Hence, the ‘top spray dynamic bed coater’ developed in this work demonstrates to be an efficient approach to produce and coat API nanoparticles onto carrier particles with optimal rheological properties and improved dissolution.