Formulation of Ketoconazole Nanocrystal-Based Cryopellets.

Commercial development of nanosuspensions for oral drug delivery generally involves a drying step which aims to generate a stable product that rapidly releases the nanocrystals once rehydrated and can be easily processed into a final dosage form (e.g., filled into hard capsule).

Nanocrystals of a potent p38 MAPK inhibitor embedded in microparticles: Therapeutic effects in inflammatory and mechanistic murine models of osteoarthritis.

This study aimed to formulate nanocrystal-polymer particles (NPPs) containing the potent p38α/β MAPK inhibitor PH-797804 (PH-NPPs) and to test their extended-release properties over months in comparison to those of conventional PH microparticles for the intra-articular treatment of inflammatory and mechanistic murine models mirroring aspects of human osteoarthritis (OA). The steps of the study were (i) to formulate PH nanocrystals (wet milling), (ii) to encapsulate a high payload of PH nanocrystals in fluorescent particles (spray drying), (iii) to assess in vitro drug release, (iv) to evaluate PH-NPP toxicity to human OA synoviocytes (MTT test), (v) to investigate the in vivo bioactivity of the particles in mice in an inflammatory antigen-induced arthritis (AIA) model (using histology and RT-qPCR) and (vi) to investigate the in vivo bioactivity of the particles in the OA model obtained by mechanistic surgical destabilization of the medial meniscus (DMM) (using histology, micro-CT, and multiplex ELISA). The PH nanocrystals stabilized with vitamin E TPGS had a monomodal size distribution.

Active freeze drying for production of nanocrystal-based powder: A pilot study.

Active Freeze Drying allows for producing lyophilised powders by progressive agitation of frozen blocks undergoing sublimation. One potential application of this process is the formulation design of unstable nanosuspensions for oral drug delivery, as here shown for nanocrystal-based ketoconazole powder. With this technique, a critical vapour flow needs to be achieved in order to obtain reasonable process yields (>78%).