Dissolution of poorly soluble drugs can be improved by wet-milling their suspensions and drying the suspensions to form nanocomposites. Different classes of dispersants and their concentration can affect both nanoparticle aggregation in the suspensions and drug dissolution from the nanocomposites. In this study, we examine the impact of various classes of dispersants on nanoparticle aggregation–dissolution of itraconazole (ITZ) from spray-dried wet-milled ITZ nanosuspensions. 2.5% hydroxypropyl cellulose (HPC), 0.2% sodium dodecyl sulfate (SDS), and their combination were used as baseline dispersant formulations. Mannitol and sucrose, as model water-soluble dispersants, were added to the wet-milled ITZ suspensions with HPC. As swellable dispersants, superdisintegrants such as sodium starch glycolate (SSG), crospovidone (CP), and croscarmellose sodium (CCS) were wet-co-milled with ITZ–HPC. The wet-milled suspensions were spray-dried to prepare nanocomposites. Laser diffraction results show that wet milling with HPC–SDS and HPC with concentration at/above 4.5% led to a median drug size below ~0.20 μm due to electrosteric and steric stabilizing effects, respectively. Their nanocomposites led to immediate, fast ITZ release: >%80 dissolved in 20 min. Unlike these suspensions, other suspensions with mannitol, sucrose, and superdisintegrants along with HPC exhibited more aggregation and pseudoplasticity. Nonetheless, the addition of these dispersants resulted in faster drug release especially at higher concentrations, as quantified by the higher value of the product kn of the Korsmeyer–Peppas model, due to faster erosion/disintegration of the nanocomposite matrix. Wet co-milled superdisintegrants achieved faster drug release than mannitol and sucrose. Their dissolution impact was positively correlated with their swelling capacity (SSG > CCS > CP), which signifies a swelling-induced erosion/disintegration mechanism. Surfactant-free nanocomposites with >60% drug loading that exhibited immediate drug release were prepared with either HPC–co-milled SSG/CCS or HPC with optimal concentration.
All Science Journal Classification (ASJC) codes
- General Chemical Engineering
- Drug nanoparticles
- Spray drying
- Wet media milling
- Wet-milled superdisintegrants