Impact of Matrix Surface Area on Griseofulvin Release from Extrudates Prepared via Nanoextrusion

Abstract

We aimed to examine the impact of milling of extrudates prepared via nanoextrusion and the resulting matrix surface area of the particles on griseofulvin (GF, a model poorly soluble drug) release during in vitro dissolution. Wet-milled GF nanosuspensions containing a polymer (Sol: Soluplus®, Kol: Kolliphor® P407, or HPC: Hydroxypropyl cellulose) and sodium dodecyl sulfate were mixed with additional polymer and dried in an extruder. The extrudates with 2% and 10% GF loading were milled–sieved into three size fractions. XRPD–SEM results show that nanoextrusion produced GF nanocomposites with Kol/HPC and an amorphous solid dispersion (ASD) with Sol. For 8.9 mg GF dose (non-supersaturating condition), the dissolution rate parameter was higher for extrudates with higher external specific surface area and those with 10% drug loading. It exhibited a monotonic increase with surface area of the ASD, whereas its increase tended to saturate above ~30 × 10−3 m2/cm3 for the nanocomposites. In general, the nanocomposites released GF faster than the ASD due to greater wettability and faster erosion imparted by Kol/HPC than by Sol. For 100 mg GF dose, the ASD outperformed the nanocomposites due to supersaturation and only 10% GF ASD with 190 × 10−3 m2/cm3 surface area achieved immediate release (80% release within 30 min). Hence, this study suggests that ASD extrudates entail fine milling yielding > ~200 × 10−3 m2/cm3 for rapid drug release, whereas only a coarse milling yielding ~30 × 10−3 m2/cm3 may enable nanocomposites to release low-dose drugs rapidly.

Nanoseeded Desupersaturation and Dissolution Tests for Elucidating Supersaturation Maintenance in Amorphous Solid Dispersions

“…Clearly, they were not effective nucleation inhibitors. These findings agree with those in other studies in the literature [ 13 , 55 ].…”

Kinetic Modeling to Explain the Release of Medicine from Drug Delivery Systems

“…Spray-drying (chitosan-graphene oxide) [14] Freeze-drying (Sulfasalazine-chitosan) [15] Vacuum-drying (Itraconazole) [16] Aerosol flow reactor (glucocorticosteroid) [17] Electrospraying (Medroxyprogesterone acetate -PLA) [18] Fluid-bed coating/granulation/drying (Indomethacin) [19] Wet-casing drying (Sunitinib-PHBV) [20] Nanoextrusion (Griseofulvin) [21] Precipitation methods Solvent-antisolvent (Glibenclamide-HPMC) [22] High-gravity precipitation (Sorafenib) [23] Flash precipitation (soybean protein) [24] Sonocrystallization (Nobiletin) [25] Confined impinging liquid jet precipitation (loratadine) [26] Multi-inlet vortex mixing (lysozyme and erythromycin) [27] Sono precipitation (Clotrimazole, Isradipine) [28,29] Supercritical fluid precipitation (Rosuvastatin calcium) [30] Top-down High-pressure homogenization Microfluidification (Gadolinium diethylenetriamine penta-acetic acid) [31] Piston gap homogenization Bead milling (Griseofulvin -hydroxypropyl cellulose and sodium dodecyl sulfate) [32] Cryomilling (Phenytoin-PVP) [33] magnitude proportional to the concentration gradient and characterizing solute behavior, and Fick's second law, which predicts the effect of diffusion on varying concentrations. One can classify solute diffusion as either Fickian or non-Fickian, into one of which drug delivery systems frequently fall.…”

Hot-Melt Extrusion: from Theory to Application in Pharmaceutical Formulation—Where Are We Now?

“…The die was kept at 160 °C. In this setting, the removal of water was in the mixing zones, where the vent ports are kept open [23].…”