QbD-based formulation development of resveratrol nanocrystal incorporated into soluble mesoporous material: Pharmacokinetic proof of concept study

Resveratrol (RSV) has powerful antioxidant activities. However, the bioavailability is still limited due to low solubility and transport issues. Nanocrystal technology has been introduced to address these issues; however, the bulky formulation of the nanocrystal process through nanosuspension faces a big challenge in terms of stability and scale-up ability. This work aimed to enhance the bioavailability of RSV through nanocrystal formulation incorporated into soluble mesoporous carriers for superior solid-state stability and feasibility.

This formulation was designed and developed rationally through scientific justification in the nanocrystal formulation along with quality by design paradigm. Box-Behnken design was applied to determine the optimized formulation based on the particle size and distribution, drug loading, zeta potential, and supersaturation parameters. The nanocrystal was formed through evaporation of drug, polymer, and surfactant in the solvent incorporated into mesoporous material. The nanocrystal was evaluated by vibrational spectroscopy, thermal analyses, and SEM and TEM photographs, followed by crystallinity evaluation.

The results indicated that the factors only affected the particle size variation, zeta potential, drug loading, and the time to reach the supersaturation peak level. The optimized formulation was achieved by 68 % desirability value, producing 133.3 ± 1.2 nm particle size and −24.6 mV zeta potential. The physical and chemical evaluation characterization indicated no interaction between RSV and carrier. In addition, there was no difference in crystallinity between the RSV nanocrystal and native RSV. Moreover, the RSV nanocrystal improved the bioavailability nearly twice compared to the RSV suspension.

Materials

RSV isolated and purified from Polygonum cuspidatum Sieb.Et Zucc (98,52 %; HPLC) was purchased from Thanen Chemicals (Changzhou, China). Kolliphor EL was obtained from BASF (Ludwigshafen, Germany). Polyethylene glycol (PEG) 400, methanol, and ammonium carbonate were purchased from Merck (Darmstadt, Germany). Mannitol was achieved from Roquette (Lestrem, France).

Ahmad Ainurofiq, Bingah Ginanjar Rahayu, Faradisania Adnan Murtadla, Ilham Kuncahyo, Anjar Windarsih, Syaiful Choiri, QbD-based formulation development of resveratrol nanocrystal incorporated into soluble mesoporous material: Pharmacokinetic proof of concept study, International Journal of Pharmaceutics, Volume 661, 2024, 124459, ISSN 0378-5173, https://doi.org/10.1016/j.ijpharm.2024.124459.