Resveratrol Nanocrystal Incorporated into Mesoporous Material: Rational Design and Screening through Quality-by-Design Approach.

Ahmad Ainurofiq,Eva Y P Lestari,Mayasri M W Kumalasari,Yuniawan Hidayat,Syaiful Choiri

doi:10.3390/nano12020214

Abstract

Bioflavonoids from grape seeds feature powerful antioxidant and immunostimulant activities, but they present problems related to solubility and bioavailability. Nanocrystal (NC) incorporated into a mesoporous carrier is a promising strategy to address these issues. However, the preparation of this formulation involves the selection of factors affecting its critical quality attributes. Hence, this study aimed to develop an NC formulation incorporating resveratrol into a soluble mesoporous carrier based on rational screening design using a systematic and continuous development process, the quality-by-design paradigm. A mesoporous soluble carrier was prepared by spray-drying mannitol and ammonium carbonate. The NC was obtained by introducing the evaporated solvent containing a drug/polymer/surfactant and mesoporous carrier to the medium. A 26−2 fractional factorial design (FFD) approach was carried out in the screening process to understand the main effect factors. The type and concentration of polymer and surfactant, resveratrol loading, and solvent were determined on the NC characteristics. The results indicated that drug loading, particle size, and solubility were mainly affected by RSV loading, PEG concentration, and Kolliphor EL concentration. The polymer contributed dominantly to reducing the particle size and enhancing solubility in this screening design. The presence of surfactants in this system made it possible to prolong the supersaturation process. According to the 26−2 FFD, the factors selected to be further developed using a statistical technique according to the quality-by design-approach, Box Behnken Design, were Kolliphor EL, PEG400, and RSV loading.

Highlights

Antioxidant and immunostimulant activities have been the subject of increasing interest in recent years
A fractional factorial design was successfully applied for screening design in the preparation of NC incorporated into mesoporous mannitol containing RSV
The interactions between the factors could not be studied simultaneously due to the efficiency process in the screening design

Summary

Introduction

Antioxidant and immunostimulant activities have been the subject of increasing interest in recent years. These activities have received significant consideration, for the preventive and curative treatment of the Coronavirus disease, 2019 (COVID-19) [1,2]. Bioflavonoids were reported that were proven to be antioxidant and immunostimulant agents [3,4,5]. The improvement of several conditions, such as hypertension, hyperlipidemia, diabetes mellitus, cancer, cardiovascular diseases, neurodegeneration, aging, and antiviral and antibacterial properties, is affected by these activities. Further development of bioflavonoids is a promising candidate for the prevention and the improvement of the condition of COVID-19 patients [5,6]. Drug development and discovery, as well as paradigm-shifting through

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