Development and characterization of resveratrol dry emulsions using Quality-by-Design approach

Abstract

Resveratrol (RVT) possesses various potential advantages to human health. However, RVT has some disadvantages i.e. poor water solubility and photo-sensitivity. The aims of this research were to improve the dissolution property and photostability of RVT. Spray-dried emulsion and emulsion-loaded porous powders were developed to encapsulate RVT. The dissolution and photostability of RVT in the spray-dried emulsion and porous powders were significantly improved, compared to intact RVT. Quality-by-Design (QbD) approach, which emphasizes product and process understanding based on science and risk management, was implemented to provide an extensive understanding of the relationship between product and process factors and responses. In the development of RVT spray-dried emulsion, the possible risks were evaluated in risk assessments, including the Ishikawa diagram and a risk-ranking system. The critical factors were further revealed in a Plackett–Burman design. After the experiment, the risks were re-evaluated based on new understanding. The low-methoxyl pectin (LMP) amount, caprylic/capric glyceride (CCG) amount, homogenization speed, and pump speed were observed to most critically affect the quality of the product and the spray-drying performance. The spray-dried emulsions and spray-drying process were optimized using Box-Behnken design to produce RVT spray-dried emulsion having small redispersed emulsion size, fast dissolution, good flow property, and desirable spraying efficacy. The experimental results have shown that the size of redispersed emulsion was influenced by LMP and CCG amount. The dissolution rate was influenced by CCG. The angle of repose of RVT spray-dried emulsion was influenced by LMP and CCG amount. The spraying efficiency was enhanced due to an increase in pump speed. The optimized formulation containing 2.75% w/w of LMP and 7% w/w of CCG sprayed with pump speed of 10.1 mL/min prepared within design space met satisfy criteria. In the development of RVT-loaded onto porous calcium silicate (PCS) powders, the effects of LMP, ethyl acetate (EA) and RVT to PCS ratio (RVT:PCS) on drug loading capacity, encapsulation efficiency, and drug dissolution were investigated and optimized using Box-Behnken design. EA amount and RVT:PCS had significant effect on the drug loading capacity. The encapsulation efficiency was significantly influenced by EA amount. The RVT:PCS had a significant effect on drug dissolution. The RVT-PCS powders formulation was optimized for achieving high loading capacity, encapsulation efficiency, and rapid drug dissolution. An optimized RVT/PCS powders containing 2.2% w/w LMP, 14% w/w EA and RVT:PCS at 0.15:1 prepared within the design space satisfied all criteria. The RVT products were successfully developed and optimized by implementing the QbD approach.

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