Preparation of Multicomponent Fisetin‐Hydroxypropyl β Cyclodextrin‐Poloxamer Inclusion Complex by Microwave Technology

ABSTRACT Fisetin (FS) is a polyphenolic flavonoid possessing multiple biological activities along with broad nutraceutical applications. The low solubility of FS greatly limits its bioavailability and its use. The aim of the study was to prepare an FS ternary inclusion complex (TIC) using hydroxypropyl β‐cyclodextrin (HPβCD) and Poloxamer 188 (P188) by microwave technology. Phase solubility studies were performed in the presence of HPβCD (1 to 10 mM) and P188. The in vitro release of FS, ternary physical mixture (TPM) and FS‐TIC was determined. Additionally, DSC, FTIR, XRD, and SEM studies were performed on FS, TPM, and FS‐TIC to characterize the samples. Furthermore, FS‐TIC and pure FS were assessed for their antioxidant activity. The outcomes of the phase solubility study revealed that 6.33‐fold the solubility of FS was boosted in the presence of HPβCD/P188. FS and TPM demonstrated in vitro drug release of 34.09% and 62.29%, respectively. While a maximum in vitro drug release of 84.45% was obtained for FS‐TIC; this could be due to the formation of a water‐soluble inclusion complex. Results showed that FS release from TPM and TIC occurred through the Fickian diffusion mechanism and followed the Higuchi pattern. DSC, FTIR, XRD, and SEM analyses verified FS interaction with HPβCD and subsequently supported FS‐TIC formation. Furthermore, the developed FS‐TIC showed superior antioxidant activity compared to pure FS. It was concluded that the FS‐TIC prepared by microwave technique using HPβCD as a carrier provides a potential approach to facilitate FS solubility and drug release. In addition, microwave techniques combined with cyclodextrin/polymer properties present an intriguing approach to circumventing the solubility issue of poorly soluble compounds like fisetin.