Development of Orthosiphon stamineus ethanolic solid dispersions for solubility improvements of lipophilic flavones

Abstract

This study was conducted to develop an ethanolic solid dispersion of Orthosiphon stamineus (ESD) using polymers as carriers, namely polyvinylpyrrolidone (PVP), poloxamer 188 (P188), and poloxamer 407 (P407) via the solvent evaporation method. The purpose of preparing the formulation is to improve the solubility of the lipophilic flavones, namely sinensetin (SIN), eupatorine (EUP), and 3'-hydroxy-5, 6, 7, 4'-tetramethoxyflavone (TMF) and caffeic acid derivatives, namely rosmarinic acid (RA). The optimized ESD was characterized using High-Performance Liquid Chromatography (HPLC), Attenuated Total Reflection Fourier Transform Infrared (ATR-FTIR) fingerprints, and physicochemical methods (particle size, zeta potential, TEM, and SEM). The effect of pH on stability and solubility in buffer and water, invitro release, and antioxidant properties (DPPH assay) indicated that the nano-formulation ESD using polymers (PVP/P407) with a ratio of extract to polymers (1.0:1.1:0.3 w/w) enhanced the lipophilic flavones (TMF=3.56 ± 0.01% w/w, SIN=2.46 ± 0.01% w/w and EUP=7.87 ± 0.01% w/w) and RA (20.66 ± 0.01% w/w) compared to the same compounds in ethanolic extract (P< 0.0001) with particles size less than 200 nm. In conclusion, the successful development of ESD using water-soluble copolymers (PVP/P407) has enhanced the solubility of lipophilic flavones and other compounds (RA), thereby further improving its pharmacological properties.