Enhancing the oral bioavailability of baicalein via Solutol® HS15 and Poloxamer 188 mixed micelles system

Abstract

Objectives To increase the solubility of baicalein (BAI) by preparing BAI‐micelles (BAI‐M) with Solutol HS15 (HS15) and Poloxamer 188 (F68), thereby improving its oral bioavailability. Methods Baicalein micelles were prepared with HS15 and F68 by thin‐film dispersion method and optimized by central composite design (CCD) approach. Physicochemical, in vitro release, Caco‐2 cell transport and pharmacokinetic studies of BAI‐M were performed. Key findings The optimal formulation showed spherical shape by characterization of the transmission electron microscope with average small size (23.14 ± 1.46 nm) and high entrapment efficiency (92.78±0.98%) and drug loading (6.45±1.54%). The in vitro release study of BAI‐M showed a significantly sustained release pattern compared with free BAI. Caco‐2 cell transport study demonstrated that high permeability of BAI was achieved after loading it into micelles. Meanwhile, pharmacokinetics study of BAI‐M showed a 3.02‐fold increase in relative oral bioavailability compared with free BAI. Conclusions Based on our findings, we concluded that HS15 can be used as a carrier in this drug delivery system that includes F68, and BAI‐M has great potential in improving solubility and oral bioavailability.

Wedelolactone-Loaded Micelles Ameliorate Doxorubicin-Induced Oxidative Injury in Podocytes by Improving Permeability and Bioavailability

“…The low bioavailability of drugs due to poor absorption and water-insoluble properties limits their application in clinical contexts. Research suggests that about 40% of the marketed drugs and 90% of drug candidates exhibited poor absorption in the gastrointestinal tract due to poor water solubility, resulting in limited or poor efficacy (Shen et al, 2019). The in vivo behavior and bioavailability of these compounds could be influenced by both physicochemical and physiological factors (Upadhyay et al, 2012).…”

“…Solutol ® HS 15 was employed to enhance the stability of WED-M. A small proportion of the 12-hydroxyl group in the chemical structure of Solutol ® HS 15 can be etherified by polyethylene glycol. Under 25°C conditions, the stability of Solutol ® HS 15 can be maintained for 24 months (Shen et al, 2019). It is noteworthy that Solutol ® HS 15 does not show significant property alteration, even with hydrolysis at 121°C for 15 min.…”

Pharmacokinetics of B-Ring Unsubstituted Flavones

“…Baicalein (5,6,7-trihydroxy-flavone) has also low bioavailability, attributed to its poor water solubility [194], being a class IV compound in the Biopharmaceuticals Classification System (BCS) (solubility: 0.052 mg/mL in water; lipophilicity: Papp = 0.037 × 10 −6 cm/s) [195]. Despite its low solubility, the bioavailability of baicalein is still superior to that of baicalin when administered at equivalent doses in rats, when measuring the baicalin plasma concentration [196].…”

“…Despite its low solubility, the bioavailability of baicalein is still superior to that of baicalin when administered at equivalent doses in rats, when measuring the baicalin plasma concentration [196]. Many technological attempts have been made to improve the bioavailability of baicalein or baicalin: preparation of micelles with different excipients [194,197]; co-crystal formation with theophylline [198], nicotinamide [199], or other compounds [200]; co-precipitates with polyvinylpyrrolidone [201]; nanocrystals for oral or pulmonary administration [56,202,203,204]; nanoemulsions [205,206,207,208]; nanosuspensions [209]; nanoliposomes [210,211] and nanostructure lipid carriers [212,213]; self-assembled nanoparticles [214]; solid lipid nanoparticles [215]; solid dispersions with different excipients [216,217,218,219]; preparation of complexes with cyclodextrins [220]; and self-microemulsifying systems [221].…”

“…The volume of in vivo PK data is limited for this class of flavones, and data in humans are still more limited. Although baicalein has been reported in certain PK studies (e.g., [194]), other authors reporting such PK data have stated that “the content of baicalein cannot be detected after oral administration, the baicalin is predominant in the plasma when baicalein is administered orally, so baicalein absorption can be assessed by detecting the baicalin concentration and baicalein glycosides” [195].…”