Improved solubility, dissolution rate, and oral bioavailability of main biflavonoids from Selaginella doederleinii extract by amorphous solid dispersion

Abstract

2020) Improved solubility, dissolution rate, and oral bioavailability of main biflavonoids from Selaginelladoederleinii extract by amorphous solid dispersion, Drug Delivery, 27:1, 309-322, ABSTRACT Amentoflavone, robustaflavone, 2 00 ,3 00 -dihydro-3 0 ,3 000 -biapigenin, 3 0 ,3 000 -binaringenin, and delicaflavone are five major hydrophobic components in the total biflavonoids extract from Selaginella doederleinii (TBESD) that display favorable anticancer properties. The purpose of this study was to develop a new oral delivery formulation to improve the solubilities, dissolution rates, and oral bioavailabilities of the main ingredients in TBESD by the solid dispersion technique. Solid dispersions of TBESD with various hydrophilic polymers were prepared, and different technologies were applied to select the suitable carrier and method. TBESD amorphous solid dispersion (TBESD-ASD) with polyvinylpyrrolidone K-30 was successfully prepared by the solvent evaporation method. The physicochemical properties of TBESD-ASD were investigated by scanning electron microscopy, differential scanning calorimetry, and Fourier-transform infrared spectroscopy. As a result, TBESD was found to be molecularly dispersed in the amorphous carrier. The solubilities and dissolution rates of all five ingredients in the TBESD-ASD were significantly increased (nearly 100% release), compared with raw TBESD. Meanwhile, TBESD-ASD showed good preservation stability for 3 months under accelerated conditions of 40 C and 75% relative humidity. A subsequent pharmacokinetic study in rats revealed that C max and AUC 0-t of all five components were significantly increased by the solid dispersion preparation. An in vivo study clearly revealed that compared to raw TBESD, a significant reduction in tumor size and microvascular density occurred after oral administration of TBESD-ASD to xenograft-bearing tumor mice. Collectively, the developed TBESD-ASD with the improved solubility, dissolution rates and oral bio-availabilities of the main ingredients could be a promising chemotherapeutic agent for cancer treatment. ARTICLE HISTORY

Therapeutic Applications of Solid Dispersions for Drugs and New Molecules: In Vitro and In Vivo Activities

“…To overcome these difficulties, Chen et al [ 53 ] prepared a solid dispersion of TBESD with the polymer PVP K30 (TBESD-SD) by the solvent evaporation method. To assess the in vivo antitumor effect, mice with xenograft of A549 cells derived from human alveolar basal epithelial cell adenocarcinoma were treated with doses of 200 mg/kg TBSED and TBESD-SD and 2 mg/kg doxorubicin.…”

<p>Improvements in the Oral Absorption and Anticancer Efficacy of an Oxaliplatin-Loaded Solid Formulation: Pharmacokinetic Properties in Rats and Nonhuman Primates and the Effects of Oral Metronomic Dosing on Colorectal Cancer</p>

“…44 Furthermore, inclusion of bile acids in the formulation inhibits crystallization and stabilizes the formulation. 13,45 For these reasons, the amorphous form of ODSF and its reduced particle size, compared to OP/DLM, confirm the physical state of the formulation.…”

“…5,7,8 Notably, several novel strategies are currently under investigation to overcome these challenges and improve oral bioavailability. [9][10][11][12][13] Platinum-based chemotherapeutics are the cornerstones of cancer treatment and have been widely used in clinical practice. The third-generation platinum analogue, oxaliplatin (cis-[(1R,2R)-1,2-cyclohexanediamine-N,N'] [oxalato(2)-O,O´] platinum; OP) is used for the treatment of advanced colorectal cancer.…”

Novel Solid Dispersions of Naphthoquinone Using Different Polymers for Improvement of Antichagasic Activity

“…There was also no endothermic event related to IVS320 in the IVS320-PVP SDs (Figure 3d); this indicates that the IVS320 was converted into an amorphous state, thus justifying its dispersion in the polymeric carrier. However, the exothermic event was found at 200 °C in the IVS320-PVP/KN SD and at 198 °C in the IVS320-PVP/RE SD [33].…”