Angelica gigas Nakai and Soluplus-Based Solid Formulations Prepared by Hot-Melting Extrusion: Oral Absorption Enhancing and Memory Ameliorating Effects

Abstract

Oral solid formulations based on Angelica gigas Nakai (AGN) and Soluplus were prepared by the hot-melting extrusion (HME) method. AGN was pulverized into coarse and ultrafine particles, and their particle size and morphology were investigated. Ultrafine AGN particles were used in the HME process with high shear to produce AGN-based formulations. In simulated gastrointestinal fluids (pH 1.2 and pH 6.8) and water, significantly higher amounts of the major active components of AGN, decursin (D) and decursinol angelate (DA), were extracted from the HME-processed AGN/Soluplus (F8) group than the AGN EtOH extract (ext) group (p < 0.05). Based on an in vivo pharmacokinetic study in rats, the relative oral bioavailability of decursinol (DOH), a hepatic metabolite of D and DA, in F8-administered mice was 8.75-fold higher than in AGN EtOH ext-treated group. In scopolamine-induced memory-impaired mice, F8 exhibited a more potent cognitive enhancing effect than AGN EtOH ext in both a Morris water maze test and a passive avoidance test. These findings suggest that HME-processed AGN/Soluplus formulation (F8) could be a promising therapeutic candidate for memory impairment.

Fabrication and Characterizations of Hot-Melt Extruded Nanocomposites Based on Zinc Sulfate Monohydrate and Soluplus

“…HME is a continuous manufacturing process that can be easily scaled up [7]. Materials can be thrown into the extruder, moved towards the die and homogeneously blended by rotating screws, and extruded from the die (or an orifice) [8][9][10][11]. During the HME process, the temperature of barrels is designed above the glass transition temperature (T g ) and sometimes over the melting temperature (T m ) of polymeric substances, and the drug can be molecularly dispersed in the polymer matrix [9,12,13].…”

Natural Korean Medicine Dang-Gui: Biosynthesis, Effective Extraction and Formulations of Major Active Pyranocoumarins, Their Molecular Action Mechanism in Cancer, and Other Biological Activities

“…AGNACCs D, DA and DOH are hydrophobic in nature and poorly solubilize in water, thus, diverse physical and chemical methods are employed for extraction of these compounds. Different methods and formulations have been exploited to enhance the extraction of therapeutically active compounds [ 28 , 29 ]. A colloidal diffusion with nanoparticles method was utilized to extract these compounds for oral administration in a therapeutic study [ 30 ].…”

Bio- Fortification of Angelica gigas Nakai Nano-Powder Using Bio-Polymer by Hot Melt Extrusion to Enhance the Bioaccessibility and Functionality of Nutraceutical Compounds

“…The moisture content of the sample was measured by the moisture meter, and between 2% and 3% of the moisture was used to measure the water-related parameters. The water absorption index (WAI), water solubility (WS), and swelling power (SP) were calculated by the following formulas described by Piao et al [21].…”

“…Amorphous nanoparticles exhibit very high saturation solubility compared to the crystalline form [36]. The HME tends to make more channels to enhance the permeability and penetration of water into the core of the matrix of the material [21]. The solubility of amorphous substances is higher than the thermodynamically stable crystalline forms, because their internal bonding forces are weak.…”

“…Moreover, Hagi and Hatami [53] showed that higher levels of flavonoid were produced with the use of an acid-mediated solution derived from vegetables and medicinal plants. The most likely explanation for the enhanced active-compound extraction from the extrudate sample is the disruption of the cell wall structure by the HME, which enables the easier extraction/release of phenolic compounds from samples, thus increasing the total number of phenolic compounds [21]. It is explained that due to hydrophilic characteristics and sol-gel behavior of the HPMC polymer, extraction was facilitated [54].…”