Angelica gigas Nakai and Soluplus-Based Solid Formulations Prepared by Hot-Melting Extrusion: Oral Absorption Enhancing and Memory Ameliorating Effects.
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.
School of Bioscience and Biotechnology, Kangwon National University, Chuncheon, 200-701, Republic of Korea.
Jingpei
J
Piao
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 151-742, Republic of Korea.
Jae-Young
JY
Lee
Department of Medical Biomaterials Engineering, College of Biomedical science, Kangwon National University, Chuncheon, 200-701, Republic of Korea.
Jin Bae
JB
Weon
Department of Medical Biomaterials Engineering, College of Biomedical science, Kangwon National University, Chuncheon, 200-701, Republic of Korea; Research Institute of Biotechnology, Kangwon National University, Chuncheon, 200-701, Republic of Korea.
Choong Je
CJ
Ma
College of Pharmacy, Kangwon National University, Chuncheon, 200-701, Republic of Korea.
Hyun-Jeong
HJ
Ko
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 151-742, Republic of Korea.
Dae-Duk
DD
Kim
School of Bioscience and Biotechnology, Kangwon National University, Chuncheon, 200-701, Republic of Korea.
Wie-Soo
WS
Kang
College of Pharmacy, Kangwon National University, Chuncheon, 200-701, Republic of Korea.
Hyun-Jong
HJ
Cho
D000284:Administration, Oral; D029969:Angelica / Q000737:chemistry*; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D004195:Disease Models, Animal; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects*; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy; D051379:Mice; D010316:Particle Size; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats
D010936:Plant Extracts