title: Preparation and evaluation of solid dispersions of a new antitumor compound based on early-stage preparation discovery concept.
abstract: Ensuring sufficient drug solubility is a crucial problem in pharmaceutical-related research. For water-insoluble drugs, various formulation approaches are employed to enhance the solubility and bioavailability of lead compounds. The goal of this study was to enhance the dissolution and absorption of a new antitumor lead compound, T-OA. Early-stage preparation discovery concept was employed in this study. Based on this concept, a solid dispersion system was chosen as the method of improving drug solubility and bioavailability. Solid dispersions of T-OA in polyvinylpyrrolidone (PVP) K30 were prepared by the solvent evaporation method. Dissolution testing determined that the ideal drug-to-PVP ratio was 1:5. X-ray diffraction, Fourier transform infrared spectroscopy, and differential scanning calorimetry were employed to confirm the formation of solid dispersions. Scanning electron microscopy demonstrated that T-OA was converted into an amorphous form. Both in vitro dissolution testing and the in vivo studies demonstrated that the solubility and bioavailability of T-OA were significantly improved when formulated in a solid dispersion with PVP. The dissolution rate of the T-OA/PVP solid dispersion was greatly enhanced relative to the pure drug, and the relative bioavailability of T-OA solid dispersions was found to be 392.0%, which is 4-fold higher than the pure drug.
authors: School of Chinese materia medica, Bejing University of Chinese Medicine, Beijing, 100102, People's Republic of China.
authors: Peng
authors: P
authors: Hou
authors: Jian
authors: J
authors: Ni
authors: Sali
authors: S
authors: Cao
authors: Haimin
authors: H
authors: Lei
authors: Zhengjun
authors: Z
authors: Cai
authors: Tao
authors: T
authors: Zhang
authors: Fang
authors: F
authors: Yu
authors: Qingzhong
authors: Q
authors: Tan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D055808:Drug Discovery / Q000379:methods; D008297:Male; D008855:Microscopy, Electron, Scanning; D009828:Oleanolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry* / Q000493:pharmacokinetics; D011205:Povidone / Q000737:chemistry; D011719:Pyrazines / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013678:Technology, Pharmaceutical / Q000379:methods; D014961:X-Ray Diffraction
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D011719:Pyrazines; D009828:Oleanolic Acid; D011205:Povidone
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