Preparation，physicochemical properties and pharmacokinetics in rats of CHMFL-KIT-110 solid dispersions

WU Yong; CHEN Dengjun; WANG Xiao; SUN Hongzhang; HUO Meirong

doi:10.11665/j.issn.1000-5048.20200607

Journal of China Pharmaceutical University > 2020 > 51(6): 688-695. > DOI: 10.11665/j.issn.1000-5048.20200607

WU Yong, CHEN Dengjun, WANG Xiao, SUN Hongzhang, HUO Meirong. Preparation，physicochemical properties and pharmacokinetics in rats of CHMFL-KIT-110 solid dispersions[J]. Journal of China Pharmaceutical University, 2020, 51(6): 688-695. DOI: 10.11665/j.issn.1000-5048.20200607

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Preparation，physicochemical properties and pharmacokinetics in rats of CHMFL-KIT-110 solid dispersions

Funds: This work was supported by the National Science and Technology Major Project-Major New Drug Creation (No.2017ZX09101001)

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Received Date: May 11, 2020
Revised Date: October 08, 2020

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Solid dispersions of the insoluble compound CHMFL-KIT-110 were prepared by solvent method with polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus),Poloxamer 407,PEG 6000,Copovidone (Kollidon VA64) as carriers and SLS,Tween 80,Cremophor RH40 as solubilizers. The optimal formulation was screened and obtained with dynamic solubilities and supersaturation performances as indexes. The final product was characterized by Fourier transform infrared (FT-IR),differential thermal analysis (DTA) and X-ray powder diffraction (XRPD). The stability and pharmacokinetic behavior in rats were also investigated. Results suggested that when the weight ratio of CHMFL-KIT-110/Soluplus/SLS was 1∶4∶0.5,dynamic solubility of the solid dispersions was significantly improved with no recrystallization. In the accelerated condition (40 °C,75% RH) for 30 days,CHMFL-KIT-110 in the solid dispersions was still amorphous with no crystal observed. The results of pharmacokinetics in rats showed that the c_max and AUC_0→_t of CHMFL-KIT-110 solid dispersions were 373.1 times and 358.7 times higher than those of free drugs,respectively. These results help to understand the formulation development and clinical practice of CHMFL-KIT-110.
- CHMFL-KIT-110,
- amorphous solid dispersions,
- Soluplus,
- solubility,
- bioavailability

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