Merck
  • Home
  • Search Results
  • Microenvironmental pH-modified solid dispersions to enhance the dissolution and bioavailability of poorly water-soluble weakly basic GT0918, a developing anti-prostate cancer drug: preparation, characterization and evaluation in vivo.

Microenvironmental pH-modified solid dispersions to enhance the dissolution and bioavailability of poorly water-soluble weakly basic GT0918, a developing anti-prostate cancer drug: preparation, characterization and evaluation in vivo.

International journal of pharmaceutics (2014-08-31)
Meiyan Yang, Shaolong He, Yunzhou Fan, Yuli Wang, Zhenzhong Ge, Li Shan, Wei Gong, Xiaoli Huang, Youzhi Tong, Chunsheng Gao
ABSTRACT

The aim of the present work was to design a pH-modified solid dispersion (pH(M)-SD) that can improve the dissolution and bioavailability of poorly water-soluble weakly basic GT0918, a developing anti-prostate cancer drug. To select the appropriate acidifiers, a solubility test was carried out first. Solid dispersions (SDs) containing GT0918 and polyvinylpyrrolidone (PVP) were prepared using a solvent evaporation method and were characterized using dissolution studies in different media. The solid states of the SDs were investigated using scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and Fourier transformed infrared spectroscopy (FTIR). The in vivo pharmacokinetics of the pH(M)-SDs tablets were also studied in beagle dogs compared to the conventional tablets. The optimized pH(M)-SD (GT0918/PVP/citric acid, 1:2:2 weight ratio) exhibited a significant improvement in the dissolution behavior compared to both the physical mixture and the binary SDs. Solid-state characterization revealed that the amorphous formation of GT0918 in the SDs and the strong H-bonding were only found in the pH(M)-SDs containing citric acid. Furthermore, the GT0918-loaded pH(M)-SD tablets showed a higher AUC and a lower tmax compared to the conventional tablets. Accordingly, the pH(M)-SD might be an efficient route for enhancing the dissolution and bioavailability of poorly water-soluble GT0918.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Succinic acid, BioReagent, BioRenewable, suitable for cell culture, suitable for insect cell culture
Sigma-Aldrich
Succinic acid, BioXtra, BioRenewable, ≥99.0%
Sigma-Aldrich
Succinic acid, ReagentPlus®, BioRenewable, ≥99.0%
Sigma-Aldrich
Citric acid, BioUltra, anhydrous, ≥99.5% (T)
Sigma-Aldrich
Fumaric acid, tested according to USP/NF
Supelco
Citric acid, Anhydrous, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Citric acid, anhydrous, suitable for cell culture, suitable for plant cell culture
Sigma-Aldrich
Citric acid, 99%
Sigma-Aldrich
2-Hydroxybutyric acid sodium salt, 97%
Sigma-Aldrich
Succinic acid, ACS reagent, ≥99.0%
Sigma-Aldrich
Fumaric acid, FCC, FG
Sigma-Aldrich
Citric acid, ≥99.5%, FCC, FG
Sigma-Aldrich
Succinic acid, purum p.a., ≥99.0% (T)
Sigma-Aldrich
Succinic acid, puriss. p.a., ACS reagent, ≥99.5% (T)
Sigma-Aldrich
Fumaric acid, ≥99.0% (T)
Sigma-Aldrich
Lactose, tested according to Ph. Eur.
Sigma-Aldrich
Citric acid, ACS reagent, ≥99.5%
Supelco
Fumaric Acid, Pharmaceutical Secondary Standard; Certified Reference Material
SAFC
Fumaric acid
Sigma-Aldrich
Citric acid, Vetec, reagent grade, 99%
Sigma-Aldrich
Fumaric acid, Vetec, reagent grade, 99%
Sigma-Aldrich
Succinic acid, Vetec, reagent grade, 98%
USP
Citric acid, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Citric acid, anhydrous, free-flowing, Redi-Dri, ACS reagent, ≥99.5%
Supelco
Succinic Acid, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
Citric acid, meets analytical specification of Ph. Eur., BP, USP, E330, anhydrous, 99.5-100.5% (based on anhydrous substance)
Fumaric acid, European Pharmacopoeia (EP) Reference Standard
Citric acid, anhydrous, European Pharmacopoeia (EP) Reference Standard
Supelco
Fumaric acid, certified reference material, TraceCERT®
Supelco
Citric acid, certified reference material, TraceCERT®