EMAIL THIS PAGE TO A FRIEND

International journal of pharmaceutics

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.


PMID 25171976

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.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

ARK2164
Fumaric acid, PharmaGrade, USP/NF, Manufactured under appropriate GMP controls for pharma or biopharmaceutical production.
C4H4O4
F8509
Fumaric acid, BioReagent, suitable for cell culture
C4H4O4
47910
Fumaric acid, ≥99.0% (T)
C4H4O4
03761
Fumaric acid, tested according to USP/NF
C4H4O4
F0600000
Fumaric acid, European Pharmacopoeia (EP) Reference Standard
C4H4O4
76635
Fumaric acid, certified reference material, TraceCERT®
C4H4O4
F19353
Fumaric acid, 99%
C4H4O4
W248800
Fumaric acid, ≥99%, FCC, FG
C4H4O4
PHR1270
Fumaric Acid, Pharmaceutical Secondary Standard; Certified Reference Material
C4H4O4
S3674
Succinic acid, BioXtra, ≥99.0%
C4H6O4
69612
Succinic acid, matrix substance for MALDI-MS, ≥99.5% (T), Ultra pure
C4H6O4
S9512
Succinic acid, BioReagent, suitable for cell culture, suitable for insect cell culture
C4H6O4
398055
Succinic acid, ACS reagent, ≥99.0%
C4H6O4
S7501
Succinic acid, ReagentPlus®, ≥99.0%
C4H6O4
49893
Succinic acid, certified reference material, TraceCERT®
C4H6O4
14079
Succinic acid, puriss. p.a., ACS reagent, ≥99.5% (T)
C4H6O4
14080
Succinic acid, purum p.a., ≥99.0% (T)
C4H6O4
W502707
Succinic acid, FCC
C4H6O4
W502715
Succinic acid, natural
C4H6O4
PHR1418
Succinic Acid, Pharmaceutical Secondary Standard; Certified Reference Material
C4H6O4