Solubility and bioavailability improvement of pazopanib hydrochloride.
Int J Pharm
; 544(1): 181-190, 2018 Jun 10.
Article
em En
| MEDLINE
| ID: mdl-29680279
ABSTRACT
The anti-cancer drug pazopanib hydrochloride (PZH) has a very low aqueous solubility and a variable oral bioavailability. A new pharmaceutical formulation with an improved solubility may enhance the bioavailability and reduce the variability. A broad selection of polymer excipients was tested for their compatibility and solubilizing properties by conventional microscopic, thermal and spectrometric techniques. A wet milling and mixing technique was used to produce homogenous powder mixtures. The dissolution properties of the formulation were tested by a pH-switch dissolution model. The final formulation was tested in vivo in cancer patient following a dose escalation design. Of the tested mixture formulations, the one containing the co-block polymer Soluplus® in a 81 ratio with PZH performed best in terms of in vitro dissolution properties. The in vivo results indicated that 300â¯mg of the developed formulation yields similar exposure and a lower variability (379⯵g/mL∗h (36.7% CV)) than previously reported values for the standard PZH formulation (Votrient®) at the approved dose of 800â¯mg. Furthermore, the expected plasma-Cthrough levels (27.2⯵g/mL) exceeds the defined therapeutic efficacy threshold of 20⯵g/mL.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pirimidinas
/
Sulfonamidas
/
Inibidores da Angiogênese
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article