The purpose of this study was to develop a combination method of wet milling and spray-drying technologies to prepare the solid dispersion and improve the dissolution rate of poorly water-soluble drug candidates. Azilsartan (AZL) was selected as the model drug for its poor water solubility. In the study, AZL-loaded solid dispersion was prepared with polyethylene glycol 6000 (PEG6000) and hydroxypropyl cellulose with super low viscosity (HPC-SL) as stabilizers by using combination of wet grinding and spray-drying methods. The high AZL loading solid dispersion was then characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR). Besides, dissolution test was carried out by the paddle method and stability investigation was also conducted. As a result, the dissolution rate of the solid dispersion tablets was found to be greater than conventional tablets, but in close agreement with market tablets. Furthermore, the formulation was shown to be stable at 40 ± 2°C and 75 ± 5% for at least 6 months, owing to its decreased particle size, morphology, and its crystal form. It was concluded that the combination of wet milling and spray-drying approaches to prepare solid dispersion would be a prospective method to improve the dissolution rate of poorly water-soluble drugs.
The study's aim is to develop and validate a rapid, selective and sensitive ultra-performance liquid chromatography-tandem mass spectrometry with multiple reaction monitoring (MRM) mode method for the simultaneous determination of entecavir and lamivudine in rat plasma.
A sensitive, selective and high-throughput UPLC-MS/MS method was developed and validated for the determination of a novel c-Met tyrosine kinase inhibitor, QBH-196, in rat plasma. QBH-196 and its analog BH357 (IS) were extracted from rat plasma using a mixture of dichloromethane and N-hexane (2:3, v/v). The chromatographic separation was carried out on Phenomenex C18 column (50 × 2.1 mm, 2.6 µm particle size) with a gradient mobile phase of methanol (A) and water containing 0.05% formic acid (B) at a flow rate of 0.2 mL/min. The assay was performed by positive electrospray ionization in multiple reaction monitoring mode using transitions of m/z 622.68 → 140.41 for QBH-196 and m/z 591.19 →126.21 for the IS, respectively. Good linearity was obtained over the concentration range of 8.0-4000 ng/mL (r(2) > 0.99) for QBH-196 and the lower limit of quantification was 8.0 ng/mL in rat plasma. Validations of the method, including its sensitivity, extraction recovery, matrix effect, intra- and inter-day precision, accuracy and stability, were all within acceptable limits. The established method was successfully applied to determine absolute oral bioavailability of QBH-196 in rats for the first time. The mean oral absolute bioavailability of QBH-196 was found to be about 40.8% and the elimination half-life was 40.0 ± 13.1 h. This result suggested that QBH-196 exhibits good oral absorption in vivo, which is very important for the further development of QBH-196 as a new oral anticancer drug.
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