生物利用度
溶解度
化学
伊布替尼
药理学
药品
药代动力学
差示扫描量热法
材料科学
有机化学
医学
白血病
物理
慢性淋巴细胞白血病
内科学
热力学
作者
Divya Dhatri Kara,Pragathi Devanand Bangera,Chetan Hasmukh Mehta,Katikala Tanvi,Mahalaxmi Rathnanand
出处
期刊:Aaps Pharmscitech
[Springer Nature]
日期:2023-08-08
卷期号:24 (6)
被引量:2
标识
DOI:10.1208/s12249-023-02621-9
摘要
Ibrutinib (IBR) is a biopharmaceutical classification system (BCS) class II drug and an irreversible Bruton's tyrosine kinase (BTK) inhibitor. IBR has an extremely low oral bioavailability due to the activity of the CYP3A4 enzyme. The current intention of the research was to enhance solubility followed by oral bioavailability of IBR using the hot melt extrusion (HME) technique by formulating drug-drug cocrystals (DDCs). Ketoconazole (KET) is an active CYP3A4 inhibitor and was selected based on computational studies and solubility parameter prediction. Differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), powder X-ray diffraction (PXRD), thermogravimetric analysis (TGA), proton nuclear magnetic resonance (1H NMR), and scanning electron microscopy (SEM) evaluations were employed for estimating the formation of IBR-KET DDCs. The IBR-KET DDC system was discovered to have a hydrogen bond (H-bond) and π-π-stacking interactions, in accordance with the computational results. Further, IBR-KET DDCs showed enhanced solubility, stability, powder dissolution, in vitro release, and flow properties. Furthermore, IBR-KET-DDCs were associated with enhanced cytotoxic activity in K562-CCL-243 cancer cell lines when compared with IBR and KET alone. In vivo pharmacokinetic studies have shown an enhanced oral bioavailability of up to 4.30 folds of IBR and 2.31 folds of KET through IBR-KET-DDCs compared to that of the IBR and KET suspension alone. Thus, the prepared IBR-KET-DDCs using the HME technique stand as a favorable drug delivery system that augments the solubility and oral bioavailability of IBR along with KET.
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