Microcrystalline cellulose as an effective crystal growth inhibitor for the ternary Ibrutinib formulation. (1st February 2020)

• Record Type: Journal Article
• Authors: Zhang, Man; Suo, Zili; Peng, Xu; Gan, Na; Zhao, Ludan; Tang, Peixiao; Wei, Xin; Li, Hui
• Is Part Of: Carbohydrate polymers. Volume 229(2020)
• Publication Date: 2020-02-01
• Subjects: Ibrutinib (PubChem CID: 24821094) -- Microcrystalline cellulose (PubChem CID: 16211032) -- Oxalic acid ((PubChem CID: 971) -- Tartaric acid (PubChem CID: 875) -- Citric acid (PubChem CID: 311) -- Succinic acid (PubChem CID: 1110) -- Glutamic acid (PubChem CID: 33032) -- Arginine (PubChem CID: 6322) -- Histidine (PubChem CID: 6274) -- Glutamine (PubChem CID: 5961) -- Valine (PubChem CID: 6287) -- Tyrosine (PubChem CID: 6057) -- Alanine (PubChem CID: 5950); Co-amorphous -- Microcrystalline cellulose -- Ternary formulation -- Biosafety -- Bioavailability; Polysaccharides -- Periodicals; Polysaccharides -- Periodicals; Polysaccharides -- Périodiques; Electronic journals; 547.78
• DOI: 10.1016/j.carbpol.2019.115476
• Languages: English
• ISSNs: 0144-8617

Abstract

Graphical abstract: Highlights: Different IBR formulations were prepared by mechanochemical methods. MCC is an effective crystal growth inhibitor for the ternary IBR formulation. The biosafety of the ternary formulation was the same as that of IBR. The ternary IBR-OXA-MCC formulation enhances the oral bioavailability of IBR. Abstract: The objective of present study is to explore whether polysaccharide could be a crystal growth inhibitor in poorly soluble antitumor drug Ibrutinib (IBR) formulation. In this work, small molecular ligands (amino or organic acids) in co-amorphous system (CAS) were preliminarily screened. A polysaccharide, microcrystalline cellulose (MCC) was selected to stabilize amorphous drug and enhance pharmacokinetic properties. Fourier-transform infrared, Raman, and X-ray photoelectron spectroscopy confirmed the ionic interaction of the ternary IBR formulation. Moreover, the biosafety of the ternary formulation was the same as that of IBR while the in vitro performance advantage of the ternary formulation was converted into higher bioavailability in vivo experiments. Overall, MCC as an effective crystal growth inhibitor in the novel ternary IBR formulation is a promising approach to improve the dissolution rate of crystalline drugs and the stability of amorphous drugs, as well as providing a theoretical basis for clinical applications.