Ibrutinib is the first Bruton`s tyrosine kinase (BTK) inhibitor for oral administration approved by FDA in 2014. It is the first-line treatment for B-cell malignancies, which are the most common hematologic neoplasia. Ibrutinib is a relatively safe alternative for currently used treatment modalities that are associated with long-term toxicity and resistance. However, ibrutinib is considered as BCS class II drug and has very low solubility in an aqueous medium (13 μg/ml at PH 8.0) and has six different polymorphic forms. Furthermore, recommended daily dose of ibrutinib is about 420 mg to 560 mg, which causes severe GI disturbances, with poor patient compliance. This represent a major critical concern because drug is used chronically. Increasing drug solubility and controlling rate of drug release may improve both bioavailability at significantly lower daily administered doses and by implication could minimize GI side effects and improve patient compliance.The objective of this study is to utilize Hot Melt Extrusion (HME) to develop a stable amorphous solid dispersion (ASD) of ibrutinib using Copovidone (PlasdoneTM S-630 Ultra) as a carrier for inclusion into a hydrating matrix for sustained release delivery. Development of ASD based on HME is an efficient method to overcome poor solubility problem and stabilize the drug`s metastable polymorphic states. It is known that amorphous systems are energetically at a higher thermodynamic state and can dissolve to a much greater extent relative to their crystalline counterpart. A stable sustained-release ASD based system may offer many advantages, including reduction in frequency of administration and GI disturbances with propensity to enhance solubilization while suppressing recrystallization. The ASD systems prepared in this study was stable, amorphous, and single-phase systems up to 60% API load as confirmed by X-ray powder diffraction (XRPD), modulated differential scanning calorimetry (mDSC), and rheological analysis. Supersaturated micro-dissolution testing of melt-extruded powder in fasted state simulated intestinal fluid demonstrated up to 70% increase in supersaturation solubility than the saturation solubility of crystalline counterparts. In addition, dissolution data based on the standard USP paddle method for the formulated SR tablets demonstrated a prolonged release up to six hours and a maximum of 53% higher drug release than crystalline ibrutinib. In conclusion, the results of this study indicate that ibrutinib amorphous solid dispersion developed utilizing hot-melt extrusion technology and Copovidone (PlasdoneTM S-630 Ultra) as a carrier is able to produce stable and homogeneous single-phase ASD system with enhanced solubility and desirable sustained drug release rate. / Pharmaceutical Sciences