ABSTRACT
Ibrutinib (IB) is the first Bruton s tyrosine kinase (BTK) inhibitor classified as BCS class-II, with multiple polymorphic forms. Development of its amorphous solid dispersion (ASD) is an effective approach to overcome drug's poor solubility and concerns regarding metastable polymorphic forms. In this work, Hot Melt Extrusion (HME) was used to develop robust ASD of ibrutinib and copovidone at different ratios. The ASDs were blended with a swellable crosslinked super-disintegrant and compressed into a sustained-release (SR) matrix. ASDs representing drug loadings of 20%, 40%, and 60% showed broad, amorphous "halos" and absence of an endotherm as revealed by X-ray powder diffraction (XRPD) and modulated differential scanning calorimetry (mDSC). Using dynamic oscillatory rheology, storage modulus, and viscosities versus temperature confirmed formation of a homogeneous dispersion with a manifestation of plasticizing effect of API. Micro-dissolution testing of ASDs in fasted state simulated intestinal fluid (FaSSIF) demonstrated >70% drug release compared to the saturation solubility of crystalline IB. Results of USP dissolution testing of SR tablets exhibited a desirable sustained delivery up to six hours with >88% drug release versus 34% release from tablets containing crystalline ibrutinib. Co-existence of ASD within the hydrating matrix provided unhindered drug release and release duration.