Formulation and Characterization of Nanoparticle Based Systems for Enhanced Oral Delivery of Acalabrutinib

Pharmaceutics

Acalabrutinib is an effective Bruton's tyrosine kinase inhibitor used in the management of B-cell malignancies; however, its clinical performance is hindered by poor aqueous solubility and low oral bioavailability. The present study was undertaken to formulate and characterize polymer–lipid hybrid nanoparticles (PLHNs) of acalabrutinib with the objective of improving its dissolution characteristics and oral delivery. Nanoparticles were prepared by the emulsification–solvent evaporation technique using mPEG-PCL copolymers of different molecular weights in combination with lipid components, followed by freeze-drying to obtain stable formulations. The prepared nanoparticles were evaluated for particle size, morphology, drug loading, thermal characteristics, and in vitro release behavior. The optimized formulations produced nanoparticles within the nanometer range and exhibited a narrow particle size distribution with spherical morphology. Drug encapsulation studies demonstrated efficient incorporation of acalabrutinib within the polymer–lipid matrix. Differential scanning calorimetry revealed the disappearance of the drug's characteristic melting endotherm, indicating successful conversion of the crystalline drug into an amorphous or molecularly dispersed state. Dissolution studies showed a significant improvement in drug release from the nanoparticle formulations compared with the pure drug. Among the developed systems, the formulation containing high-molecular-weight mPEG-PCL displayed superior release behavior, which may be attributed to its enhanced hydrophilic character and improved interaction with the dissolution medium. The findings suggest that polymer–lipid hybrid nanoparticles offer an efficient and promising approach for improving the dissolution properties and potential oral bioavailability of acalabrutinib.

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