QUALITY BY DESIGN ASSOCIATED IBRUTINIB LOADED NANOSUSPENSION FOR AMELIORATED DISSOLUTION USING NANO BALL MILLING AND SPRAY DRYING METHODS

VALLABH DEULKAR; RAGHUVEER  PATHURI

doi:10.22159/ijap.2025v17i4.54129

Authors

VALLABH DEULKAR Department of Pharmaceutics, GITAM School of Pharmacy, Hyderabad Campus, GITAM (Deemed to be University), India
RAGHUVEER PATHURI Department of Pharmaceutics, GITAM School of Pharmacy, Hyderabad Campus, GITAM (Deemed to be University), India https://orcid.org/0000-0001-5918-1393

DOI:

https://doi.org/10.22159/ijap.2025v17i4.54129

Keywords:

Hypromellose, Ibrutinib, Fast fed variability, Nanosuspension, Nano-Ball mill, Sodium lauryl sulfate

Abstract

Objective: The aim of the present work was to enhance the solubility, reduce fast-fed variability, and increase the oral bioavailability of Ibrutinib (IBR), a Biopharmaceutical Classification System (BCS) class II drug, through the development of a Nanosuspension (NS) formulation.

Methods: Ibrutinib Nanosuspension (IBR NS) was formulated using a three-factor, three-level Box-Behnken Design (BBD). The NS was prepared using a nano ball mill followed by spray drying, with Hypromellose and sodium lauryl sulfate as stabilizers. The particle size and Polydispersity Index (PDI) were measured, and the role of Vitamin E D-α-Tocopheryl Polyethylene Glycol 1000 Succinate (TPGS) as a stabilizer was evaluated. The formulation was characterized using Scanning Electron Microscopy (SEM), X-Ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FTIR), and Differential Scanning Calorimetry (DSC). Stability studies were conducted over a 90-day storage period.

Results: The particle size of the NS after nano ball milling ranged from 294.53 to 408.83 nm, with PDI values between 0.075 and 0.278. After spray drying with Vitamin E TPGS, the particle size was further reduced to 135.6 nm. SEM images confirmed the presence of distinct spherical nanoparticles. XRD, FTIR, and DSC studies demonstrated excellent compatibility between the drug and the stabilizers. The formulation remained stable over 90 days of storage. The solubility of IBR NS increased by 12.96-fold compared to the plain drug. In dissolution medium,>94% drug release was achieved within 2 h compared to 63% for plain IBR. Structural characterization confirmed amorphization and compatibility.

Conclusion: The developed IBR NS significantly enhanced solubility, reduced fast-fed variability, and improved oral bioavailability. The use of Hypromellose, sodium lauryl sulfate, and Vitamin E TPGS as stabilizers proved effective in achieving a stable and optimized formulation. This approach holds promise for improving the delivery of poorly soluble drugs like IBR.

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