FIXED DOSE COMBINATION THERAPY OF IBRUTINIB AND QUERCETIN BY SNEDDS-DEVELOPMENT AND EVALUATION BY DESIGN OF EXPERIMENT

RASHMI BAGRI; RAVOURU NAGARAJU

doi:10.22159/ijap.2023v15i5.47820

Authors

RASHMI BAGRI Malla Reddy Pharmacy College, Maisammaguda, Secunderabad-500100, Telangana, India. Institute of Pharmaceutical Technology, Sri Padmavati Mahila Visvavidyalayam (Women’s University), Tirupati-517502, Andhra Pradesh, India https://orcid.org/0000-0002-9773-825X
RAVOURU NAGARAJU Institute of Pharmaceutical Technology, Sri Padmavati Mahila Visvavidyalayam (Women’s University), Tirupati-517502, Andhra Pradesh, India

DOI:

https://doi.org/10.22159/ijap.2023v15i5.47820

Keywords:

Ibrutinib, Quercetin, Box behnken design, Solubility, SNEDD

Abstract

Objective: Self-nano emulsifying drug delivery system (SNEDDS) comprising quercetin and ibrutinib as a fixed dosage combination therapy is being investigated to increase drug solubility and dissolution rate.

Methods: On the basis of preliminary solubility tests, castor oil, Kolliphor® RH 40, and PEG600 were utilised to construct ternary phase diagrams. The effect of the amount of Castor oil (A), Kolliphor® RH 40 (B), and PEG600 (C) on the particle size and encapsulation efficiency of ibrutinib and quercetin was evaluated and statistically analysed using multiple regression in 17 trials planned using a 33 Box-Behnken design. FTIR, XRD, DSC, SEM, and stability experiments were employed to characterise the optimised formulation. The particle size, zeta potential, polydispersity index, encapsulation efficiency, and in vitro drug release of ibrutinib and quercetin were also investigated.

Results: Ibrutinib and quercetin had encapsulation efficiencies of 61.56-87.22% (Y3) and 60.12-87.12%, respectively, according to the size range of SNEDDS formulations (1-17) of 70.18-200.56 nm. The optimised SNEDDS formulations (S1–S3) showed a particle size range of 71.12–76.38 nm, PDI of 0.126–0.312, zetapotential of-24.6–28.4, and encapsulation efficiencies of 88.98–90.22% and 84.96–86.78% for ibrutinib and quercetin, respectively. According to in vitro testing, the medication released from SNEDDS was released more quickly (>90% 600 min). The formulation was further evaluated using FTIR, XRD, DSC, SEM, and stability investigations, which validated the complexation of ibrutinib and quercetin in the drug's amorphous state and stability for six months.

Conclusion: This study revealed that SNEDDS could be used as a drug carrier for ibrutinib and quercetin due to their improved solubility and dissolution rate.

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