Design, development and evaluation of self-microemulsifying drug delivery system of pazopanib for enhanced dissolution rate and cytotoxic potential

Pazopanib is the first-line treatment for patients with advanced or metastatic renal cell carcinoma. However, the commercially available preparation is characterized by low solubility, poor bioavailability and suboptimal therapeutic concentrations in majority of patients. The aim of this study was to develop a Self-microemulsifying drug delivery system (SMEDDS) of pazopanib with improved solubility and faster dissolution rate in comparison to pure drug and marketed formulation. For the composition of SMEDDS, Capmul MCM C8, Tween 20 and propylene glycol were selected on the basis of solubility study. The ranges of oil, surfactant and co-solvent were selected by constructing a Pseudoternary phase diagram. The mixture design was used for optimizing the SMEDDS formulation.

Highlights

• Pazopanib dissolution rate can be appreciably improved through SMEDDS.
• The optimized pazopanib SMEDDS has a composition of Capmul MCM C8 (10%), Tween 20 (45%) and Propylene glycol (45%).
• The optimized SMEDDS released more than 80% of pazopanib within 5 min and showed globule of less than 500 nm.
• Pazopanib SMEDDS displayed a superior cytotoxic profile (2 to 3-fold higher) than Pazopanib API in ACHN cell.

The optimized pazopanib SMEDDS formulation consisting of Capmul MCM C8, Tween 20 and Propylene glycol at the levels of 10%, 45% and 45% respectively, showed smaller globule size (307.5 nm) and faster dissolution rate (more than 85% drug release in 5 min) as compared to the pure drug and marketed formulation. Additionally, the optimized SMEDDS was evaluated for percentage cytotoxicity in Human renal adenocarcinoma cell (ACHN) by MTT assay. The optimized SMEDDS showed 2–3 folds higher cytotoxicity in comparison to the pure drug in the ACHN cell line. These results indicate that pazopanib SMEDDS had improved solubility and dissolution rate compared to the pure drug and marketed formulation with enhanced cytotoxic potential.

Read more

Devender Kumar, Sushama Talegaonkar, Simrata Bedi, Kiran Dubey, Design, development and evaluation of self-microemulsifying drug delivery system of pazopanib for enhanced dissolution rate and cytotoxic potential, Journal of Drug Delivery Science and Technology, Volume 80, 2023, 104181, ISSN 1773-2247, https://doi.org/10.1016/j.jddst.2023.104181.

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