Solubility Enhancement of Sunitinib Using PVP K-30 and Urea-Based Solid Dispersions: Comparative Formulation and Kinetic Evaluation
Keywords:
Solubility Enrichment, Solubility Enrichment, Sunitinib, Sunitinib, PVP K-30, PVP K-30, Solid Dispersion, Solid Dispersion, Urea, Urea, Bioavailability, BioavailabilityAbstract
Sunitinib is a poorly water-soluble, multi-targeted receptor tyrosine kinase (RTK) inhibitor used in the treatment of renal cell carcinoma (RCC) and gastrointestinal stromal tumours (GIST). Enhancing its solubility and dissolution is crucial for improving bioavailability. This study explores the solid dispersion technique as an effective approach for solubility enhancement. Solid dispersions of Sunitinib were prepared using the solvent evaporation method with hydrophilic carriers PVP K-30 and urea in different drug-to-carrier ratios. The formulations were evaluated through solubility studies, in vitro dissolution, and drug release kinetics. UV spectrophotometric analysis showed maximum absorbance at 457 nm, confirming suitability for quantitative determination. Among the formulations, the dispersion containing Sunitinib and urea in a 1:2 ratio F4 exhibited the highest drug release (249.38 µg/ml in 90 minutes), with the drug release following first-order kinetics. From the observation, urea proved more convenient for enhancing the solubility of Sunitinib. The results indicate that solid dispersion with appropriate carriers significantly improves dissolution behaviour. This study confirms that solid dispersion is a promising strategy to improve the aqueous solubility of hydrophobic drugs like Sunitinib, thereby enhancing their therapeutic efficacy and bioavailability.
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Kumar R, Singh A, Salwan R, Bhanot R, Rahar S and Dhawan RK,GSC(2023)Biological and pharmaceutical sciences,22(01),114-121.
Amidon GL, Lennernas H, Shah VP and Crison JR (1995). Theoretical basis for a biopharmaceutical drug classification: the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res., 12(3): 413-420.
Savjani K, Gajjar A, Savjani J.(2012) Drug solubility: Importance and enhancement Technique. ISRNP. 1-10.
Lobenberg R, Amidon GL.(2000) Modern bioavailability, bioequivalence and biopharmaceutical classification system. New scientific approaches to international regulatory standards. Eur J Pharm Sci. 50(1):3–20.
Singh et al,(2011) A review on solid dispersion, IJPLS, 2(9), 1078-1095.
Chaudhary A, Nagaich U, Gulati N, et al.(2012) Enhancement of solubilization and bioavailability of poorly soluble drugs by physical and chemical modifications. J Adv Pharm Technol Res. 2(1):32–67.
Dixit AK., Singh RP,(2012) solid dispersion – A strategy for improving the solubility of poorly soluble drugs, IJRPBS, 3(2), 960-966.
Blagden N, Gavan P, York P. Crystal(2007) engineering of active pharmaceutical ingredients to improve solubility and dissolution rates. Adv Drug Del Rev. 59(30):617–630.
Dhirendra K, Lewis S, Udupa N, et al.(2009) Solid Dispersions: A Review. Pak J Pharm Sci., 22(2):234–246.
International Conference on Harmonization of Technical Requirements for Registration of Pharmaceutical for Human Use ICH Guideline:(1994) Validation of Analytical procedures text and methodology Q2(R1);
Edwin P Rock, Vicki goodman, Janet X Jiang, KoorosMahjoob, S Leigh Verbois, David Morse, et al.(2007) Food and drug administration drug approval summary: sunitinib m. for the treatment of gastrointestinal stromal tumor and advanced renal cell carcinoma. Oncologist;12:107-13.
Val R Adams, Markos Leggas.(2007) Sunitinib m. for the treatment of metastatic renal cell carcinoma and gastrointestinal stromal tumors. Clin Ther;29:1338-53.
Sandhya B, Chinnari Harika V, Bikshal Babu Kasimalla, Reshma Syed, Kalpana Pammi.(2011) RP-HPLC method development and validation for the analysis of Sunitinib in pharmaceutical dosage forms. Int J Sci Innovations Discoveries;1:441-50.
De Bruijn P, Sleijfer S, Lam MH, Mathijssen RH, Wiemer EA, Loos WJ. (2010) Bioanalytical method for the quantification of Sunitinib and its n-desethyl metabolite SU12662 in human plasma by Ultra performance liquid chromatography/tandem triple quadrupole Mass spectrometry. J Pharm Biomed Anal;51:934-41.
Marie Christine Etienne-Grimaldi, Nicole Renée, Hassan Izzedine, Gérard Milano.(2009) A routine feasible HPLC analysis for the anti- angiogenic tyrosine kinase inhibitor, Sunitinib, and its main metabolite, SU12662, in plasma. J Chromatogr;877:3757-61.
Benoit Blanchet, Carole Saboureau, Anne-Sophie Benichou, Bertrand Billemont, Fabrice Taieb, Stanislas Ropert, et al.(2009) Development and validation of an HPLC-UV-visible method for sunitinib quantification in human plasma. Clin Chim Acta ;404:134-9.
Hsu CH, Cui Z, Mumper RJ, et al.(2023) Micellar Solubilization of Some Poorly Soluble Antidiabetic Drugs. AAPS Pharm Sci Tech. , 9(2):431–436.
Huang Y, Dai WG.(2014) Fundamental aspects of solid dispersion technology for poorly soluble drugs. Acta Pharm Sin B. 4(1):18–25.
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