Liquid antisolvent precipitation process for solubility modulation of bicalutamide

Meer, Tarique; Sawant, Kiran; Amin, Purnima

doi:10.2478/v10007-011-0036-0

Abstract

Liquid antisolvent process was explored as a solubility modulating tool. Bicalutamide, a poorly water soluble drug, was used as a candidate. Low aqueous solubility and poor dissolution of bicalutamide results into poor and variable bioavailability. Therefore, the objective of the present work was to modify the solubility of bicalutamide using the liquid antisolvent precipitation process. HPMC E5 and Poloxamer 407 were shortlisted as a hydrophilic polymer and surfactant, respectively, for the process. Process optimization was done with respect to the hydrophilic polymer, surfactant and drug loading concentration. The resultant microcrystals were characterized with various instrumental techniques for material characterization such as IR, DSC, SEM, XRD, particle size, specific surface area and dissolution kinetics.

References

D. R. Vega, G. Polla, A. Martinez, E. Mendioroz and M. Reionoso, Conformational polymorphism in bicalutamide, Int. J. Pharm. 328 (2007) 112-118; DOI: 10.1016/j.ijpharm.2006.08.001.10.1016/j.ijpharm.2006.08.00116978811
Search in Google Scholar
D. Wu, J. Yang, V. A. Nair, D. D. Miller and J. T. Dalton, Pharmacokinetics and metabolism of a selective androgen receptor modulator in rats: implication of molecular properties and intensive metabolic profile to investigate ideal pharmacokinetic chrecteristics of a propanamide in preclinical study, Drug Metab. Dispos. 34 (2006) 483-494; DOI: 10.1124/dmd.105.006643.10.1124/dmd.105.006643203987716381665
Search in Google Scholar
Y. Le, H. Ji, J. F. Chen, Z. Shen, J. Yun and M. Pu, Nanosized bicalutamide and its molecular structure in solvents, Int. J. Pharm. 370 (2009) 175-180; DOI: 10.1016/j.ijpharm.2008.11.025.10.1016/j.ijpharm.2008.11.02519101616
Search in Google Scholar
A. Abdalla and K. Mäder, Preparation and characterization of a self-emulsifying pellet formulation, Eur. J. Pharm. Biopharm. 66 (2007) 220-226; DOI: 10.1016/j.ejpb.2006.11.015.10.1016/j.ejpb.2006.11.01517196807
Search in Google Scholar
I. Kanfer, Report on the international workshop on the biopharmaceutics classification system (BCS): scientific and regulatory aspects in practice, J. Pharm. Pharm. Sci. 5 (2000) 1-4.
Search in Google Scholar
P. Kocbek, S. Baumgartner and J. Kristl, Preparation and evaluation of nanosuspensions for enhancing the dissolution of poorly soluble drugs, Int. J. Pharm. 312 (2006) 179-186; DOI: 10.1016/j.ijpharm.2006.01.008.10.1016/j.ijpharm.2006.01.00816469459
Search in Google Scholar
Y. Dong, W. N. Kiong, S. Shen, S. Kim and R. B. H. Tan, Preparation and characterization of spironolactone nanoparticles by antisolvent precipitation, Int. J. Pharm. 375 (2009) 84-88; DOI: 10.1016/j.ijpharm.2009.03.013.10.1016/j.ijpharm.2009.03.01319481693
Search in Google Scholar
A. Balakrishnan, B. D. Rege, G. L. Amidon and J. E. Polli, Surfactant-mediated dissolution: contributions of solubility enhancement and relatively low micelle diffusivity, J. Pharm. Sci. 93 (2004) 2064-2075; DOI: 10.1002/jps.20118.10.1002/jps.2011815236455
Search in Google Scholar
G. S. Jadhav and P. R. Vavia, Physicochemical in silico and in-vivo evaluation of danazole-β-cyclodextrin complex, Int. J. Pharm. 352 (2008) 5-16 DOI: 10.1016/j.ijpharm.2007.10.005.10.1016/j.ijpharm.2007.10.00518023545
Search in Google Scholar
I. Ilić, R. Dreu, M. Burjak, M. Homar, J. Kerč and J. S. Srčič, Microparticle size control and glimepiride microencapsulation using spray congealing technology, Int. J. Pharm. 381 (2009) 176-183; DOI: 10.1016/j.ijpharm.2009.05.011.10.1016/j.ijpharm.2009.05.01119446625
Search in Google Scholar
M. D. Moore and P. L. D. Wildfong, Aqueous solubility enhancement through engineering of binary solid composites: pharmaceutical applications, J. Pharm. Innov. 4 (2009) 36-49; DOI: 10.1007/s12247-009-9053-7.10.1007/s12247-009-9053-7
Search in Google Scholar
P. Zhang, H. Ye, T. Min and C. Zhang, Water soluble poly(ethylene glycol) prodrug of silybin: design, synthesis, and characterization, J. Appl. Polym. Sci. 107 (2008) 3230-3235; DOI: 10.1002/app.27450.10.1002/app.27450
Search in Google Scholar
Y. Le, H. Ji, J. Chen, Z. Shen, J. Yun and M. Pu, Nanosized bicalutamide and its molecular structure in solvents, Int. J. Pharm. 370 (2009) 175-180 DOI: 10.1016/j.ijpharm.2008.11.025.10.1016/j.ijpharm.2008.11.02519101616
Search in Google Scholar
R. P. Bagwe and K. C. Khilar, Effects of the intermicellar exchange rate and cations on the size of silver chloride nanoparticles formed in reverse micelles of AOT, Langmuir 13 (1997) 6432-6438; DOI: 10.1021/la980248q.10.1021/la980248q
Search in Google Scholar
J. Y. Zhang, Z. G. Shen, J. Zhong, T. T. Hu, J. F. Chen, Z. Q. Ma and J. Yun, Preparation of amorphous cefuroxime axetil nanoparticles by controlled nanoprecipitation method without surfactants, Int. J. Pharm. 323 (2006) 153-160; DOI: 10.1016/i.ijpharm.2006.05.048.
Search in Google Scholar
U. S. Food and Drug Administration, Dissolution Methods, Bicalutamide, FDA, Silver Sping (MD), Dec 15 2005; http://www.accessdata.fda.(MD)gov/scripts/cder/dissolution/dsp_Search-Results_Dissolutions.cfm?PrintAll=1
Search in Google Scholar

Liquid antisolvent precipitation process for solubility modulation of bicalutamide

Abstract

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