Influence of the method of preparation on physicochemical characteristics of 1:1 simvastatin-β-cyclodextrin inclusion complex

Influence of the method of preparation on physicochemical characteristics of 1:1 simvastatin-β-cyclodextrin inclusion complex

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Title: Influence of the method of preparation on physicochemical characteristics of 1:1 simvastatin-β-cyclodextrin inclusion complex
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Article_Title: Influence of the method of preparation on physicochemical characteristics of 1:1 simvastatin-β-cyclodextrin inclusion complex
Authors: Emma Adriana Budura¹*, Dumitru Lupuleasa¹, Corina Aramă², Mihai Niţulescu³, Victoria Hîrjău¹
Affiliation: ¹ Pharmaceutical Technology Department, Faculty of Pharmacy, University of Medicine and Pharmacy „Carol Davila” Bucharest
² Analytical Chemistry Department, Faculty of Pharmacy, University of Medicine and Pharmacy „Carol Davila” Bucharest
³ Pharmaceutical Chemistry Department, Faculty of Pharmacy, University of Medicine and Pharmacy „Carol Davila” Bucharest
Abstract: The aim of the present study was to confirm the formation of 1:1 molar ratio inclusion complexes between the practically insoluble drug, simvastatin (SV) and beta-cyclodextrin (β-CD) in aqueous solution and in solid states by different techniques. Complexation in solution was evaluated using Higuchi-Connors phase solubility studies. Phase solubility diagram was classified as AL type, indicating the formation of 1:1 molar ratio inclusion complex, with an apparent stability constant (Kst) of 460 M-1. The inclusion complexes in solid state were prepared by co-precipitation and lyophilization techniques, and were subjected to physicochemical characterizations in comparison with the simple physical mixture prepared in the same 1:1 molar ratio. The complexes were evaluated by the scanning electron microscopy (SEM), powder X-ray diffraction, differential scanning calorimetry (DSC), and Fourier-transform infrared spectroscopy (FT-IR). All these studies showed the formation of 1:1 molar ratio inclusion complex between simvastatin and beta-cyclodextrin by both preparation methods used, but by liophilization the complexation proved to be complete.
Keywords: simvastatin, beta-cyclodextrin, inclusion complex, lyophilization, phase solubility diagrams
References: Seoung WJ, Min-Soo K, Jeong-Soo K, Hee Jun PA, Sibeum L, Jong-Soo W, Sung-Joo H, Preparation and charecterization of Simvastatin/hydroxylpropyl-β cyclodextrin inclusion complex using supercritical antisolvent (SAS) process, Eur. J. Pharm Biopharm, 66, 413-421, 2007.
Shiralashetti S.S., Patil A. S., Patil J. S., Influence of method of preparation on solubility, physicochemical properties and in vitro release profile of simvastatin cyclodextrin inclusion complexes: a comparative study, Int. J. of Curr. Pharm. Res, 2, 2, 7-12, 2010.
McClelland C. A., Stubbs R. J., Fix J. A., Pogany SA, Zentner G. M., Enhancement of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) reductase inhibitor efficacy through administration of a controlled-porosity osmotic pump dosage form, Pharm. Res., 8, 873-876, 1991.
Loftsson T., Brewster M., Pharmaceutical applications of cyclodextrins. 1. Drug solubilization and stabilization, J. Pharm. Sci., 85, 1017–1025, 1996.
Loftsson T., and Brewster M., Cyclodextrins as pharmaceutical solubilizers, Adv. Drug Deliver. Rev., 59, 645–666, 2007.
Higuchi T., Connors K.A., Phase-solubility techniques, Adv. Anal. Chem. Instrum., 4, 117–212, 1965.
Read_full_article: pdf/21-2011/21-3-2011/SU21-3-2011-Budura.pdf
Correspondence: Emma Adriana Budura, University of Medicine and Pharmacy „Carol Davila” Bucharest, Faculty of Pharmacy, Pharmaceutical Technology Department, No. 6 Traian Vuia St., 020956, Bucharest, Romania, Tel. +40-(21)- 3180740, email: emmacretu@aim.com

Read full article
Article Title: Influence of the method of preparation on physicochemical characteristics of 1:1 simvastatin-β-cyclodextrin inclusion complex
Authors: Emma Adriana Budura¹*, Dumitru Lupuleasa¹, Corina Aramă², Mihai Niţulescu³, Victoria Hîrjău¹
Affiliation: ¹ Pharmaceutical Technology Department, Faculty of Pharmacy, University of Medicine and Pharmacy „Carol Davila” Bucharest
² Analytical Chemistry Department, Faculty of Pharmacy, University of Medicine and Pharmacy „Carol Davila” Bucharest
³ Pharmaceutical Chemistry Department, Faculty of Pharmacy, University of Medicine and Pharmacy „Carol Davila” Bucharest
Abstract: The aim of the present study was to confirm the formation of 1:1 molar ratio inclusion complexes between the practically insoluble drug, simvastatin (SV) and beta-cyclodextrin (β-CD) in aqueous solution and in solid states by different techniques. Complexation in solution was evaluated using Higuchi-Connors phase solubility studies. Phase solubility diagram was classified as AL type, indicating the formation of 1:1 molar ratio inclusion complex, with an apparent stability constant (Kst) of 460 M-1. The inclusion complexes in solid state were prepared by co-precipitation and lyophilization techniques, and were subjected to physicochemical characterizations in comparison with the simple physical mixture prepared in the same 1:1 molar ratio. The complexes were evaluated by the scanning electron microscopy (SEM), powder X-ray diffraction, differential scanning calorimetry (DSC), and Fourier-transform infrared spectroscopy (FT-IR). All these studies showed the formation of 1:1 molar ratio inclusion complex between simvastatin and beta-cyclodextrin by both preparation methods used, but by liophilization the complexation proved to be complete.
Keywords: simvastatin, beta-cyclodextrin, inclusion complex, lyophilization, phase solubility diagrams
References: Seoung WJ, Min-Soo K, Jeong-Soo K, Hee Jun PA, Sibeum L, Jong-Soo W, Sung-Joo H, Preparation and charecterization of Simvastatin/hydroxylpropyl-β cyclodextrin inclusion complex using supercritical antisolvent (SAS) process, Eur. J. Pharm Biopharm, 66, 413-421, 2007.
Shiralashetti S.S., Patil A. S., Patil J. S., Influence of method of preparation on solubility, physicochemical properties and in vitro release profile of simvastatin cyclodextrin inclusion complexes: a comparative study, Int. J. of Curr. Pharm. Res, 2, 2, 7-12, 2010.
McClelland C. A., Stubbs R. J., Fix J. A., Pogany SA, Zentner G. M., Enhancement of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) reductase inhibitor efficacy through administration of a controlled-porosity osmotic pump dosage form, Pharm. Res., 8, 873-876, 1991.
Loftsson T., Brewster M., Pharmaceutical applications of cyclodextrins. 1. Drug solubilization and stabilization, J. Pharm. Sci., 85, 1017–1025, 1996.
Loftsson T., and Brewster M., Cyclodextrins as pharmaceutical solubilizers, Adv. Drug Deliver. Rev., 59, 645–666, 2007.
Higuchi T., Connors K.A., Phase-solubility techniques, Adv. Anal. Chem. Instrum., 4, 117–212, 1965.
*Correspondence: Emma Adriana Budura, University of Medicine and Pharmacy „Carol Davila” Bucharest, Faculty of Pharmacy, Pharmaceutical Technology Department, No. 6 Traian Vuia St., 020956, Bucharest, Romania, Tel. +40-(21)- 3180740, email: emmacretu@aim.com