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Preparation and characterization of simvastatin/hydroxypropyl-beta-cyclodextrin inclusion complex using supercritical antisolvent (SAS) process.
Eur J Pharm Biopharm. 2007 Jun; 66(3):413-21.EJ

Abstract

In the present study, the practically insoluble drug, simvastatin (SV), and its inclusion complex with hydroxypropyl beta-cyclodextrin (HP-beta-CD) prepared using supercritical antisolvent (SAS) process were investigated to improve the aqueous solubility and the dissolution rate of drug, thus enhancing its bioavailability. Inclusion complexation in aqueous solution and solid state was evaluated by the phase solubility diagram, differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD), Fourier-transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The phase solubility diagram with HP-beta-CD was classified as A(L)-type at all temperatures investigated, indicating the formation of 1:1 stoichiometric inclusion complex. The apparent complexation constants (K(1:1)) calculated from phase solubility diagram were 774, 846 and 924 M(-1) at 25, 37 and 45+/-0.5 degrees C, respectively. No endothermic and characteristic diffraction peaks corresponding to SV was observed for the inclusion complex in DSC and PXRD. FT-IR study demonstrated the presence of intermolecular hydrogen bonds between SV and HP-beta-CD in inclusion complex, resulting in the formation of amorphous form. Aqueous solubility and dissolution studies indicated that the dissolution rates were remarkably increased in inclusion complex, compared with the physical mixture and drug alone. Moreover, SV/HP-beta-CD inclusion complex performed better than SV in reducing total cholesterol and triglyceride levels. This could be primarily attributed to the improved solubility and dissolution associated with inclusion complex between drug and HP-beta-CD. In conclusion, SAS process could be a useful method for the preparation of the inclusion complex of drug with HP-beta-CD and its solubility, dissolution rate and hypolipidemic activity were significantly increased by complexation between SV and HP-beta-CD.

Authors+Show Affiliations

College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17240129

Citation

Jun, Seoung Wook, et al. "Preparation and Characterization of Simvastatin/hydroxypropyl-beta-cyclodextrin Inclusion Complex Using Supercritical Antisolvent (SAS) Process." European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, vol. 66, no. 3, 2007, pp. 413-21.
Jun SW, Kim MS, Kim JS, et al. Preparation and characterization of simvastatin/hydroxypropyl-beta-cyclodextrin inclusion complex using supercritical antisolvent (SAS) process. Eur J Pharm Biopharm. 2007;66(3):413-21.
Jun, S. W., Kim, M. S., Kim, J. S., Park, H. J., Lee, S., Woo, J. S., & Hwang, S. J. (2007). Preparation and characterization of simvastatin/hydroxypropyl-beta-cyclodextrin inclusion complex using supercritical antisolvent (SAS) process. European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, 66(3), 413-21.
Jun SW, et al. Preparation and Characterization of Simvastatin/hydroxypropyl-beta-cyclodextrin Inclusion Complex Using Supercritical Antisolvent (SAS) Process. Eur J Pharm Biopharm. 2007;66(3):413-21. PubMed PMID: 17240129.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Preparation and characterization of simvastatin/hydroxypropyl-beta-cyclodextrin inclusion complex using supercritical antisolvent (SAS) process. AU - Jun,Seoung Wook, AU - Kim,Min-Soo, AU - Kim,Jeong-Soo, AU - Park,Hee Jun, AU - Lee,Sibeum, AU - Woo,Jong-Soo, AU - Hwang,Sung-Joo, Y1 - 2006/11/29/ PY - 2006/09/05/received PY - 2006/11/04/revised PY - 2006/11/22/accepted PY - 2007/1/24/pubmed PY - 2007/8/8/medline PY - 2007/1/24/entrez SP - 413 EP - 21 JF - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V JO - Eur J Pharm Biopharm VL - 66 IS - 3 N2 - In the present study, the practically insoluble drug, simvastatin (SV), and its inclusion complex with hydroxypropyl beta-cyclodextrin (HP-beta-CD) prepared using supercritical antisolvent (SAS) process were investigated to improve the aqueous solubility and the dissolution rate of drug, thus enhancing its bioavailability. Inclusion complexation in aqueous solution and solid state was evaluated by the phase solubility diagram, differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD), Fourier-transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The phase solubility diagram with HP-beta-CD was classified as A(L)-type at all temperatures investigated, indicating the formation of 1:1 stoichiometric inclusion complex. The apparent complexation constants (K(1:1)) calculated from phase solubility diagram were 774, 846 and 924 M(-1) at 25, 37 and 45+/-0.5 degrees C, respectively. No endothermic and characteristic diffraction peaks corresponding to SV was observed for the inclusion complex in DSC and PXRD. FT-IR study demonstrated the presence of intermolecular hydrogen bonds between SV and HP-beta-CD in inclusion complex, resulting in the formation of amorphous form. Aqueous solubility and dissolution studies indicated that the dissolution rates were remarkably increased in inclusion complex, compared with the physical mixture and drug alone. Moreover, SV/HP-beta-CD inclusion complex performed better than SV in reducing total cholesterol and triglyceride levels. This could be primarily attributed to the improved solubility and dissolution associated with inclusion complex between drug and HP-beta-CD. In conclusion, SAS process could be a useful method for the preparation of the inclusion complex of drug with HP-beta-CD and its solubility, dissolution rate and hypolipidemic activity were significantly increased by complexation between SV and HP-beta-CD. SN - 0939-6411 UR - https://www.unboundmedicine.com/medline/citation/17240129/Preparation_and_characterization_of_simvastatin/hydroxypropyl_beta_cyclodextrin_inclusion_complex_using_supercritical_antisolvent__SAS__process_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0939-6411(06)00336-5 DB - PRIME DP - Unbound Medicine ER -