Design and optimization of self-nanoemulsifying drug delivery systems (SNEDDS) for enhanced dissolution of gemfibrozil

被引:118
作者
Sierra Villar, Ana Maria [2 ]
Clares Naveros, Beatriz [1 ]
Calpena Campmany, Ana Cristina [3 ]
Aroztegui Trenchs, Monserrat [2 ]
Barbe Rocabert, Coloma [2 ]
Halbaut Bellowa, Lyda [2 ]
机构
[1] Univ Granada, Pharm & Pharmaceut Technol Dept, Fac Pharm, E-18071 Granada, Spain
[2] Univ Barcelona, Pharm & Pharmaceut Technol Dept, Fac Pharm, E-08028 Barcelona, Spain
[3] Univ Barcelona, Biopharm & Pharmacokinet Unit, Fac Pharm, E-08028 Barcelona, Spain
关键词
Gemfibrozil; Self-nanoemulsifying drug delivery systems; SNEDDS; Pseudoternary phase diagrams; Box-Behnken design; IN-VITRO CHARACTERIZATION; NECROSIS-FACTOR-ALPHA; ORAL DELIVERY; SOLUBLE DRUGS; RELEASE; FORMULATION; ABSORPTION; BIOAVAILABILITY; HYDROCHLORIDE; CYCLOSPORINE;
D O I
10.1016/j.ijpharm.2012.04.001
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Self-nanoemulsifying drug delivery systems of gemfibrozil were developed under Quality by Design approach for improvement of dissolution and oral absorption. Preliminary screening was performed to select proper components combination. Box-Behnken experimental design was employed as statistical tool to optimize the formulation variables, X-1 (Cremophor (R) EL), X-2 (Capmul (R) MCM-C8), and X-3 (lemon essential oil). Systems were assessed for visual characteristics (emulsification efficacy), turbidity, droplet size, polydispersity index and drug release. Different pH media were also assayed for optimization. Following optimization, the values of formulation components (X-1, X-2, and X-3) were 32.43%, 29.73% and 21.62%, respectively (16.22% of gemfibrozil). Transmission electron microscopy demonstrated spherical droplet morphology. SNEEDS release study was compared to commercial tablets. Optimized SNEDDS formulation of gemfibrozil showed a significant increase in dissolution rate compared to conventional tablets. Both formulations followed Weibull mathematical model release with a significant difference in t(d) parameter in favor of the SNEDDS. Equally amodelistic parameters were calculated being the dissolution efficiency significantly higher for SNEDDS, confirming that the developed SNEDDS formulation was superior to commercial formulation with respect to in vitro dissolution profile. This paper provides an overview of the SNEDDS of the gemfibrozil as a promising alternative to improve oral absorption. (C) 2012 Elsevier B.V. All rights reserved.
引用
收藏
页码:161 / 175
页数:15
相关论文
共 68 条
[1]   A new self-emulsifying drug delivery system (SEDDS) for poorly soluble drugs: Characterization, dissolution, in vitro digestion and incorporation into solid pellets [J].
Abdalla, Ahmed ;
Klein, Sandra ;
Maedder, Karsten .
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 2008, 35 (05) :457-464
[2]   DSC, X-ray and FTIR studies of a gemfibrozil/dimethyl-β-cyclodextrin inclusion complex produced by co-grinding [J].
Aigner, Z. ;
Berkesi, O. ;
Farkas, G. ;
Szabo-Revesz, P. .
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, 2012, 57 :62-67
[3]   The use of solid self-emulsifying systems in the delivery of diclofenac [J].
Attama, AA ;
Nzekwe, IT ;
Nnamani, PO ;
Adikwu, MU ;
Onugu, CO .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2003, 262 (1-2) :23-28
[4]   SNEDDS containing bioenhancers for improvement of dissolution and oral absorption of lacidipine. I: Development and optimization [J].
Basalious, Emad B. ;
Shawky, Nevine ;
Badr-Eldin, Shaimaa M. .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2010, 391 (1-2) :203-211
[5]  
Birdi K.S., 2009, HDB SURFACE COLLOID
[6]  
Broijersen A, 1996, THROMB HAEMOSTASIS, V76, P171
[7]   Lipid excipients and delivery systems for pharmaceutical development: A regulatory perspective [J].
Chen, Mei-Ling .
ADVANCED DRUG DELIVERY REVIEWS, 2008, 60 (06) :768-777
[8]   Solid solubility of antilipemic agents and micronization of gemfibrozil in supercritical carbon dioxide [J].
Chen, Yen-Ming ;
Lin, Pai-Ching ;
Tang, Muoi ;
Chen, Yan-Ping .
JOURNAL OF SUPERCRITICAL FLUIDS, 2010, 52 (02) :175-182
[9]   Formulation and physical characterization of water-in-oil microemulsions containing long- versus medium-chain glycerides [J].
Constantinides, PP ;
Scalart, JP .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 1997, 158 (01) :57-68
[10]   Modeling and comparison of dissolution profiles [J].
Costa, P ;
Manuel, J ;
Lobo, S .
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 2001, 13 (02) :123-133