Self-nanoemulsifying drug delivery systems of tamoxifen citrate: Design and optimization

被引:261
作者
Elnaggar, Yosra S. R. [1 ]
El-Massik, Magda A. [1 ]
Abdallah, Ossama Y. [1 ]
机构
[1] Univ Alexandria, Fac Pharm, Dept Pharmaceut, Alexandria, Egypt
关键词
Tamoxifen citrate; SNEDDS; Caproyl; 90; Maisine; 35-1; Cremophor RH40; ORAL DELIVERY; FORMULATIONS; BIOAVAILABILITY; SOLUBILITY; ABSORPTION; SNEDDS;
D O I
10.1016/j.ijpharm.2009.07.015
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Tamoxifen citrate is an antiestrogen for peroral breast cancer treatment. The drug delivery encounters problems of poor water solubility and vulnerability to enzymatic degradation in both intestine and liver. In the current study, tamoxifen citrate self-nanoemulsifying drug delivery systems (SNEDDS) were prepared in an attempt to circumvent such obstacles. Preliminary screening was carried out to select proper ingredient combinations. All surfactants screened were recognized for their bioactive aspects. Ternary phase diagrams were then constructed and an optimum system was designated. Three tamoxifen SNEDDS were then compared for optimization. The systems were assessed for robustness to dilution, globule size, cloud point, surface morphology and drug release. An optimum system composed of tamoxifen citrate (1.6%), Maisine 35-1 (16.4%), Caproyl 90 (32.8%), Cremophor RH40 (32.8%) and propylene glycol (16.4%) was selected. The system was robust to different dilution volumes and types. It possessed a mean globule size of 150 nm and a cloud point of 80 degrees C. Transmission electron microscopy demonstrated spherical particle morphology. The drug release from the selected formulation was significantly higher than other SNEDDS and drug suspension, as well. Realizing drug incorporation into an optimized nano-sized SNEDD system that encompasses a bioactive surfactant, our results proposed that the prepared system could be promising to improve oral efficacy of the tamoxifen citrate. (C) 2009 Elsevier B.V. All rights reserved.
引用
收藏
页码:133 / 141
页数:9
相关论文
共 22 条
[1]   Lipid excipients and delivery systems for pharmaceutical development: A regulatory perspective [J].
Chen, Mei-Ling .
ADVANCED DRUG DELIVERY REVIEWS, 2008, 60 (06) :768-777
[2]   Increasing the proportional content of surfactant (Cremophor EL) relative to lipid in self-emulsifying lipid-based formulations of danazol reduces oral bioavailability in beagle dogs [J].
Cuine, Jean F. ;
Charman, William N. ;
Pouton, Colin W. ;
Edwards, Glenn A. ;
Porter, Christopher J. H. .
PHARMACEUTICAL RESEARCH, 2007, 24 (04) :748-757
[3]   Design and evaluation of self-nanoemulsifying drug delivery systems (SNEDDS) for cefpodoxime proxetil [J].
Date, Abhijit A. ;
Nagarsenker, M. S. .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2007, 329 (1-2) :166-172
[4]   In vitro percutaneous absorption enhancement of a lipophilic drug tamoxifen by terpenes [J].
Gao, S ;
Singh, J .
JOURNAL OF CONTROLLED RELEASE, 1998, 51 (2-3) :193-199
[5]   Self-emulsifying drug delivery systems (SEDDS) for improved oral delivery of lipophilic drugs [J].
Gursoy, RN ;
Benita, S .
BIOMEDICINE & PHARMACOTHERAPY, 2004, 58 (03) :173-182
[6]   A novel emulsifier, Labrasol, enhances gastrointestinal absorption of gentamicin [J].
Hu, ZP ;
Tawa, R ;
Konishi, T ;
Shibata, N ;
Takada, K .
LIFE SCIENCES, 2001, 69 (24) :2899-2910
[7]   Improvement of physicochemical properties of N-4472 part I formulation design by using self-micro emulsifying system [J].
Itoh, K ;
Tozuka, Y ;
Oguchi, T ;
Yamamoto, K .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2002, 238 (1-2) :153-160
[8]   Tarnoxifen citrate loaded amphiphilic β-cyclodextrin nanoparticles:: In vitro characterization and cytotoxicity [J].
Memisoglu-Bilensoy, E ;
Vural, L ;
Bochot, A ;
Renoir, JM ;
Duchene, D ;
Hincal, AA .
JOURNAL OF CONTROLLED RELEASE, 2005, 104 (03) :489-496
[9]   Hydrogel-thickened nanoemulsion system for topical delivery of lipophilic drugs [J].
Mou, Dongsheng ;
Chen, Huabing ;
Du, Danrong ;
Mao, Chengwen ;
Wan, Hangling ;
Xu, Huibi ;
Yang, Xiangliang .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2008, 353 (1-2) :270-276
[10]   Solid lipid nanoparticles (SLN) for controlled drug delivery -: a review of the state of the art [J].
Müller, RH ;
Mäder, K ;
Gohla, S .
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, 2000, 50 (01) :161-177