Design of pH-sensitive microspheres for the colonic delivery of the immunosuppressive drug tacrolimus

被引:73
作者
Lamprecht, A [1 ]
Yamamoto, H [1 ]
Takeuchi, H [1 ]
Kawashima, Y [1 ]
机构
[1] Gifu Pharmaceut Univ, Lab Pharmaceut Engn, Gifu 5028585, Japan
基金
日本学术振兴会;
关键词
microspheres; FK506; tacrolimus; colon delivery; pH-dependent; Eudragit;
D O I
10.1016/j.ejpb.2004.01.003
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Recently, tacrolimus was shown to be effective in mitigating inflammatory bowel disease (IBD). In the treatment of IBD, oral drug delivery using pH-dependent polymers is one of the most successful therapeutic strategies. Eudragit P-4135F, a pH-sensitive polymer for colonic delivery was used to prepare tacrolimus microparticles using an oil/oil emulsification or an oil/water emulsification technique combined with a solvent extraction or evaporation step. Although the pH-dependent drug release was similar for all types of microspheres, it was generally found that encapsulation rates of oil/water systems (extraction 38.8 +/- 9.4%; evaporation 56.3 +/- 1.9%) were superior to the oil/oil emulsification (4.8 +/- 0.4%). Eudragit P-4135F was found to limit drug leakage at pH 6.8 to levels lower than 10% within 6 h. At pH 7.4, almost immediate release (within 30 min) was observed. From differential scanning calorimetry and X-ray analyses, the drug inside the polymeric microsphere matrix was concluded to be present in a molecular dispersion. Generally, all formulations proved their applicability in vitro as a promising device for pH-dependent colonic delivery of tacrolimus, however, the oil/water technique was found to be superior to the oil/oil approach and among them solvent evaporation seemed to be more advisable, due to the higher encapsulation rate. (C) 2004 Elsevier B.V. All rights reserved.
引用
收藏
页码:37 / 43
页数:7
相关论文
共 21 条
[1]   Quantitative determination of tautomeric FK506 by reversed-phase liquid chromatography [J].
Akashi, T ;
Nefuji, T ;
Yoshida, M ;
Hosoda, J .
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, 1996, 14 (03) :339-346
[2]   Encapsulation of hydrophilic and lipophilic drugs in PLGA nanoparticles by the nanoprecipitation method [J].
Barichello, JM ;
Morishita, M ;
Takayama, K ;
Nagai, T .
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY, 1999, 25 (04) :471-476
[3]   COLONIC DELIVERY OF DEXAMETHASONE FROM A PRODRUG ACCELERATES HEALING OF COLITIS IN RATS WITHOUT ADRENAL SUPPRESSION [J].
FEDORAK, RN ;
HAEBERLIN, B ;
EMPEY, LR ;
CUI, N ;
NOLEN, H ;
JEWELL, LD ;
FRIEND, DR .
GASTROENTEROLOGY, 1995, 108 (06) :1688-1699
[4]  
Fellermann K, 1998, AM J GASTROENTEROL, V93, P1860
[5]   COLON-SPECIFIC DRUG DELIVERY [J].
FRIEND, DR .
ADVANCED DRUG DELIVERY REVIEWS, 1991, 7 (01) :149-199
[6]   GASTROINTESTINAL TRANSIT OF SMALL TABLETS IN PATIENTS WITH ULCERATIVE-COLITIS [J].
HARDY, JG ;
DAVIS, SS ;
KHOSLA, R ;
ROBERTSON, CS .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 1988, 48 (1-3) :79-82
[7]   Characterization of norfloxacine release from tablet coated with a new pH-sensitive polymer, P-4135F [J].
Hu, ZP ;
Shimokawa, T ;
Ohno, T ;
Kimura, G ;
Mawatari, SS ;
Kamitsuna, M ;
Yoshikawa, Y ;
Masuda, S ;
Takada, K .
JOURNAL OF DRUG TARGETING, 1999, 7 (03) :223-232
[8]   Application of Eudragit P-4135F for the delivery of ellagic acid to the rat lower small intestine [J].
Jeong, YI ;
Yv, RP ;
Ohno, T ;
Yoshikawa, Y ;
Shibata, N ;
Kato, S ;
Takeuchi, K ;
Takada, K .
JOURNAL OF PHARMACY AND PHARMACOLOGY, 2001, 53 (08) :1079-1085
[9]   Review article - Colonic drug targeting [J].
Kinget, R ;
Kalala, W ;
Vervoort, L ;
van den Mooter, G .
JOURNAL OF DRUG TARGETING, 1998, 6 (02) :129-149
[10]   Microsphere design for the colonic delivery of 5-fluorouracil [J].
Lamprecht, A ;
Yamamoto, H ;
Takeuchi, H ;
Kawashima, Y .
JOURNAL OF CONTROLLED RELEASE, 2003, 90 (03) :313-322