Design and in vitro evaluation of a novel bioadhesive vaginal drug delivery system for clotrimazole

被引:115
作者
Kast, CE [1 ]
Valenta, C [1 ]
Leopold, M [1 ]
Bernkop-Schnürch, A [1 ]
机构
[1] Univ Vienna, Inst Pharmaceut Technol & Biopharmaceut, A-1090 Vienna, Austria
关键词
chitosan; thiomers; vaginal adhesion; controlled release; clotrimazole;
D O I
10.1016/S0168-3659(02)00077-9
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
It was the purpose of this study to design and evaluate a new bioadhesive vaginal drug delivery system for clotrimazole. Chitosan, a cationic biopolymer derived by deacetylation of chitin, was modified by the introduction of thioglycolic acid (TGA). The modification was achieved by utilising a carbodiimide to link the carboxylic acid moieties of TGA covalently to the primary amino groups of chitosan. The amount of added carbodiimide was thereby varied, resulting in chitosan-TGA conjugates A and B with 160 muM (=mumol) and 280 muM thiol groups per gram polymer, respectively. In order to characterise the new polymers the water uptake, the disintegration behaviour, the bioadhesive properties utilising the rotating cylinder method, as well as the release of clotrimazole from tablets based on these derivatives were studied. The water uptake and cohesive properties of vaginal tablets consisting of these new conjugates could be significantly (p<0.05) improved. By adding clotrimazole the disintegration time of the conjugates was prolonged 1.6-fold for conjugate A and even 100-fold for conjugate B. Furthermore, the adhesion on vaginal mucosal tissue could be significantly improved. The addition of clotrimazole had also an impact on the adhesion time of chitosan-TGA conjugate B, which remained 26-times longer on vaginal mucosa than the corresponding unmodified polymer. The immobilisation of thiol groups guarantees a controlled drug release. Results of this study demonstrate that these new chitosan-TGA conjugates are very promising vehicles for the vaginal application of clotrimazole in treatment of mycotic infections. (C) 2002 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:347 / 354
页数:8
相关论文
共 19 条
[1]   Synthesis and characterisation of mucoadhesive thiolated polymers [J].
Bernkop-Schnürch, A ;
Steininger, S .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2000, 194 (02) :239-247
[2]  
Bernkop-Schnurch A., 2001, Scientia Pharmazeutica, V69, P109, DOI DOI 10.3797/SCIPHARM.AUT-01-12
[3]   Development of a mucoadhesive dosage form for vaginal administration [J].
Ceschel, GC ;
Maffei, P ;
Borgia, SL ;
Ronchi, C ;
Rossi, S .
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY, 2001, 27 (06) :541-547
[4]   INTRAVAGINAL DRUG DELIVERY [J].
DESHPANDE, AA ;
RHODES, CT ;
DANISH, M .
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY, 1992, 18 (11-12) :1225-1279
[5]   Pharmaceutical applications of chitosan [J].
Dodane, V ;
Vilivalam, VD .
PHARMACEUTICAL SCIENCE & TECHNOLOGY TODAY, 1998, 1 (06) :246-253
[6]   PRINCIPLE AND INVESTIGATION OF THE BIOADHESION MECHANISM OF SOLID DOSAGE FORMS [J].
DUCHENE, D ;
PONCHEL, G .
BIOMATERIALS, 1992, 13 (10) :709-714
[7]   Vaginal candidosis: epidemiological and etiological factors [J].
Ferrer, J .
INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS, 2000, 71 :S21-S27
[8]   ZERO-LENGTH CROSSLINKING PROCEDURE WITH THE USE OF ACTIVE ESTERS [J].
GRABAREK, Z ;
GERGELY, J .
ANALYTICAL BIOCHEMISTRY, 1990, 185 (01) :131-135
[9]  
Illum L, 1998, PHARM RES-DORDR, V15, P1326
[10]   Thiolated polymers -: thiomers:: development and in vitro evaluation of chitosan-thioglycolic acid conjugates [J].
Kast, CE ;
Bernkop-Schnürch, A .
BIOMATERIALS, 2001, 22 (17) :2345-2352