Publication: Matriks tipindeki transdermal terapötik sistemden kartoprilin difüzyonunun değerlendirilmesi
Abstract
1.ÖZET Kaptopril, antihipertansif olarak kullanılan, anjiotensin dönüştürücü enzim inhibitörlerinden (ACE) olup klinik uygulamaya ilk giren ajandır (145). Kaptopril, kısa plazma yarı ömrü (2-3 saat), düşük oral biyoyararlanımı, düşük erime derecesi (105- 108°C), düşük molekül ağırlığı gibi özellikleriyle transdermal terapötik sistem formülasyonları için uygun bir adaydır (157, 158). Transdermal terapötik sistemler, etkin maddenin kontrollü biçimde salımına olanak sağlayan ve kullanımı gittikçe yaygınlaşan sistemlerdir (97, 98). Piyasada kaptoprilin oral preparatları bulunmaktadır. Bu çalışmanın amacı, captopril için oral kullanıma alternatif olarak matriks tipte transdermal formülasyonlar geliştirmektir. Polimer olarak Eudragit RL 100 ve Eudragit RS 100’ün belli oranlardaki karışımıyla, plastifiyan olarak polietilen glikol 400 (PEG 400)’ün ve adhezif tabaka olarak poliizobütilenin (PIB) kullanıldığı, kaptopril içeren matriks tipindeki transdermal terapötik sistemler hazırlanmıştır. Farklı formülasyonlarda transdermal terapötik sitemlerin hazırlanmasından sonra Franz hücresiyle yapılan difüzyon çalışmalarında, kaptoprilin hidrofilik, hidrofobik membranlar ve insan epidermisinden difüzyonu araştırılmıştır. Yapılan in vitro çalışmalarda poliisobütilen tabakasının miktarı 0,5 g’dan 0,2 g’a düşürülerek antihipertansif etkinin sağlanması için gerekli olan kaptopril serbestleşmesi sağlanmıştır. Kaptoprilin etkili plazma seviyesi ise PIB’nin 0,2 g kullanıldığı FM 6 ve FM 7 formülasyonlarıyla elde edilmiştir. Eudragit, Kaptopril, Poliizobütilen, Sentetik Membran, Transdermal Terapötik Sistemler 2.
Diffusion of Captopril From A Matrix Type Transdermal Therapeutic System Captopril is the first Angiotensin Converting Enzyme (ACE) inhibitor in clinically used (145) it is a good candidate for transdermal therapeutic system formulations. Because it has short half life (about 2 or 3 hours), low oral bioavailability, low melting point and low molecular weight (157- 158). Transdermal therapeutic systems are increasingly used among common topical pharmaceutical forms which provides a controlled release of the drug to the patient (97-98). Oral preparations of captopril are available in markets. The aim of this study was developed matrix type transdermal formulations of this drug as alternative to the oral routes. Matrix type of transdermal therapeutic systems having captopril as active ingredient, Eudragit RL 100 and Eudragit RS 100 as polymers, polyethylene glycol 400 (PEG 400) as plasticizer, polyisobuthylene (PIB) as adhesive layer were used. After preparing the transdermal therapeutic systems with different formulations, the diffusion of captopril was investigated by using hydrophilic, hydrophobic synthetic membranes and human epidermis from Franz cell. The polyisobuthylene layer was reduce the 0,2 g in order to obtain antihypertansive effect in in vitro studies using captopril in 0,5 g PIB formulation. Becouse of the in sufficient release of captopril. Active plasma level of captopril was obtained by using 0,2 g PIB layer in FM 6 and FM 7 formulations. Key words: Eudragit, Captopril, Polyisobuthylene, Synthetic membrane, Transdermal Therapeutic Systems
Diffusion of Captopril From A Matrix Type Transdermal Therapeutic System Captopril is the first Angiotensin Converting Enzyme (ACE) inhibitor in clinically used (145) it is a good candidate for transdermal therapeutic system formulations. Because it has short half life (about 2 or 3 hours), low oral bioavailability, low melting point and low molecular weight (157- 158). Transdermal therapeutic systems are increasingly used among common topical pharmaceutical forms which provides a controlled release of the drug to the patient (97-98). Oral preparations of captopril are available in markets. The aim of this study was developed matrix type transdermal formulations of this drug as alternative to the oral routes. Matrix type of transdermal therapeutic systems having captopril as active ingredient, Eudragit RL 100 and Eudragit RS 100 as polymers, polyethylene glycol 400 (PEG 400) as plasticizer, polyisobuthylene (PIB) as adhesive layer were used. After preparing the transdermal therapeutic systems with different formulations, the diffusion of captopril was investigated by using hydrophilic, hydrophobic synthetic membranes and human epidermis from Franz cell. The polyisobuthylene layer was reduce the 0,2 g in order to obtain antihypertansive effect in in vitro studies using captopril in 0,5 g PIB formulation. Becouse of the in sufficient release of captopril. Active plasma level of captopril was obtained by using 0,2 g PIB layer in FM 6 and FM 7 formulations. Key words: Eudragit, Captopril, Polyisobuthylene, Synthetic membrane, Transdermal Therapeutic Systems