Publication: L-tiroksin sodyum içeren transdermal terapötik sistem hazırlanması ve değerlendirilmesi
Abstract
Transdermal terapötik sistemler ile ilaç verilişi, konvansiyonel metotlara göre birçok avantaja sahiptir. Bu çalışmada etkin madde olarak, Levotiroksin sodyum ile bir transdermal terapötik sistem (TTS) hazırlanması amaçlanmıştır. Bunun için farklı polimerler kullanılmak suretiyle matriks tipi kontrollü salım sistemleri hazırlanmıştır. Formülasyonlarda kullanılacak polimerin seçiminde öncelikli olarak literatürde kayıtlı ve sıklıkla kullanılan polimerler tercih edilmiştir. Seçilen sentetik polimer: Eudragit RL 100, yarı sentetik polimer: Hidroksipropil Metil Selüloz (HPMC) 4000 ve doğal polimerler: Pektin, Skleroglukan ve Sodyum Aljinat’tır. Yapılan ön formülasyon çalışmaları sonucunda HPMC 4000 ve Eudragit RL 100 için plastifiyan ilavesi gerekli görülmüştür. Bu polimerler için kullanılması uygun plastifiyanlar sırasıyla HPMC 4000 için Gliserin ile Eudragit RL 100 için Polietilen glikol (PEG) 400 şeklinde seçilmiştir. Böylelikle yeterli esneklikte, kırılgan olmayan, homojen ve görsel olarak uygun TTS ler elde edilmiştir. Bundan sonraki aşama, tablet formunda yardımcı maddeler ile geçimsizlik eğiliminde olan Levotiroksin sodyum’un, hazırlanan formülasyonlardaki polimer ve yardımcı maddeler ile geçimliliğini saptamak olmuştur. Bu amaçla, bir dizi diferansiyel taramalı kalorimetri (DSC) analizi ve bunları destekleyici Fourier transform infrared spektroskopi (FTIR) ile hızlı ve güvenilir bir tarama yapılmıştır. Sonuçta elde edilen veriler ve literatür ile karşılaştırılarak yapılan yorumlar doğrultusunda, başlangıçta önerilen polimerlerden hiçbiri Levotiroksin sodyum etkin maddesi ile geçimsizlik göstermemektedir. Aynı durum, seçilen plastifiyanlarla yapılan tarama sonuçları için de geçerlidir. Etkin maddenin polimer formülasyonlarından salım profilini incelemek ve kontrollü salımını denetlemek amacıyla yukarıda bahsi geçen farklı polimerlerle in-vitro farmakope denetimleri uygulanmıştır. Sonuç olarak kullanılan tüm polimerlerin levotiroksin sodyum için transdermal terapötik sistem hazırlanması için uygun olduğu görülmüştür.
Transdermal drug delivery has many advantages over the conventional drug delivery routes. The aim of this study was to prepare a transdermal therapeutic system containing Levothyroxine sodium. In order to achieve this aim, matrix type controlled release systems were prepared using various kinds of polymers. While selecting the polymers to be used in the formulations, the most common polymers used in the literature were of first priority. The synthetic polymer chosen was: Eudragit RL 100, the semi synthetic polymer was HPMC 4000 and the natural ones were: Pectin, Scleroglucane, Sodium alginate. During the preformulation study, it was found out that, there was a need of plasticizer for the HPMC 4000 and Eudragit RL 100 formulations. The appropriate plasticizers to be used are stated in the literature and were selected respectively as Glycerin for HPMC 4000 and PEG 400 for Eudragit RL 100. Thus, transdermal therapeutic systems flexible enough, non-fragile and visually appropriate were obtained. As a next step, the compatibility of Levothyroxine sodium with the polymers and excipients used in the formulations was detected, since it has tendency to show incompatibility with the excipients in tablet form. Thus, a series of DSC analyzes and supportive FTIR spectroscopy were used for fast and reliable scanning. The data obtained and the comments made according to literature showed that all of the proposed polymers were compatible with the drug substance. The same counts for the scanning results obtained for the plasticizers chosen. In order to examine the release profile of the drug substance from the polymer formulations and to ensure controlled release, in-vitro compendial methods were applied to all the TTS prepared using the aforementioned polymers. As a result it can be stated that all of the polymers used in this study are suitable for preparing a levothyroxine sodium transdermal therapeutic system
Transdermal drug delivery has many advantages over the conventional drug delivery routes. The aim of this study was to prepare a transdermal therapeutic system containing Levothyroxine sodium. In order to achieve this aim, matrix type controlled release systems were prepared using various kinds of polymers. While selecting the polymers to be used in the formulations, the most common polymers used in the literature were of first priority. The synthetic polymer chosen was: Eudragit RL 100, the semi synthetic polymer was HPMC 4000 and the natural ones were: Pectin, Scleroglucane, Sodium alginate. During the preformulation study, it was found out that, there was a need of plasticizer for the HPMC 4000 and Eudragit RL 100 formulations. The appropriate plasticizers to be used are stated in the literature and were selected respectively as Glycerin for HPMC 4000 and PEG 400 for Eudragit RL 100. Thus, transdermal therapeutic systems flexible enough, non-fragile and visually appropriate were obtained. As a next step, the compatibility of Levothyroxine sodium with the polymers and excipients used in the formulations was detected, since it has tendency to show incompatibility with the excipients in tablet form. Thus, a series of DSC analyzes and supportive FTIR spectroscopy were used for fast and reliable scanning. The data obtained and the comments made according to literature showed that all of the proposed polymers were compatible with the drug substance. The same counts for the scanning results obtained for the plasticizers chosen. In order to examine the release profile of the drug substance from the polymer formulations and to ensure controlled release, in-vitro compendial methods were applied to all the TTS prepared using the aforementioned polymers. As a result it can be stated that all of the polymers used in this study are suitable for preparing a levothyroxine sodium transdermal therapeutic system