Transdermal olarak uygulanacak ilaç yüklü formülasyonlar için yenilikçi üretim yöntemlerinin tasarımı ve etkinliklerinin incelenmesi
Küçük Resim Yok
Tarih
2017
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Ege Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Transdermal ilaç taşıyıcı sistemler, etkin maddenin deri aracılığıyla sistemik dolaşıma geçişini sağlayan ilaç uygulama yöntemlerindendir. Transdermal ilaç taşıyıcı sistemlerden olan yamalar ve mikro iğnelerin üretim tekniklerinde yenilikçi yaklaşımların geliştirildiği çalışmalarda etkin madde olarak montelukast sodyum (MS) kullanılmıştır. Üç boyutlu (3B) yazıcı filamentleri sıcak eriyik ekstrüzyon (SEE) yöntemi ile üretilmiştir. Filamentlerin mekanik dayanıklılıkları incelenmiş ardından 3B yazıcı ile yamaların üretiminde kullanılmıştır. MS ile ilgili karakterizasyon çalışmaları gerçekleştirilmiştir. MS için yüksek performanslı sıvı kromatografisi ile miktar tayini yöntemi geliştirilip valide edilmiştir. Zorlayıcı testlerde MS'nin ısı ve ışık maruziyetine karşı dayanıklılığı ölçülmüştür. FT-IR, DTK, TGA ve UV spektrumu analizlerinin yanı sıra çözünürlük, lipit/su partisyon katsayısı tayinleri de gerçekleştirilmiştir. Karakterizasyon çalışmalarının ardından MS yüklü yamalar 3B yazıcı ile üretilip, mekanik testler ve in vitro salım çalışması yapılmıştır. 3B yazıcılarda sıklıkla kullanılan poli(laktik asit) filamentler ve bu filamentlerle hazırlanan yamalar kıyaslama amacı ile kullanılmıştır. Sadece MS'den oluşan mikro iğneler kalıba döküm yöntemi ile üretilmiş ve maksimum yükleme kapasitesine ulaşılmıştır. Mikro iğneler ile görüntüleme çalışmalarını mekanik analizler izlemiştir. In vitro ve ex vivo salım çalışmaları yapılmıştır. Stabilite çalışmalarında MS miktarı ve mekanik özellikler incelenmiştir. Deri modelleri ile in vitro transdermal geçiş analizleri yapılmış, mikro iğnelerin keratinosit tabakasını aşabilme yeteneği incelenmiştir. MS'nin ve mikro iğnelerin biyouyumluluğunun incelenmesi için in vitro sitotoksisite ve irritasyon çalışmaları yapılmıştır. Mikro iğne uygulamasının ardından in vitro doku yüzeyi morfolojisi taramalı elektron mikroskobu ve model histolojisi için hematoksilen ve eozin boyama yöntemleri ile incelenmiştir. Çalışmalarımızın sonucunda sadece oral yol ile uygulanabilen farmasötik formları olan MS için yama ve mikro iğneler geliştirilmiştir. Transdermal uygulama ile MS'nin ilk geçiş etkisinden korunacağı ve biyoyararlanımın artacağı ayrıca oral yoldan ilaç alamayan hastalar için alternatif bir uygulama yolu oluşturacağı düşünülmektedir. Geliştirilen üretim yöntemleri ile farklı etkin maddeler de kullanılarak hastaların yaşam kalitesini artırmaya yönelik çeşitli transdermal ilaç taşıyıcı sistemlerin geliştirilebileceği öngörülmektedir
Transdermal drug delivery systems are one of the drug delivery systems, enabling the transport of the drug to the systemic circulation through the skin. Montelukast sodium (MS), was used as an active ingredient in our studies, which includes innovative approaches have been developed for the production techniques of patches and microneedles as transdermal drug delivery systems. Three-dimensional (3D) printer filaments were produced with hot melt extrusion (HME) method. The mechanical strengths of the filaments were investigated and used with the 3D printer for fabrication of patches. Characterization studies of MS was carried out. Quantitative determination of MS by high performance liquid chromatography has been developed and validated. As the stress tests, the stability of MS with heat and light exposure was investigated. In addition to the FT-IR, DSC, TGA and UV spectrum analyzes, solubility, lipid/water partition coefficient analyzes were also carried out. Following the characterization studies, MS loaded patches were produced with a 3D printer and mechanical tests and in vitro release studies were performed. Filaments made of poly(lactic acid) which are frequently used in 3D printers and the patches prepared by using these filaments were used for comparison. Microneedles made of pure MS were fabricated with molding method and maximum loading capacity was achieved. Imaging studies of microneedles were followed by mechanical analyzes. In vitro and ex vivo release studies were carried out. Stability of microneedles were examined in terms of MS amount and mechanical properties. In vitro transdermal permeation studies and ability of perforation of keratinocyte layer of microneedles were carried out with skin models. In vitro cytotoxicity and irritation studies were realized to investigate the biocompatibility of MS and microneedles. Morphology of the surface of the tissue was investigated with scanning electron microscope and histology studies were conducted with hematoxylin eosin staining methods. As the result of our studies, patches and microneedles have been developed for MS, which has only orally administered pharmaceutical forms. By transdermal administration of MS, the first pass effect would be avoided and the bioavailability would be increased additionally an alternative route of administration to the oral route may be constituted for the patients who cannot use oral route. It is envisaged that developed production methods, various transdermal drug delivery systems can be used with different active ingredients for improving the quality of patients.
Transdermal drug delivery systems are one of the drug delivery systems, enabling the transport of the drug to the systemic circulation through the skin. Montelukast sodium (MS), was used as an active ingredient in our studies, which includes innovative approaches have been developed for the production techniques of patches and microneedles as transdermal drug delivery systems. Three-dimensional (3D) printer filaments were produced with hot melt extrusion (HME) method. The mechanical strengths of the filaments were investigated and used with the 3D printer for fabrication of patches. Characterization studies of MS was carried out. Quantitative determination of MS by high performance liquid chromatography has been developed and validated. As the stress tests, the stability of MS with heat and light exposure was investigated. In addition to the FT-IR, DSC, TGA and UV spectrum analyzes, solubility, lipid/water partition coefficient analyzes were also carried out. Following the characterization studies, MS loaded patches were produced with a 3D printer and mechanical tests and in vitro release studies were performed. Filaments made of poly(lactic acid) which are frequently used in 3D printers and the patches prepared by using these filaments were used for comparison. Microneedles made of pure MS were fabricated with molding method and maximum loading capacity was achieved. Imaging studies of microneedles were followed by mechanical analyzes. In vitro and ex vivo release studies were carried out. Stability of microneedles were examined in terms of MS amount and mechanical properties. In vitro transdermal permeation studies and ability of perforation of keratinocyte layer of microneedles were carried out with skin models. In vitro cytotoxicity and irritation studies were realized to investigate the biocompatibility of MS and microneedles. Morphology of the surface of the tissue was investigated with scanning electron microscope and histology studies were conducted with hematoxylin eosin staining methods. As the result of our studies, patches and microneedles have been developed for MS, which has only orally administered pharmaceutical forms. By transdermal administration of MS, the first pass effect would be avoided and the bioavailability would be increased additionally an alternative route of administration to the oral route may be constituted for the patients who cannot use oral route. It is envisaged that developed production methods, various transdermal drug delivery systems can be used with different active ingredients for improving the quality of patients.
Açıklama
Anahtar Kelimeler
Eczacılık ve Farmakoloji, Pharmacy and Pharmacology