PREPARATION AND IN-VITRO CHARACTERIZATION OF FLOATING-PULSATILE HOLLOWBEADS CONTAINING INDOMETHACIN

Öz

Objective: Objective: Designing matrix structured controlled release systems using polymers or waxy lipids is a popular option today. Hollowbeads are formulations characterized by the formation of an air-filled cavity inside. In our study, indomethacin was chosen as a model drug. Cetyl alcohol was selected to create the hollowbeads structure, and NaCMC was chosen to achieve long-term release. Kollicoat® MAE100P was used to reduce and/or prevent ulcer formation and control release.
Material and Method: The formulations were prepared using a new “wax removal” technique. Different concentrations of ZnCl2 and CaCl2 were used as crosslinkers. In the preformulation studies, 24 different formulations were prepared by changing the amount of NaCMC, the amount of crosslinker, and the crosslinking time. The structure, size, encapsulation efficiency, yield, hollow structure, and long-term release capacity were investigated in the formulations. These parameters were statistically evaluated depending on the amount of NaCMC, the type of crosslinker, the amount of crosslinker, and contact times with the crosslinker.
Result and Discussion: Hollowbeads were characterized by SEM and FT-IR. In vitro release studies, release kinetics, and release mechanisms were performed in pH 1.2 HCl and pH 6.8 phosphate buffer media. Swelling, and buoyancy studies were performed. The long-term stability, encapsulation efficiencies, drug loading efficiencies, and yields of the formulations were also evaluated. Two promising formulations (F2 and F19) were found to be able to release indomethacin in both the stomach and intestinal media for 24 hours.

Anahtar Kelimeler

• Controlled release
• hollowbeads
• indomethacin
• polymer
• wax removal

İNDOMETAZİN İÇEREN YÜZEN-PULSATİL İÇİ BOŞ BONCUKLARIN HAZIRLANMASI VE İN-VİTRO KARAKTERİZASYONU

Öz

Amaç: Polimerlerin veya mumsu lipidlerin kullanılması ile matriks yapılı kontrollü salım sağlayan sistemler tasarlamak günümüzde popüler bir seçenektir. İçi boş boncuklar (hollowbeads), içinde hava dolu bir boşluğun oluşması ile karakterize formülasyonlardır. Çalışmamızda, indometazin model ilaç olarak seçilmiştir. Hollowbeads yapısını oluşturmak için setil alkol ve uzun süreli salım elde edebilmek için de NaCMC seçilmiştir. Ülser oluşumunu azaltmak ve/veya önlemek ve salımı kontollü elde etmek için Kollicoat® MAE100P kullanılmıştır.
Gereç ve Yöntem: Formülasyonlar, yeni bir teknik olan “wax removol” tekniği kullanılarak hazırlanmıştır. Çapraz bağlayıcı olarak ZnCl2 ve CaCl2’nin farklı konsantrasyonları kullanılmıştır. Önformülasyon çalışmalarında, NaCMC miktarı, çapraz bağlayıcı miktarı ve çapraz bağlanma sürelerini de değiştirerek 24 farklı formülasyon hazırlanmıştır. Formülasyonların yapısı, boyutu, enkapsülasyon etkinliği, verimi, hollow yapısı, uzun süreli salım kapasiteleri incelenmiştir. Bu parametreler NaCMC miktarına, çapraz bağlayıcı tipine, çapraz bağlayıcı miktarına ve çapraz bağlayıcıyla olan temas sürelerine bağlı olarak istatistiksel olarak değerlendirilmiştir.
Sonuç ve Tartışma: Hollowbeads’ler, SEM ve FT-IR ile karakterize edilmiştir. pH 1.2 HCl ve pH 6.8 fosfat tamponu ortamlarında in vitro salım, şişme ve yüzme çalışmaları gerçekleştirilmiştir. Salım kinetikleri ve salım mekanizmaları açıklanmıştır. Formülasyonların uzun süreli stabiliteleri, enkapsülasyon etkinlikleri, ilaç yükleme etkinlikleri ve verimleri de değerlendirilmiştir. Umut vadeden iki formülasyonun (F2 ve F19), 24 saat süreyle hem mide hem de bağırsak ortamında indometazin salımı gerçekleştirebildiği tespit edilmiştir.

Anahtar Kelimeler

• İndometazin
• kontrollü salım
• mum yerdeğiştirme
• oyuk boncuk
• polimer

Kaynakça

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