Publication: Donepezil hidroklorür içeren ağızda dağılan filmlerin hazırlanması ve değerlendirilmesi
Abstract
Bu tez çalışmasında etken madde olarak donepezil HCl ve ana polimer olarak lycoat ve pullulan polimerleri kullanılarak Alzheimer ve demans tedavisinde kullanılabilecek hızlı, güvenilir, etkili ve yenilikçi bir dozaj formu olan ağızda dağılan film (ADF) formülasyonlarının hazırlanması amaçlanmıştır. Çözücü dökme yöntemi ile filmleri hazırlayıp karakterizasyon çalışmalarını yapmadan önce etken maddenin fizikokimyasal özelliklerinin stabilitesini anlamak üzere validasyon çalışmaları yapılmıştır. Bu amaçla öncelikle, donepezil HCl’nin çözünürlük, erime, FT-IR ve UV-spektrum çalışmaları tamamlanmıştır. Ardından ADF’lerin karakterizasyon çalışmaları amacıyla; morfolojik tayin, verim, dağılma süresi tayini, kalınlık tayini, katlanma tayini, şişme tayini, kütle tekdüzeliği tayini, içerik tekdüzeliği tayini, pH tayini, nem içeriği tayini ve in vitro salım tayini gerçekleştirilmiştir. Sonuçlar istatiksel olarak karşılaştırılmıştır. Daha sonra, en iyi olduğu değerlendirilen F-16 ADF formülasyonunun gerilme direnci, elastik modülü (Young modülü) ve uzama yüzdesi tayinleri de gerçekleştirilmiştir. Validasyon çalışmalarına göre, bu çalışmada kullanılacak etken madde analizleri uygun bulunmuştur. Karakterizasyon sonuçlarına göre başarılı ADF’ler geliştirilebilmiştir. Çalışma sonucunda, F-5, F-9, F-12, F-14 ve F-16 olmak üzere 5 adet optimum ADF formülasyonu başarıyla elde edilmiştir.
In this thesis, it was aimed to prepare orally disintegrating film (ODF) formulations, which is a fast, safe, effective, and innovative dosage form that can be used in the treatment of Alzheimer's disease and dementia, using donepezil HCl as the active pharmaceutical ingredient and lycoat and pullulan polymers as the main polymer. Before preparing the films with the solvent casting method and performing the characterization studies, validation studies were carried out to understand the stability of the physicochemical properties of the active pharmaceutical ingredient. For this purpose, firstly, solubility, melting point, FT-IR, and UV-spectrum studies of donepezil HCl were completed. Then, for the characterization studies of ODFs; determination of morphology, determination of disintegration time, determination of thickness, determination of folding endurance, determination of swelling, determination of mass uniformity, determination of content uniformity, determination of pH, determination of moisture content, and in vitro release studies were performed. The results were compared statistically. Then, the tensile strength, elastic modulus (Young's modulus), and percent elongation determinations of the F-16 ADF formulation, which was considered to be the best, were also performed. According to the validation studies, the active pharmaceutical ingredient analyses to be used in this study were found appropriate. Successful ODFs have been developed according to the characterization results. As a result of the study, 5 optimum ODF formulations were successfully obtained as F-5, F-9, F-12, F-14 and F-16.
In this thesis, it was aimed to prepare orally disintegrating film (ODF) formulations, which is a fast, safe, effective, and innovative dosage form that can be used in the treatment of Alzheimer's disease and dementia, using donepezil HCl as the active pharmaceutical ingredient and lycoat and pullulan polymers as the main polymer. Before preparing the films with the solvent casting method and performing the characterization studies, validation studies were carried out to understand the stability of the physicochemical properties of the active pharmaceutical ingredient. For this purpose, firstly, solubility, melting point, FT-IR, and UV-spectrum studies of donepezil HCl were completed. Then, for the characterization studies of ODFs; determination of morphology, determination of disintegration time, determination of thickness, determination of folding endurance, determination of swelling, determination of mass uniformity, determination of content uniformity, determination of pH, determination of moisture content, and in vitro release studies were performed. The results were compared statistically. Then, the tensile strength, elastic modulus (Young's modulus), and percent elongation determinations of the F-16 ADF formulation, which was considered to be the best, were also performed. According to the validation studies, the active pharmaceutical ingredient analyses to be used in this study were found appropriate. Successful ODFs have been developed according to the characterization results. As a result of the study, 5 optimum ODF formulations were successfully obtained as F-5, F-9, F-12, F-14 and F-16.