Publication: Antihipertansif etkin madde içeren ve farklı salım kinetiğine sahip katı dozaj şekillerinin hazırlanması ve in vitro değerlendirilmesi
Abstract
Amaç: Bu tez çalışmasında amaç, hipertansiyon tedavisinde hasta uyuncunu artırmak hedefiyle iki farklı salım kinetiği gösteren preparat uygulanarak, dozlama arasındaki Amlodipin Besilat plazma ilaç konsantrasyonundaki dalgalanmanın üstesinden gelmek için Amlodipin Besilat içeren hızlı salımlı tablet ve uzatılmış salimli tablet formülasyonları geliştirilmektir. Gereç ve Yöntem: 6 mm çapındaki tabletler direkt basım ile hazırlanmıştır. Tabletlerin geliştirilmesinde Amlodipin Besilat, Kollidon CL, Primojel, Avicel PH-102, Kırmızı Demir Oksit, Magnezyum Stearat, Mannitol, HPC-M ve HPC-SL kullanılmıştır. Dissolüsyon dahil olmak üzere in vitro tablet kontrolleri yapılmıştır. Tablet dissolüsyonları SOTAX AT 7 cihazında FDA kılavuzu doğrultusunda USP palet karıştırıcı, 50 RPM, 37 2 ° C, 900 mL pH 2 (IR tabletler için 1 saat, ER tabletler için 2 saat), pH 6,8 (ER tabletler için pH 2 ortamında 2 saatin ardında 10 saat) dissolüsyon ortamında gerçekleştirilmiştir. Numuneler 238 nm’de Mettler Toledo UV5 cihazında okunmuş ve dissolüsyon ortamına geçen ilaç miktarları hesaplanmıştır. Bulgular: Hızlı salım formülasyonlarında (IR) süperdağıtıcı ile seyrelticilerin; uzatılmış salım formülasyonlarında (ER) HPC-M, HPC-SL polimerlerinin dissolüsyona olan etkileri incelenmiştir.Sonuç: 9 IR tablet formülasyonu arasından 5. dakikada en yüksek ilaç salımı gösteren formülasyon optimum formülasyonu kabul edilip IR-5 formülasyon seçilmiştir. Geliştirilen 6 adet ER tabletlerinin ilaç salım kinetikleri DDSolver ile saptanmıştır. 12. saat sonunda %50 ilaç salıma en yakın salım gösteren ER-1 ve ER-4 tabletleri arasından Higuchi kinetiği ile salım yapan ER-1 nihai formülasyon olarak seçilmiştir. Oluşturulan 9 IR tablet formülasyonunda değişik oranlarda bulunan süper dağıtıcılar ile dolgu maddelerinin dissolüsyona ve tablet özelliklerine etkisi incelenmiştir. Oluşturulan ER tabletlerin de kullanılan HPC SL, HPC M polimer oranlarının dissolüsyona etkisi incelenmiştir.
Objective: The aim of this thesis study is to increase patient compliance in the treatment of hypertension, to develop immediate-release tablets (IR) and extended release tablet (ER) formulations containing amlodipine besylate to overcome the fluctuation in Amlodipine Besylate plasma drug concentrations between dosing intervals by applying two different release kinetics. Material and Method: Tablets with a diameter of 6 mm were prepared by direct compression method. Amlodipine Besylate, Kollidon CL, Primojel, Avicel PH-102, Red Iron Oxide, Magnesium Stearate, Mannitol, HPC-M and HPC-SL were used in the development of tablets. In vitro tablet controls, including dissolution, were performed. The dissolution study, according to FDA guide, was conducted in USP paddle apparatus at 50 RPM and in Sotax dissolution device, at a temperature of 37 2 °C in a 900 mL dissolution medium. The dissolution media for IR tablets was pH 2 for 1 hour, the dissolution media for ER tablets was pH 2 for 2 hours and afterwards was pH 6.8 for 10 hours. The amount of AML released into the dissolution media was measured by Mettler Toledo UV 5 at a wavelength of 238 nm.Results: In immediate release formulations, superdisintegrant and diluents; In extended release formulations, the effects of HPC-M & HPC-SL polymers on dissolution were investigated.Discussion: Among the 9 different IR tablet formulations, the formulation showing the highest drug release in 5th minute was accepted as the optimum formulation, which is the IR-5. The drug release kinetics of the extended-release tablets were examined by using DDSolver programme. At the end of the 12th hour, ER-1 and ER-4 tablets showed the nearest release of 50% drug release. Among them, ER-1, which was released following the Higuchi kinetics was chosen as the final formulation.
Objective: The aim of this thesis study is to increase patient compliance in the treatment of hypertension, to develop immediate-release tablets (IR) and extended release tablet (ER) formulations containing amlodipine besylate to overcome the fluctuation in Amlodipine Besylate plasma drug concentrations between dosing intervals by applying two different release kinetics. Material and Method: Tablets with a diameter of 6 mm were prepared by direct compression method. Amlodipine Besylate, Kollidon CL, Primojel, Avicel PH-102, Red Iron Oxide, Magnesium Stearate, Mannitol, HPC-M and HPC-SL were used in the development of tablets. In vitro tablet controls, including dissolution, were performed. The dissolution study, according to FDA guide, was conducted in USP paddle apparatus at 50 RPM and in Sotax dissolution device, at a temperature of 37 2 °C in a 900 mL dissolution medium. The dissolution media for IR tablets was pH 2 for 1 hour, the dissolution media for ER tablets was pH 2 for 2 hours and afterwards was pH 6.8 for 10 hours. The amount of AML released into the dissolution media was measured by Mettler Toledo UV 5 at a wavelength of 238 nm.Results: In immediate release formulations, superdisintegrant and diluents; In extended release formulations, the effects of HPC-M & HPC-SL polymers on dissolution were investigated.Discussion: Among the 9 different IR tablet formulations, the formulation showing the highest drug release in 5th minute was accepted as the optimum formulation, which is the IR-5. The drug release kinetics of the extended-release tablets were examined by using DDSolver programme. At the end of the 12th hour, ER-1 and ER-4 tablets showed the nearest release of 50% drug release. Among them, ER-1, which was released following the Higuchi kinetics was chosen as the final formulation.