Publication: Skleroglukan ile çok partiküllü sistemler hazırlanması ve in vitro değerlendirilmesi
Abstract
1.ÖZET SKLEROGLUKAN İLE ÇOK PARTİKÜLLÜ SİSTEMLER HAZIRLANMASI VE IN VITRO DEĞERLENDİRİLMESİ Bu çalışmada doğal bir polimer olan skleroglukan ile çok partiküllü ilaç taşıyıcı sistemler hazırlanmıştır. Model ilaç olarak suda çözünen (propranolol hidroklorür) ve pratik olarak suda çözünmeyen (pindolol) etkin madde olarak seçilmiştir. Skleroglukan ile çok partiküllü sistemlerin hazırlanmasında uygun yöntemin saptanmasına ait denemeler için, ilk olarak emülsiyon yöntemi seçilmiştir. Çapraz bağlayıcı kullanılmadan yapılan çalışmalar sonucunda mikropartiküller elde edilememiştir. Yöntemlerden biri olan boncuk şeklinde damlatma yöntemi ile skleroglukan boncukları hazırlanmıştır. Önceden şişirilerek hazırlanan % 1'lik skleroglukan müsilajı iç faz olarak, % 3'lük sulu boraks çözeltisi ise dış faz olarak kullanılmıştır. Plastik damlalık yardımı ile iç fazın dış faza damlatılması ile hazırlanan boncuklar, absolü alkolde bekletilerek sertleştirilmiş ve oda sıcaklığında kurumaya bırakılmışlardır. Etkin madde içermeyen boncukların kuruduktan sonra küresel şekillerini koruyamamaları boncukların hazırlanmasında polimer:etkin madde oranının önemli bir parametre olduğunu göstermiştir. 1:3 (polimer:etkin madde) oranında propranolol hidroklorür veya pindolol içerecek şekilde hazırlanan boncuklar ile başarılı sonuçlar elde edilmiştir. Propranolol hidroklorür taşıyan boncukların % ilaç tutulmalarının düşük olması sebebi ile bu boncuklar soğuk absolü alkol ile hazırlanarak ilaç tutma kapasiteleri artırılmıştır. Elde edilen skleroglukan boncukların ilaç salım profilleri incelenmiştir. Boncuklardan hızlı şekilde gerçekleşen ilaç salımını kontrol etmek amacı ile hazırlanan formülasyonlara farklı viskozitelere sahip HPMC türleri ilave edilmiştir. İç fazın viskozite değerinin damlatma açısından önemli olması nedeni ile 1:1, 3:2, 4:1 (skleroglukan:HPMC) oranında HPMC 100000 veya HPMC E 5 içeren formülasyonlar, propranolol hidroklorür taşıyan boncuklar için hazırlanmış ancak ilaç salım hızlarında anlamlı bir farklılık görülmemiştir. Pindolol içeren boncuk formülasyonlarına, boncukların kuruduktan sonra şekillerini kaybetmeleri sebebi ile HPMC ilave edilememiştir. 2.
PREPARATİON AND İN VİTRO EVALUATİON OF MULTİPARTİCULATE SYSTEMS WİTH SCLEROGLUCAN In this study, multiparticulate drug carrier systems were prepared with a natural polymer, scleroglucan. A water soluble drug, propranolol hydrochloride and a pratically water insoluble drug, pindolol were chosen as model drugs. To determine the suitable method, firstly the emulsion method was chosen for preparing multiparticulate systems with scleroglucan. Multiparticles could not be obtained by preparing them without using a cross linking agent. Scleroglucan beads were prepared by dropping method which is another method used for the preparation of beads. Previously swelled 1 % scleroglucan gel was used as the inner phase, 3 % borax solution in water was used as the outer phase. By dropping the inner phase into the outer phase with a plastic dropper, the beads were prepared, then they were put into absolute alcohol for hardening and were allowed to dry at room temperature. Beads without a drug couldn't keep their spherical shapes, indicating that the polymer:drug ratio is an important parameter in the preparation of beads. Successful results were gained with the beads containing 1:3 (polymer:drug) propranolol hydrochloride or pindolol. As the encapsulation efficiencies of beads containing propranolol hydrochloride were low, these beads were put in cold absolute alcohol to prevent the loss of propranolol hydrochloride by dissolving in alcohol this for enchancing their encapsulation efficiency. Dissolution profiles of the scleroglucan beads were examined and for controlling the drug release from the beads, HPMC types having different viscosities were added the formulations. Because of the importance of the viscosity of the inner phase in dropping, formulations containing HPMC 100000 and HPMC E 5 in the ratio of 1:1, 3:2, 4:1 (scleroglucan:HPMC) were prepared for beads containing propranolol hydrochloride. Adding HPMC didn't cause a significant difference on their in vitro dissolution profiles. HPMC coudn't be added into the pindolol beads as they lost their shapes during the drying phase.
PREPARATİON AND İN VİTRO EVALUATİON OF MULTİPARTİCULATE SYSTEMS WİTH SCLEROGLUCAN In this study, multiparticulate drug carrier systems were prepared with a natural polymer, scleroglucan. A water soluble drug, propranolol hydrochloride and a pratically water insoluble drug, pindolol were chosen as model drugs. To determine the suitable method, firstly the emulsion method was chosen for preparing multiparticulate systems with scleroglucan. Multiparticles could not be obtained by preparing them without using a cross linking agent. Scleroglucan beads were prepared by dropping method which is another method used for the preparation of beads. Previously swelled 1 % scleroglucan gel was used as the inner phase, 3 % borax solution in water was used as the outer phase. By dropping the inner phase into the outer phase with a plastic dropper, the beads were prepared, then they were put into absolute alcohol for hardening and were allowed to dry at room temperature. Beads without a drug couldn't keep their spherical shapes, indicating that the polymer:drug ratio is an important parameter in the preparation of beads. Successful results were gained with the beads containing 1:3 (polymer:drug) propranolol hydrochloride or pindolol. As the encapsulation efficiencies of beads containing propranolol hydrochloride were low, these beads were put in cold absolute alcohol to prevent the loss of propranolol hydrochloride by dissolving in alcohol this for enchancing their encapsulation efficiency. Dissolution profiles of the scleroglucan beads were examined and for controlling the drug release from the beads, HPMC types having different viscosities were added the formulations. Because of the importance of the viscosity of the inner phase in dropping, formulations containing HPMC 100000 and HPMC E 5 in the ratio of 1:1, 3:2, 4:1 (scleroglucan:HPMC) were prepared for beads containing propranolol hydrochloride. Adding HPMC didn't cause a significant difference on their in vitro dissolution profiles. HPMC coudn't be added into the pindolol beads as they lost their shapes during the drying phase.