Application of mixtures of polymeric carriers for dissolution enhancement of fenofibrate using hot-melt extrusion

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• 作者：Adela Kalivoda^a ; ^b ; ^{Adela.Kalivoda@merckgroup.com} ; Matthias Fischbach^a ; ^{Matthias.Fischbach@merckgroup.com} ; Peter Kleinebudde^b ; ^{Kleinebudde@hhu.de} ; ^{kleinebudde@uni-duesseldorf.de}
• 关键词：Solid dispersion ; Hot-melt extrusion ; Fenofibrate ; Dissolution ; Oral drug delivery ; Solubility ; Polymeric drug carrier
• 刊名：International Journal of Pharmaceutics
• 出版年：2012
• 期刊代码：24_03785173
• 类别：pha
• 出版时间：15 June, 2012
• 卷：429
• 期：1-2
• 页码：58-68
• 文件大小：1431 K

摘要

Hot-melt extrusion was applied to improve dissolution behavior of poorly soluble model drug fenofibrate. Blends of polymers were used as carrier: copovidone (COP), polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol copolymer (PVCL-PVAc-PEG) and hypromellose 2910/5 (HPMC). The ratio of fenofibrate to COP remained constantly 1 + 3 (weighted parts) with varying amounts of PVCL-PVAc-PEG and HPMC. Solid state of fenofibrate was characterized by X-ray diffractometry and differential scanning calorimetry. Dissolution performance was compared to marketed formulations Lipidil and Lipidil-Ter. Stability studies were conducted at 25 掳C/60%rH.

The dissolution rate from extrudates was significantly increased when compared to pure fenofibrate powder or physical mixture of the components. A supersaturation of 7.6-12.1 was reached with the pelletized extrudates. All extrudates were superior to marketed formulations. No recrystallization was observed after 26 weeks of storage for fenofibrate-COP extrudates 1 + 3 (weighted parts) with or without polymeric additives. Even so, both degree and duration of supersaturation decreased with increasing storage periods with the exception of fenofibrate-HPMC extrudates.

Of particular interest is the finding that by adding polymers with differing release characteristics to the drug-carrier mixture, the dissolution performance of hot-melt extruded solid dosage forms can be readily adapted to meet specific requirements.