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

作者：Kalivoda Adela; Fischbach Matthias; Kleinebudde Peter^*

来源：International Journal of Pharmaceutics, 2012, 429(1-2): 58-68.

DOI：10.1016/j.ijpharm.2012.03.009

• Solid dispersion
• Hot-melt extrusion
• Fenofibrate
• Dissolution
• Oral drug delivery
• Solubility
• Polymeric drug carrier

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 degrees C/60%rH. %26lt;br%26gt;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. %26lt;br%26gt;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.

• 出版日期2012-6-15