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

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 °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.

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