Liquisolid pellets: A pharmaceutical technology strategy to improve the dissolution rate of ritonavir

摘要

Liquisolid pellets (LPs) prepared by extrusion-spheronization are promising delivery systems to improve the dissolution rate of poorly water-soluble drugs. However, developing LPs for high dose drugs (e.g. antiretroviral ritonavir, RTV) is a major challenge due to technical and quality constraints. In this study, formulations LP1 and LP2 were obtained (RTV 100?mg/unit dose) using microcrystalline cellulose (carrier), Kollidon? CL-SF (coating and disintegrating material) and high load (30%, w/w) of Kolliphor? EL or PEG 400 (non-volatile solvent). LP1 and LP2 had narrow size distribution, good morphological properties, and excellent flowability. The partial conversion of RTV polymorph I to the less soluble form II occurred during the preparation of the liquid medications. LP1 (containing Kolliphor? EL) achieved 82.64?±?2.17% of drug dissolved in 30?min (Qsub30min/sub), compared with 53.14?±?0.6% and 42.42?±?2.09% for LP2 (containing PEG 400) and Norvir? tablets, respectively. Also, LP1 promoted 1.9-fold/1.7-fold and 8.19-fold/8.29-fold increases in Qsub30min/sub/DEsub60min/sub (dissolution efficiency) as compared to neat RTV polymorphs I and II, respectively.