A redispersible dry emulsion system with simvastatin prepared via fluid bed layering as a means of dissolution enhancement of a lipophilic drug

摘要

The purpose of the study was to develop a redispersible dry emulsion, containing a lipophilic, poorly water soluble model drug simvastatin, by employing fluid bed coating technology. The presented dry emulsion manufacturing approach produces pellets in a way, where a layer of the dry emulsion is applied to a neutral core. In the preliminary formulation development phase 1-oleoyl-rac-glycerol was chosen as the oily lipid phase, based on the high drug solubility and potential bioavailability enhancement capability. Mannitol, HPMC and Tween 20 were selected as the solid carriers and surfactant, respectively. The design of experiments, specifically the mixture design approach, was used to obtain the optimal formulation composition. The emulsion reconstitution ability and stability were the main responses, used as the decisive parameters for formulation optimisation. Optimised formulations showed narrow droplet size distribution upon reconstitution, high stability, suitable drug loading and enhanced dissolution profile, compared to a non-lipid based tablet and the pure drug. The scanning electron microscopy, Raman spectroscopy and image analysis disclosed a uniform morphology of the applied layer with separated droplets with simvastatin and uniform size distribution and a circular shape of coated pellets. The study represents the proof of concept of designing redispersible dry emulsions using a fluid bed layering approach.