Fast release of liquid antisolvent precipitated fenofibrate at high drug loading from biocompatible thin films

摘要

Motivated by recent papers on nano and micro-particle slurry casting of poorly water-soluble drugs forming biocompatible films with enhanced properties, this work explores incorporation of liquid antisolvent (LAS) precipitated suspensions of fenofibrate, a model poorly soluble drug using both semi-synthetic (HPMC E15 LV) and natural (sodium alginate, SA) polymer as film formers. Centrifugation and subsequent resuspension were employed to minimize residual solvent and increase drug loading (～20%) in the LAS suspensions and in the film. Film’s critical quality attributes (CQAs), including drug distribution and uniformity, mechanical properties, and dissolution were assessed. Crystalline nature of FNB was largely preserved in the film without any polymorphic changes confirmed by XRD, DSC, and Raman. The NIR chemical imaging, corroborated by SEM imaging and drug content relative standard deviation (RSD) indicates that the drug is uniformly distributed without any observable large agglomerates. The films with SA showed lower mechanical strength as compared to HPMC due to SA’s low molecular weight. All films exhibited immediate drug release as has been the case using FNB nano particles in previous papers. Interestingly, although addition of plasticizer improved film dissolution, HPMC-based films had a faster dissolution compared to SA-based films in spite of higher mechanical strength of the former.