(197g) Physicochemical Properties of Biocompatible Films Containing Concentrated Fenofibrate Particles Prepared Via Liquid Antisolvent Precipitation

Approximately 40% of newly discovered molecules are poorly water-soluble and this class of drugs lacks a formulation strategy capable of producing high loads, fast dissolution rates. Biocompatible films have great potential over other dosage forms for delivery of poorly soluble drugs as they provide distinct advantages such as: easy to swallow, convenient for geriatric and pediatric patients, larger surface area which leads to rapid disintegration and dissolution in the oral cavity and increased bioavailability. In this study, we developed biocompatible strip films by incorporating concentrated suspension of fenofibrate (FNB), a model poorly water-soluble compound, produced by liquid antisolvent (LAS) precipitation. Stabilization of the suspension was established via combination of non-ionic surfactant Pluronic F68 and the polymer hydroxypropyl methyl cellulose (HPMC E3). Centrifugation and subsequent resuspension was used to concentrate suspensions and minimize residual solvent level. The resulting micro suspensions were then formulated with high viscous cellulosic polymer solution of HPMC (E15 LV), anionic polysaccharide of sodium alginate (NaAlg), and a combination of both to make biocompatible film. Glycerin was used as plasticizer and its effect on mechanical strength, dissolution was investigated. The morphology of the drug particles from suspensions and the structure of the films were observed by using scanning electron microscopy (SEM). The crystallinity of drug particles in films was studied by X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Raman spectroscopy. Distribution of drug particles in the films was studied by NIR chemical imaging. The influence of the formulations on the filmâ??s mechanical properties was studied. The SEM images show that the films exhibit different morphologies depending on film formulation. The cross-sectional images showed that the films with HPMC or combination of HPMC-NaAlg having glycerin had porous structure which could be due to the presence of glycerin that modified the tertiary structure of polymer into porous structure. The NIR chemical imaging indicates that the drug is uniformly distributed without any observable large agglomerates. XRD, DSC and Raman results suggest that the crystalline nature of FNB was largely preserved after film formation and no polymorphic change has occurred. A substantial decrease in Youngâ??s modulus and tensile strength are observed for film having NaAlg. The drug release profiles for all of the formulated films showed clear distinction between the films and as-received FNB powder. The addition of plasticizer, i.e., glycerin, decreased dissolution time of film containing HPMC as compared to un-plasticized film. The fastest drug release was achieved from film which contained HPMC or combination of HPMC-NaAlg having glycerin. The decreased dissolution time for HPMC film is probably due to increased film hydrophilicity causes by the presence of glycerin. The films with NaAlg and HPMC as the matrix former were extremely weak, which aids in quick disintegration and dissolution of the film. The porous network of both films was beneficial to quick penetration of the dissolution medium resulting in quick drug release. Our study has demonstrated that high drug loaded biocompatible film can be prepared with LAS precipitated drug suspensions and that film properties can be modulated by formulating with NaAlg.

Keywords: Liquid Antisolvent Precipitation, Stabilizer, Biocompatible Film, Sodium Alginate, Fast Dissolution.