(443c) Critical Material Attributes (CMAs) of Strip Films Loaded with Poorly Water-Soluble Drug Particles: IV. Surface-Modified Dry Micronized Drug Powders

Recent work has established polymer strip films as a robust platform for delivery of poorly water-soluble drug using their nanosuspensions. However, a simpler means of incorporating drug particles has yet to be demonstrated. Consequently, the feasibility of incorporating micronized fenofibrate (FNB), a model poorly water-soluble drug, via simultaneous micronization and surface modification with hydrophilic silica using fluid energy mill (FEM) was investigated. Milled silica coated FNB (MC-FNB) was prepared to faciliate direct incorporation into aqueous film precursor made using hydroxypropyl methylcellulose (HPMC-E15LV) as film former and glycerin as plasticizer. Films with as-received FNB (AR-FNB) and milled/uncoated FNB (MU-FNB) were prepared as control. The impacts of film precursor viscosity, low versus high shear mixers, and FNB surface modification on critical quality attributes (CQAs) of film product were assessed. Generally, high-shear planetary mixer resulted in better film CQAs; e.g., appearance (thickness uniformity, visible lumps/agglomerates), drug content uniformity (RSD%), and mechanical properties (ultimate tensile strength, elongation percentage, Young’s modulus). Use of MC-FNB particles was necessary to achieve superior film CQAs when commonly used lower-shear impellor mixing and low film precursor viscosity were used. The well dispersed hydrophilic silica particles conveyed a nano-scale surface roughness and helped to increase the wettability of poorly water soluble drug, which lead to a significant reduction in the tendency to form agglomerates and also had a positive effect on the dissolution of drug powders. Importantly, use of MC-FNB led to improved drug particle size recovery upon redispersion and fast, complete drug release. The results demonstrate feasibility and advantages of direct incorporation of dry surface modified-micronized poorly water-soluble drug powders in film manufacturing.