Nonionic surfactant structure on the drug release, formulation and physical properties of ethylcellulose microspheres

摘要

ABSTRACT Evaluate the effects of nonionic surfactants Brij 58 and Tween 40 with different structures but similar hydrophilic lipophilic balances (HLBs) on theophylline (TH)-loaded ethylcellulose (EC) microspheres. Microspheres were formulated using ratios of the surfactants with matching HLB values but different chemical-structures at temperatures (22/35 °C) by hydrophobic solvent-emulsion evaporation. Particle size, GMD, drug loading, encapsulation efficiency and dissolution were evaluated. Drug release was determined using the zero- and first-order, Higuchi and Hixson-Crowell models. EC microspheres prepared with surfactant Brij 58 showed discrete, free-flowing spherical particles, solid interiors and increased particle smoothness as temperature increased; those prepared with Tween 40 appeared porous with coarser surface morphology as temperature increased; both were CHLB (Combined HLB) dependent. Dissolution obeyed the Higuchi model drug release for both microspheres prepared with Tween 40 and Brij 58 except for those prepared with Brij 58 at 35 °C, which presented as zero order. The results were ascribed to the different chemical structure of Brij 58 versus Tween 40 and preparation temperature. Surfactant chemical structure is an unreported processing parameter shown here to be important in microsphere formulation. Brij 58 possesses properties unique to its chemical structure that influence pharmaceutical and molecular biopharmaceutical research.