In situ self assembly of soft diclofenac loaded microparticles in superstructured fluids

This study investigated how the in situ construction and payload delivery from soft diclofenac loaded hydroxypropylmethylcellulose (HPMC) coated microparticles was influenced by the superstructure of the cosolvent in which the particles were suspended. A dual nozzle spray was used to produce microparticles in a propylene glycol (PG)–water mixture and data generated from the structural features of the vehicle, the physical properties of the particles and drug transport from the suspensions were used to characterise the particle–vehicle interactions. Infrared spectroscopy indicated supramolecular structures were formed in the bulk PG–water cosolvent upon mixing, but no solvent structural modification was observed as a consequence of microparticle self-assembly. Forming the microparticles in a premixed cosolvent, i.e., with a preformed superstructure, did not allow the polymer to deposit on the surface of the microparticles. The suspensions that did not contain the HPMC coated microparticles demonstrated a reduced diclofenac transmembrane transport rate (7.9 ± 0.4 μg cm−2 h−1) compared to soft HPMC coated particles (27.7 ± 3.0 μg cm−2 h−1). The HPMC–diclofenac hydrogen bonding interactions observed in the polymer coated material, the increased availability of the diclofenac in the solution state (drug degree of saturation rose from 3.0 ± 0.2 to 11.0 ± 1.2) and the slower microparticle formation kinetics (>1 order of magnitude) supported the conclusion that the cosolvent supramolecular structuring controlled HPMC deposition at the particle interface. Analysis of the solid material recovered from the suspensions suggested that the cosolvent supramolecular structures could be used to modify the diclofenac solid–liquid equilibrium and generate a complex liquid with an unusually high chemical potential.