Effects of stabilizers on particle redispersion and dissolution from polymer strip films containing liquid antisolvent precipitated griseofulvin particles

In this work, we provide experimental evidence supporting the dual role of stabilizers on controlling growth and agglomeration of formed particles via liquid antisolvent (LAS) process and use this knowledge to demonstrate the feasibility of integrating these engineered particles into fast dissolving edible pharmaceutical strip films (PSF). A T-mixer was used to produce griseofulvin (GF) particles for incorporation into PSF in continuous mode, while the experiments crucial to elucidate the role of stabilizers were conducted in batch system. Stabilization was examined via addition of the non-ionic surfactant Pluronic F127 (PF 127), the polymer hydroxypropyl methyl cellulose (HPMC LV 15) and their combinations. Centrifugation was evaluated as a means to concentrate suspensions and minimize levels of residual solvent, while keeping the produced particles non-agglomerated. Laser diffraction, SEM imaging, Differential scanning calorimetry (DSC), X-ray diffractometry (XRD) and Near-infrared Spectroscopy (NIR) were employed to characterize the particles and strip films. It was observed that the simultaneous evolution of particle growth and agglomeration is controlled if HPMC LV 15 and PF 127 are present before precipitation while only agglomeration is suppressed if added after precipitation. The addition of PF 127 along with HPMC LV 15 to GF suspensions results in controlling initial growth and suppression of agglomeration during downstream processing via synergistic effects. The optimal formulation results in faster and higher extent of dissolution than a poorly stabilized suspension, a film made from the unprocessed drug, a physical mixture or a compact of similar composition. Along with particle size data, cluster size analysis from NIR imaging emphasizes the role of wettability and re-dispersion in the particle dispersion in the film and recoverability of engineered particles to improve bioavailability.

The optimal formulation of stabilizers that provides improved suspension stability also results in faster and higher extent of dissolution than a poorly stabilized suspension, or the unprocessed/pure drug.Figure optionsDownload as PowerPoint slide