Supercritical Phase Inversion To Form Drug-Loaded Poly(vinylidene fluoride-co-hexafluoropropylene) Membranes

Abstract

Membranes loaded with an active principle are one of the alternatives proposed to obtain controlled release pharmaceutical formulations. Until now, several methods have been proposed for the fabrication of membranes as drug delivery devices, such as phase inversion, gas foaming/particulate leaching, and solvent evaporation. Supercritical CO2 (SC-CO2) phase inversion offers an alternative process to obtain solvent-free membranes with short processing times, avoiding the collapse of the structure. We prepared poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF−HFP) loaded membranes by SC-CO2 phase inversion, performing experiments at pressures ranging between 150 and 250 bar and at temperatures ranging between 35 and 55 °C. We selected as the base case the PVDF−HFP−acetone solution at 15% w/w polymer and modified the drug (amoxicillin) concentration from 20 to 50% w/w with respect to PVDF−HFP. Different membranes morphologies, ranging from nanometric gel-like networks (mean pores diameter of about 150 nm) to micrometric cellular structures (mean cells diameter ranging between 5 and 12 μm), and different drug distributions were obtained, depending on the process conditions. Drug-controlled release experiments were also performed to study the kinetics and duration of the release process.

Effect of solvents on morphology and polymorphism of polyvinylidene fluoride membrane via supercritical CO2 induced phase separation

“…Because of the absence of a liquid-vapor interface, porous membranes can be prepared without collapse of structure; supercritical CO 2 not only induce phase separation but also dry the formed membrane meanwhile; the organic solvent dissolved in supercritical CO 2 allows to be extremely removed by simply diminishing the pressure. 12 Generally speaking, polymer crystallinity and the resultant membrane morphology are among important factors in determining the physical and chemical properties of membrane. It is widely accepted that, PVDF chains can crystallize into at least four distinct phases or forms, which are a (form II), b (form I), c (form III), and d (form IV).…”

Supercritical fluids applications in nanomedicine

“…A c c e p t e d M a n u s c r i p t However, there are several works in the literature on membrane production using SC-induced phase separation, for various applications [132][133][134][135][136][137] and also for biomedical field [138,139]; but, nanostructure in some cases is not present. Tsivintzelis et al [140] prepared porous scaffolds of PLLA, a biocompatible and biodegradable polymer, and investigated the effect of pressure, temperature and initial concentration of the polymer solution on the final structure; but, nanostructure was absent.…”

“…SC-assisted phase separation was also applied for the production of drug carriers; i.e., nanoporous membranes loaded with an active principle. Cardea et al [147] used this process to produce Polyvinylidene fluoride-hexafluoropropylene (PVDF-HFP) membranes loaded with the antibiotic Amoxicillin. The authors observed that when SC-CO 2 solvent power was high, the phase separation was rapid and solid-liquid demixing was obtained, leading to a nanometric structure with a mean pore diameter of about 150 nm.…”

Supercritical CO2 for the Reactive Precipitation of Calcium Carbonate: Uses and Applications to Industrial Processing

“…From the use of carbon dioxide as a drying agent in supercritical fluid drying, to the use of carbon dioxide as a plasticizing agent in gas foaming and sintering or the use of carbon dioxide as an anti-solvent in the supercritical assisted phase inversion method, almost all encounter a way to satisfy most of the characteristics requested. A summary of the features of the different technologies and some examples of drug delivery systems for tissue engineering and regenerative medicine applications are listed in Table 12.3 [78][79][80][81][82][83][84][85][86][87][88]. Hydrogel foaming is a more recent technique which has been explored for the preparation of porous scaffolds and in this process hydrogels foaming involves the dissolution of carbon dioxide in the water phase present on the hydrogel which will promote foaming of the structure upon depressurization [89,90].…”

“…Starch-poly-lactic acid blend impregnated with dexamethasone [84] Poly(vinylidene fluoride-cohexafluoropropylene) loaded with amoxicillin [85] Poly-methylmethacrylate loaded with amoxicilin [86]…”