Controlling the structure of spin-coated multilayer ethylcellulose/ hydroxypropylcellulose films for drug release

• Porous phase-separated ethylcellulose/hydroxypropylcellulose (EC/HPC) films are used to control drug transport out of pharmaceutical pellets. Water-soluble HPC leaches out and forms a porous structure that controls the drug transport. Industrially, the pellets are coated using a fluidized bed spraying device, and a layered film exhibiting varying porosity and structure after leaching is obtained. A detailed understanding of the formation of the multilayered, phase-separated structure during production is lacking. Here, we have investigated multilayered EC/HPC films produced by sequential spin-coating, which was used to mimic the industrial process. The effects of EC/HPC ratio and spin speed on the multilayer film formation and structure were investigated using advanced microscopy techniques and image analysis. Cahn-Hilliard simulations were performed to analyze the mixing behavior. A gradient with larger structures close to the substrate surface and smaller structures close to the air surface was formed due to coarsening of the layers already coated during successive deposition cycles. The porosity of the multilayer film was found to vary with both EC/HPC ratio and spin speed. Simulation of the mixing behavior and in situ characterization of the structure evolution showed that the origin of the discontinuities and multilayer structure can be explained by the non-mixing of the layers.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

NATURVETENSKAP  -- Kemi (hsv//swe)

NATURAL SCIENCES  -- Chemical Sciences (hsv//eng)

LANTBRUKSVETENSKAPER  -- Lantbruksvetenskap, skogsbruk och fiske -- Livsmedelsvetenskap (hsv//swe)

AGRICULTURAL SCIENCES  -- Agriculture, Forestry and Fisheries -- Food Science (hsv//eng)

Nyckelord

Cahn -Hilliard simulations

Cellulose

Confocal laser scanning

microscope

Electron microscopy

Multilayer film

Phase separation

kinetics

Phase separation mechanisms

Porous film for controlled

release

modeling solvent evaporation

induced phase-separation

polymer blends

structure evolution

diffusion

Pharmacology & Pharmacy

Confocal laser scanning microscope

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