Effect of water-soluble polymers on the physical stability of aqueous polymeric dispersions and their implications on the drug release from coated pellets

Purpose: To investigate the physical stability and drug release-related properties of the aqueous polymer dispersions Kollicoat (R) SR 30 D and Aquacoat (R) ECD (an ethylcellulose-based dispersion) in the presence water-soluble polymers (pore formers) with special attention to the potential flocculation of the polymer dispersions. Methods: A precise characterization of the flocculation phenomena in undiluted samples was monitored with turbidimetric measurements using the Turbiscan Lab-Expert. Theophylline or propranolol HCl drug-layered pellets were coated with Kollicoat (R) SR 30 D and Aquacoat (R) ECD by the addition of water-soluble polymers polyvinyl pyrrolidone (Kollidon (R) 30 and 90 F), polyvinyl alcohol-polyethylene glycol graft copolymer (Kollicoat (R) IR), and hydroxypropyl methylcellulose (Pharmacoat (R) 603 or 606) in a fluidized bed coater Glatt GPCG-1 and drug release was performed according to UPS paddle method. Results: Stable dispersions were obtained with both Kollicoat (R) SR 30 D (a polyvinyl acetate-based dispersion) and Aquacoat (R) ECD with up to 50% hydrophilic pore formers polyvinyl alcohol-polyethylene glycol graft copolymer (Kollicoat (R) IR) and polyvinyl pyrrolidone (Kollidon (R) 30). In general, Kollicoat (R) SR 30 D was more stable against flocculation than Aquacoat (R) ECD. Stable dispersions were also obtained with higher amounts of water-soluble polymer or by reducing the concentration of the polymer dispersion. Flocculated dispersions resulted in porous films and, thus, in a sharp increase in drug release. Conclusions: Kollicoat (R) SR 30 D was more resistant to flocculation upon addition of water-soluble polymers than Aquacoat (R) ECD. The continuous adjustment of drug release from Kollicoat (R) SR 30-coated pellets was possible with Kollicoat (R) IR amounts over a broad range.