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.