Effect of water-soluble polymers on the physical stability of aqueous polymeric dispersions and their implications on the drug release from coated pellets.
OBJECTIVE
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.
Dashevsky
Andrei
A
Freie Universität Berlin, Berlin, Germany. dashevsk@zedat.fu-berlin.de
Ahmed
Abid Riaz
AR
Mota
J
J
Irfan
Muhammad
M
Kolter
Karl
K
Bodmeier
Roland A
RA
D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004343:Drug Implants / Q000737:chemistry*; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D005427:Flocculation; D007700:Kinetics; D009391:Nephelometry and Turbidimetry; D011145:Polyvinyls / Q000737:chemistry*; D011433:Propranolol / Q000737:chemistry; D012995:Solubility; D013806:Theophylline / Q000737:chemistry
D004343:Drug Implants; D005079:Excipients; D011145:Polyvinyls; C013215:polyvinyl acetate; C013517:ethyl cellulose; D002482:Cellulose; D011433:Propranolol; D013806:Theophylline