Safety and robustness of coated pellets: self-healing film properties and storage stability.
OBJECTIVE
Aim of the study was to verify the safety of chlorpheniramine maleate pellets, coated with blends of poly(vinyl acetate) and poly(vinyl alcohol)-poly(ethylene glycol) graft copolymer. Therefore, the impact of mechanical forces and storage conditions on the drug release was investigated.


RESULTS
Similar release profiles before and after compression of the pellets to tablets underlined the high film robustness. A damage of the film coat with a razor blade resulted in a premature release, but without a burst. After a similar damage with a needle, the release profile remained almost unchanged, which indicated a swelling based self repair mechanism of the film. Additional studies were dedicated to the storage stability at three different conditions. A slightly delayed release was obtained after 6 months storage at 25 degrees C and a marginally accelerated release was measured after storage at elevated temperatures. No drug migration into the coating layer was detected during storage by confocal Raman microscopy. (1)H-NMR analysis during storage demonstrated, that no polymer or drug degradation had occurred and the plasticizer concentration remained constant.


CONCLUSIONS
The polyvinyl based coating blend for modified release pellets demonstrated a high safety, due to their high robustness and compressibility as well as their satisfying storage stability.
Ensslin
Simon
S
Technical Research & Development, Novartis Pharma AG, Basel, Switzerland.
Moll
Klaus Peter
KP
Haefele-Racin
Thomas
T
Mäder
Karsten
K
D018926:Anti-Allergic Agents / Q000032:analysis* / Q000737:chemistry; D002744:Chlorpheniramine / Q000032:analysis* / Q000737:chemistry; D004355:Drug Stability; D004356:Drug Storage; D006244:Hardness; D011092:Polyethylene Glycols / Q000032:analysis* / Q000737:chemistry; D011142:Polyvinyl Alcohol / Q000032:analysis* / Q000737:chemistry; D011145:Polyvinyls / Q000032:analysis* / Q000737:chemistry; D012995:Solubility; D013499:Surface Properties; D013607:Tablets / Q000737:chemistry*; D013696:Temperature
D018926:Anti-Allergic Agents; D011145:Polyvinyls; D013607:Tablets; C013215:polyvinyl acetate; D002744:Chlorpheniramine; D011092:Polyethylene Glycols; D011142:Polyvinyl Alcohol