title: Long-term stability of heat-humidity cured cellulose acetate phthalate coated beads.
abstract: The objective of this study was to investigate the influence of stability storage conditions on the enteric release of heat-humidity cured cellulose acetate phthalate (CAP) coated beads. Theophylline beads were coated with 25 or 35% diethyl phthalate plasticized CAP dispersion (Aquacoat CPD), and cured at a heat-humidity condition (50 degrees C/75% RH) for 24h. The cured beads were then stored in various container/closure systems (open glass containers, sealed glass containers with and without desiccant) and exposed to 40 degrees C/75% RH for 6 months or 25 degrees C/60% RH for 12 months. At accelerated conditions (40 degrees C/75% RH), only beads stored in sealed glass containers with desiccant displayed stable release profiles throughout the exposure period. The beads stored in sealed glass containers without desiccant showed increased theophylline release in acidic media at 2h, and did not maintain enteric resistance at 6 months. The release profiles of beads stored in open containers, directly exposed to 40 degrees C/75% RH, were the least stable. The decrease in enteric protection of the beads stored at these two packaging conditions was correlated to an increased phthalic acid content in the films. At ambient storage conditions (25 degrees C/60% RH), all samples possessed enteric release properties, irrespective of the container/closure system. Beads stored in sealed glass containers with desiccant remained the most stable compared to those at the other two packaging conditions. The results indicated that although humidity significantly contributed to coalescence of CAP coating during the curing process, the optimum packaging condition for the heat-humidity cured CAP coated beads was with desiccant to maintain the chemical stability of the CAP.
authors.affiliation: Sanofi-Synthelabo Research, Malvern, PA, USA.
authors.forename: Jiping
authors.initials: J
authors.lastname: Liu
authors.forename: Robert O
authors.initials: RO
authors.lastname: Williams
mesh_terms: D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry*; D004355:Drug Stability; D004356:Drug Storage; D006358:Hot Temperature; D006813:Humidity; D008863:Microspheres
chemical_list: D002482:Cellulose; C011708:cellulose acetate phthalate