Influence of plasticization time, curing conditions, storage time, and core properties on the drug release from Aquacoat-coated pellets.
Theophylline or chlorpheniramine maleate pellets were coated with an aqueous ethylcellulose dispersion, Aquacoat. The influence of the plasticization time, curing conditions, storage time, and core properties on the drug release were investigated. The plasticization time (time between plasticizer addition to the polymer dispersion and the spraying process) did not affect the drug release, when the water-soluble plasticizer triethyl citrate, was used because of its rapid uptake by the colloidal polymer particles. In contrast, with the water-insoluble plasticizer acetyltributyl citrate (ATBC), plasticization time (1/2 h vs 24 h) influenced the drug release, the longer plasticization time resulted in a slower drug release because of a more complete plasticizer uptake prior to the coating step. However a thermal aftertreatment of the coated pellets at eleylated temperatures (curing step) reduced/eliminated the effect of the plasticization time with ATBC. In general, curing reduced the drug release and resulted in stable drug release profiles. The time period between the coating and the curing step was not critical when the pellets were cured for a longer time. The structure of the pellet core (high dose matrix vs low dose layered pellet) strongly affected the drug release. A slow, zero-order drug release was obtained with high dose theophylline pellets, while a more rapid, first-order release pattern was obtained with low dose theophylline-layered nonpareil pellets.
Wesseling
M
M
College of Pharmacy Freie Universität Berlin, Berlin, Germany.
Bodmeier
R
R
D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry*; D002744:Chlorpheniramine / Q000737:chemistry; D002951:Citrates / Q000737:chemistry; D003102:Colloids; D003692:Delayed-Action Preparations / Q000737:chemistry; D004343:Drug Implants / Q000737:chemistry; D004356:Drug Storage / Q000379:methods; D005079:Excipients; D006634:Histamine H1 Antagonists / Q000737:chemistry; D010726:Phosphodiesterase Inhibitors / Q000737:chemistry; D010968:Plasticizers / Q000737:chemistry*; D013806:Theophylline / Q000737:chemistry
D002951:Citrates; D003102:Colloids; D003692:Delayed-Action Preparations; D004343:Drug Implants; D005079:Excipients; D006634:Histamine H1 Antagonists; D010726:Phosphodiesterase Inhibitors; D010968:Plasticizers; C014953:2-acetyltributylcitrate; D002744:Chlorpheniramine; C013517:ethyl cellulose; C023001:ethyl citrate; D002482:Cellulose; D013806:Theophylline