Influences of osmotic agents in diffusion layer on drug release from multilayer coated pellets.
Nonpareil beads were coated with three different functional layers, namely inner chlorpheniramine maleate-loaded hydroxypropylmethylcellulose (HPMC, 4 mPa x s) deposition layer, middle HPMC (400 mPa x s) diffusion layer, and outer polyacrylic polymer (Eudragit RS30D) retention layer. The osmotic agents, including sodium chloride, glycine, citric acid, and disodium hydrogen phosphate, were incorporated in different amounts into the diffusion layer and the influences on drug release were studied. The osmotic agent competed with HPMC for imbibed water and subsequently caused more water influx owing to the osmotic pressure gradient. An appropriate amount of osmotic agent in the diffusion layer was necessary to exert its effect on retarding drug release. The osmotic effect on drug release was compromised with pellets at a higher coating level of the diffusion layer due to the extensive swelling and rupture of coat. The release parameters, including dissolution T50% and mean dissolution time, showed linear relationship with osmolalities of osmotic agents studied. The effect of the osmotic agent in the diffusion layer played an important role in determining the unique multiphase drug release profiles, particularly in the initial phase of dissolution, and reduced with depletion of the osmotic agent in the later phase of dissolution.
Heng
Paul Wan Sia
PW
Department of Pharmacy, National University of Singapore, Singapore. phapaulh@nus.edu.sg
Hao
Jinsong
J
Chan
Lai Wah
LW
Chew
Siok Hui
SH
D000180:Acrylic Resins / Q000737:chemistry; D000277:Adjuvants, Pharmaceutic / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D002744:Chlorpheniramine / Q000008:administration & dosage / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000737:chemistry*; D004058:Diffusion; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D008863:Microspheres; D009994:Osmolar Concentration; D009997:Osmotic Pressure; D012995:Solubility; D014783:Viscosity
D000180:Acrylic Resins; D000277:Adjuvants, Pharmaceutic; D003692:Delayed-Action Preparations; C050528:Eudragit RS; D065347:Hypromellose Derivatives; D002744:Chlorpheniramine; D008747:Methylcellulose