title: Chitosan-based controlled porosity osmotic pump for colon-specific delivery system: screening of formulation variables and in vitro investigation.
abstract: A microbially triggered colon-targeted osmotic pump (MTCT-OP) has been studied. The gelable property at acid condition and colon-specific biodegradation of chitosan were used to: (1) produce the osmotic pressure, (2) form the drug suspension and (3) form the in situ delivery pores for colon-specific drug release, respectively. The scanning electron microscopy (SEM) study and the calculation of membrane permeability were applied to elucidate the mechanism of MTCT-OP. The effects of different formulation variables, including the level of pH-regulating excipient (citric acid) and the amount of chitosan in the core, the weight gain of semipermeable membrane and enteric-coating membrane, and the level of pore former (chitosan) in the semipermeable membrane, have been studied. Results of SEM showed that the in situ delivery pores could be formed in predetermined time after coming into contact with dissolution medium, and the number of pore was dependent on the initial level of pore former in the membrane. The amount of budesonide release was directly proportional to the initial level of pore former, but inversely related to the weight of semipermeable membrane. The effects of variations in the level of citric acid and chitosan in the core formulation on drug release were studied. The different levels of enteric-coating membrane could prevent cellulose acetate membrane (containing chitosan as pore former) from forming pore or rupture before contact with simulated colonic fluid, but had no effect on the drug release. Budesonide release from the developed formulation was inversely proportional to the osmotic pressure of the release medium, confirming that osmotic pumping was the major mechanism of drug release. These results showed that MTCT-OP based on osmotic technology and microbially triggered mechanism had a high potential for colon-specific drug delivery.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, P.O. Box 122, Shenyang 110016, PR China.
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Xing-Gang
authors.initials: XG
authors.lastname: Yang
authors.forename: Shu-Fang
authors.initials: SF
authors.lastname: Nie
authors.forename: Lan-Lan
authors.initials: LL
authors.lastname: Wei
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Zhou
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Ren
authors.initials: R
authors.lastname: Tang
authors.forename: Wei-San
authors.initials: WS
authors.lastname: Pan
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry; D001419:Bacteria / Q000378:metabolism*; D019819:Budesonide / Q000737:chemistry; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry* / Q000378:metabolism; D019343:Citric Acid / Q000737:chemistry; D003106:Colon / Q000378:metabolism / Q000382:microbiology*; D004337:Drug Carriers; D004339:Drug Compounding; D005079:Excipients / Q000737:chemistry; D005782:Gels; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008567:Membranes, Artificial; D008956:Models, Chemical; D009997:Osmotic Pressure; D010539:Permeability; D016062:Porosity; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013608:Tablets, Enteric-Coated; D014783:Viscosity
chemical_list: D000893:Anti-Inflammatory Agents; D004337:Drug Carriers; D005079:Excipients; D005782:Gels; D008567:Membranes, Artificial; D013608:Tablets, Enteric-Coated; D019343:Citric Acid; C005062:acetylcellulose; D019819:Budesonide; D002482:Cellulose; D048271:Chitosan