title: Thermosensitive and mucoadhesive in situ gel based on poloxamer as new carrier for rectal administration of nimesulide.
abstract: Poloxamer 407 has excellent thermo-sensitive gelling properties. Nevertheless, these gels possess inadequate poor bioadhesiveness and high permeability to water, which limited its' application as a thermoresponsive matrix. The main aim of the present investigation was to develop thermosensitive and mucoadhesive rectal in situ gel of nimesulide (NM) by using mucoadhesive polymers such as sodium alginate (Alg-Na) and HPMC. These gels were prepared by addition of mucoadhesive polymers (0.5%) to the formulations of thermosensitive gelling solution containing poloxamer 407 (18%) and nimesulide (2.0%). Polyethylene glycol (PEG) was used to modify gelation temperature and drug release properties. The gelation temperature and drug release rate of the prepared in situ gels were evaluated. Gelation temperature was significantly increased with incorporation of nimesulide (2.0%) in the poloxamer solution, while the addition of the mucoadhesive polymers played a reverse role on gelation temperature. The addition of PEG polymers increased the gelation temperature and the drug release rate. Among the formulations examined, the poloxamer 407/nimesulide/sodium alginate/PEG 4000 (18/2.0/0.5/1.2%) exhibited the appropriate gelation temperature, acceptable drug release rate and rectal retention at the administration site. Furthermore, the micrographic results showed that in situ gel, given at the dose of 20mg/kg, was safe for no mucosa irritation. In addition, it resulted in significantly higher initial serum concentrations, C(max) and AUC of NM compared to the solid suppository.
authors.affiliation: Department of Pharmacy, Logistic University of Chinese People's Armed Police Forces, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.forename: Ying
authors.initials: Y
authors.lastname: Cui
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Hui-Ping
authors.initials: HP
authors.lastname: Zhu
authors.forename: Yi-Sha
authors.initials: YS
authors.lastname: Guo
authors.forename: Bo
authors.initials: B
authors.lastname: Zhong
authors.forename: Xia
authors.initials: X
authors.lastname: Hu
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Chen
mesh_terms: D000268:Adhesiveness; D000285:Administration, Rectal; D000464:Alginates / Q000737:chemistry; D000818:Animals; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers; D004339:Drug Compounding; D005782:Gels; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D008297:Male; D009092:Mucous Membrane / Q000378:metabolism; D020442:Poloxamer / Q000737:chemistry / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry; D011817:Rabbits; D012007:Rectum / Q000378:metabolism*; D012995:Solubility; D013449:Sulfonamides / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D013678:Technology, Pharmaceutical / Q000379:methods; D044366:Transition Temperature
chemical_list: D000464:Alginates; D052246:Cyclooxygenase 2 Inhibitors; D004337:Drug Carriers; D005782:Gels; D006603:Hexuronic Acids; D013449:Sulfonamides; D020442:Poloxamer; D011092:Polyethylene Glycols; D020723:Glucuronic Acid; C012655:nimesulide