Development of a poloxamer analogs/carbopol-based in situ gelling and mucoadhesive ophthalmic delivery system for puerarin.
Conventional ophthalmic solutions often eliminate rapidly after administration and cannot provide and maintain an adequate concentration of the drug in the precorneal area. To solve these problems, we developed a thermosensitive in situ gelling and mucoadhesive ophthalmic drug delivery system containing puerarin based on poloxamer analogs (21% (w/v) poloxamer 407/5% (w/v) poloxamer 188) and carbopol (0.1% (w/v) or 0.2% (w/v) carbopol 1342P NF). The combined solutions would convert to firm gels under physiological condition and attach to the ocular mucosal surface for a relative long time. The incorporation of carbopol 1342P NF not only did not affect the pseudoplastic behavior with hysteresis of the poloxamer analogs solution and led to a higher shear stress at each shear rate, but also enhanced the mucoadhesive force significantly. In vitro release studies demonstrated diffusion-controlled release of puerarin from the combined solutions over a period of 8h. In vivo evaluation (the elimination of puerarin in tear and intraocular pressure-lowering effect) indicated the combined solutions had better ability to retain drug than poloxamer analogs or carbopol alone. It appears that ocular bioavailability can be increased more readily by using the in situ gelling and mucoadhesive vehicle.
Qi
Hongyi
H
School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Shi'er qiao Road 37, Chengdu 610075, PR China.
Chen
Wenwen
W
Huang
Chunyan
C
Li
Li
L
Chen
Chuming
C
Li
Wenmin
W
Wu
Chunjie
C
D000180:Acrylic Resins; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D003692:Delayed-Action Preparations; D004058:Diffusion; D004337:Drug Carriers; D004339:Drug Compounding; D005123:Eye / Q000378:metabolism*; D005782:Gels; D007429:Intraocular Pressure / Q000187:drug effects; D007529:Isoflavones / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D009092:Mucous Membrane / Q000378:metabolism; D009883:Ophthalmic Solutions; D020442:Poloxamer / Q000737:chemistry* / Q000378:metabolism; D011145:Polyvinyls / Q000737:chemistry* / Q000378:metabolism; D011817:Rabbits; D012212:Rheology; D033081:Shear Strength; D012995:Solubility; D013666:Tears / Q000378:metabolism; D013696:Temperature; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D014783:Viscosity
D000180:Acrylic Resins; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005782:Gels; D007529:Isoflavones; D009883:Ophthalmic Solutions; D011145:Polyvinyls; D014665:Vasodilator Agents; C006912:carboxypolymethylene; D020442:Poloxamer; C033607:puerarin