Temperature-responsive, Pluronic-g-poly(acrylic acid) copolymers in situ gels for ophthalmic drug delivery: rheology, in vitro drug release, and in vivo resident property.
To prolong the precorneal resident time and improve ocular bioavailability of the drug, Pluronic-g-poly(acrylic acid) copolymers were studied as a temperature-responsive in situ gelling vehicle for an ophthalmic drug delivery system. The rheological properties and in vitro drug release of Pluronic-g-PAA copolymer gels, as well as the in vivo resident properties of such in situ gel ophthalmic formulations, were investigated. The rheogram and in vitro drug release studies indicated that the drug release rates decreased as acrylic acid/Pluronic molar ratio and copolymer solution concentration increased. It was also shown that the drug concentration had no obvious effect on drug release. The release rates of drug from such copolymer gels were mainly dependent on the gel dissolution. In vivo resident experiments showed the drug resident time and the total resident amount increased by 4-fold and 1.2-fold for in situ gel compared with eye drops. These in vivo experimental results, along with the rheological properties and in vitro drug release studies, demonstrated that in situ gels containing Pluronic-g-PAA copolymer may significantly prolong the drug resident time and thus improve bioavailability. The results showed that the Pluronic-g-PAA copolymer can be a promising in situ gelling vehicle for ophthalmic drug delivery.
Ma
Wen-di
WD
Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, China. ppwwss@163.com
Xu
Hui
H
Nie
Shu-fang
SF
Pan
Wei-san
WS
D000180:Acrylic Resins / Q000737:chemistry*; D000818:Animals; D001682:Biological Availability; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D005260:Female; D005782:Gels; D008297:Male; D009883:Ophthalmic Solutions; D020442:Poloxamer / Q000737:chemistry*; D011817:Rabbits; D012212:Rheology; D012995:Solubility; D013696:Temperature; D014783:Viscosity; D014805:Vitamin B 12 / Q000008:administration & dosage* / Q000737:chemistry
D000180:Acrylic Resins; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005782:Gels; D009883:Ophthalmic Solutions; D020442:Poloxamer; C006903:carbopol 940; D014805:Vitamin B 12