[Preparation and in vitro corneal retention behavior of novel cationic microemulsion/in situ gel system].
The aim was to prepare a novel ocular cationic microemulsion-in situ gel (CM-ISG) system with vitamin A palmitate (VAP) as model drug, and investigate the corneal retention behavior and corneal irritation of the system. VAP/CM was prepared by a process based on supply of energy, and the before-and-after gelation rheology of VAP/CM-ISG was investigated. In vitro VAP release and gel dissolution of both VAP/CM-ISG and Oculotect Gel was determined. And in vitro corneal retention behavior of both formulations was evaluated by captive bubble technique. Ocular irritation test was carried out based on the Draize method. Images of TEM showed that homogenous VAP/CM was made, and no significant differences of particle size were found between the VAP/CM and VAP/CM in Poloxamer 407 gel. Rheology study illustrated that VAP/CM reduced the phase transition temperature of Poloxamer 407 gel by 1.5 degrees C, and the elastic modulus increased about 15.7 times. The in vitro release and gel dissolution profile of both formulations exhibited the characteristics of zero order kinetics. Comparing with Oculotect Gel, desorption kinetics study of VAP/CM-ISG exhibited longer corneal retention time and smaller contact angle. Irritation test showed a good ocular compatibility of VAP/CM-ISG. Therefore, VAP/CM-ISG combined both advantages of the cationic microemulsion and in situ gel system, provided better wettability and longer ocular retention time. It might be a promising ocular drug delivery system.
Ma
Shou-wei
SW
China Pharmaceutical University, Nanjing 210009, China.
Gan
Yong
Y
Gan
Li
L
Zhu
Chun-liu
CL
Zhu
Jia-bi
JB
D000818:Animals; D003315:Cornea / Q000187:drug effects / Q000378:metabolism*; D003692:Delayed-Action Preparations; D004224:Diterpenes; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004655:Emulsions; D009883:Ophthalmic Solutions; D020442:Poloxamer / Q000737:chemistry; D011817:Rabbits; D011897:Random Allocation; D000084562:Retinyl Esters; D014783:Viscosity; D014801:Vitamin A / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity
D003692:Delayed-Action Preparations; D004224:Diterpenes; D004337:Drug Carriers; D004655:Emulsions; D009883:Ophthalmic Solutions; D000084562:Retinyl Esters; D020442:Poloxamer; D014801:Vitamin A; C014794:retinol palmitate