Preparation and evaluation of in situ gelling ophthalmic drug delivery system for methazolamide.
OBJECTIVE
In this study, a thermosensitive in situ gelling vehicle was prepared to increase the precorneal resident time and the bioavailability of methazolamide (MTA).


METHODS
Poloxamer analogs were used as the gelling agents, and the in situ gel was obtained by using a cold method. The gelation temperature, rheological properties, in vitro release as well as in vivo evaluation (the elimination of MTA in aqueous humor and intraocular-lowering effect) of the optimized formulations were investigated.


RESULTS
The optimum concentrations of poloxamer analogs for the in situ gel-forming delivery system were 21% (w/w) poloxamer 407 and 10% (w/w) poloxamer P188. This formulation was able to flow freely under nonphysiological conditions and underwent sol-gel transition in the cul-de-sac upon placement into the eye. In vitro release studies demonstrated a diffusion-controlled release of MTA from the poloxamer solutions over a period of 10 hours. In vivo evaluation indicated that the poloxamer solutions had a better ability to retain drug than MTA eyedrops did.


CONCLUSIONS
These results suggested that in situ gelling ophthalmic drug delivery system may hold some promise in ocular MTA delivery.
Qian
Yong
Y
School of Pharmacy, Nanjing Medical University, Nanjing, PR China.
Wang
Fengzhen
F
Li
Rui
R
Zhang
Qing
Q
Xu
Qunwei
Q
D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D001682:Biological Availability; D002257:Carbonic Anhydrase Inhibitors / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D005123:Eye / Q000378:metabolism; D005260:Female; D005782:Gels; D007429:Intraocular Pressure / Q000187:drug effects; D008297:Male; D008704:Methazolamide / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D020442:Poloxamer / Q000737:chemistry*; D011817:Rabbits; D013696:Temperature; D013997:Time Factors
D002257:Carbonic Anhydrase Inhibitors; D003692:Delayed-Action Preparations; D005782:Gels; D020442:Poloxamer; D008704:Methazolamide