Development of dorzolamide hydrochloride in situ gel nanoemulsion for ocular delivery.
BACKGROUND
Several in situ gel-forming systems have been developed to prolong the precorneal residence time of a drug and to improve ocular bioavailability. Poloxamer 407 with its thermoreversible gelation and surface active properties was utilized to formulate a novel dorzolamide hydrochloride in situ gel nanoemulsion (NE) delivery system for ocular use.


OBJECTIVE
Improvement of both ocular bioavailability and duration of action for dorzolamide hydrochloride was the aim of this study.


METHODS
Physicochemical properties, in vitro drug release studies and biological evaluation of the prepared NEs were investigated.


RESULTS
The optimum formulation of in situ gel NE consisted of Triacetin (7.80%), Poloxamer 407 (13.65%), Poloxamer 188 (3.41%), Miranol C2M (4.55%), and water (70.59%). Biological evaluation of the designed dorzolamide formulation on normotensive albino rabbits indicated that this formulation had better biological performance, faster onset of action, and prolonged effect relative to either drug solution or the market product. The formula showed a superior pharmacodynamic activity compared to the in situ gel dorzolamide eye drops. This indicated the effectiveness of the in situ gel properties of poloxamer 407, besides formulating the drug in an NE form for improving the therapeutic efficacy of the drug.


CONCLUSIONS
These results demonstrate the superiority of in situ gel NE to conventional ocular eye drops and in situ gels to enhance ocular drug bioavailability.
Ammar
H O
HO
Department of Pharmaceutical Technology, National Research Centre Dokki, Cairo, Egypt. husseinammar@hotmail.com
Salama
H A
HA
Ghorab
M
M
Mahmoud
A A
AA
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001682:Biological Availability; D003692:Delayed-Action Preparations; D004655:Emulsions; D005079:Excipients / Q000737:chemistry*; D005123:Eye / Q000378:metabolism; D005782:Gels; D008297:Male; D053758:Nanoparticles; D020442:Poloxamer / Q000737:chemistry*; D011817:Rabbits; D013449:Sulfonamides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013501:Surface-Active Agents / Q000737:chemistry; D013876:Thiophenes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013997:Time Factors
D000959:Antihypertensive Agents; D003692:Delayed-Action Preparations; D004655:Emulsions; D005079:Excipients; D005782:Gels; D013449:Sulfonamides; D013501:Surface-Active Agents; D013876:Thiophenes; D020442:Poloxamer; C062765:dorzolamide