Development of loteprednol etabonate-loaded cationic nanoemulsified in-situ ophthalmic gel for sustained delivery and enhanced ocular bioavailability.
A novel cationic nanoemulsified in-situ ophthalmic gel of loteprednol etabonate (LE) was developed to improve the permeability and retention time of formulations for overall improvement of drug's ocular bioavability. Capryol 90 (oil phase), tween 80 (surfactant) and transcutol P (cosurfactant) was selected as formulation excipients to construct pseudoternary phase diagrams and nanoemulsion region was recognized from diagrams. Spontaneous emulsification method was used to manufacture LE nanoemulsion and it was optimized using 32factorial design by considering the amount of oil and the ratio of surfactant to cosurfactant (Smix) as independent variables and evaluated for various physicochemical properties. Optimized NE was dispersed in Poloxamer 407 and 188 solution to form nanoemulsified sols that were predictable to transform into in-situ gels at corneal temperature. Drug pharmacokinetics of sterilized optimized in situ NE gel, NE-ISG2 [0.69% w/w Capryol 90, 0.99%w/w Smix(3:1), 13% Poloxamer 407, 4% w/w Poloxamer 188] and marketed formulation were assessed in rabbit aqueous humor. The in-situ gels were clear, shear thinning in nature and displayed zero-order drug release kinetics. NE-ISG2 showed the minimum ocular irritation potential and significantly (p < 0.01) higher Cmaxand AUC(0-10 h), delayed Tmax, extended mean residence time and improved (2.54-fold times) bioavailability compared to marketed formulation.
a Department of Pharmaceutical Sciences , Saurashtra University , Rajkot , Gujarat , India.
Nirav
N
Patel
a Department of Pharmaceutical Sciences , Saurashtra University , Rajkot , Gujarat , India.
Happy
H
Nakrani
a Department of Pharmaceutical Sciences , Saurashtra University , Rajkot , Gujarat , India.
Mihir
M
Raval
a Department of Pharmaceutical Sciences , Saurashtra University , Rajkot , Gujarat , India.
Navin
N
Sheth
D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D001682:Biological Availability; D002412:Cations / Q000008:administration & dosage / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003315:Cornea / Q000378:metabolism; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry; D045703:Emulsifying Agents / Q000737:chemistry; D004655:Emulsions / Q000008:administration & dosage / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry; D005782:Gels / Q000008:administration & dosage / Q000737:chemistry*; D000069559:Loteprednol Etabonate / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D009883:Ophthalmic Solutions / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D010539:Permeability; D011817:Rabbits; D013501:Surface-Active Agents / Q000737:chemistry
D002412:Cations; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D045703:Emulsifying Agents; D004655:Emulsions; D005079:Excipients; D005782:Gels; D009883:Ophthalmic Solutions; D013501:Surface-Active Agents; D000069559:Loteprednol Etabonate
Loteprednol etabonate; ex vivo transcorneal permeation; in-situ gel; ocular cationic nanoemulsion; pharmacokinetic study