Ocular ketoconazole-loaded proniosomal gels: formulation, ex vivo corneal permeation and in vivo studies.
BACKGROUND
Vesicular drug carriers for ocular delivery have gained a real potential. Proniosomal gels as ocular drug carriers have been proven to be an effective way to improve bioavailability and patient compliance.


OBJECTIVE
Formulation and in vitro/ex vivo/in vivo characterization of ketoconazole (KET)-loaded proniosomal gels for the treatment of ocular keratitis.


METHODS
The effect of formulation variables; HLB value, type and concentration of non-ionic surfactants (Tweens, Spans, Brijs and Pluronics) with or without lecithin on the entrapment efficiency (EE%), vesicle size and in vitro KET release was evaluated. An ex vivo corneal permeation study to determine the level of KET in the external eye tissue of albino rabbits and an in vivo assessment of the level of KET in the aqueous humors were performed.


CONCLUSIONS
In vivo evaluation showed an increase in bioavailability up to 20-folds from the optimum KET proniosomal gel formula in the aqueous humor compared to drug suspension (KET-SP). The selected formulae were composed of spans being hydrophobic suggesting the potential use of a more hydrophobic surfactant as Span during the formulation of formulae. Factors that stabilize the vesicle membrane and increase the entrapment efficiency of KET (namely low HLB, long alkyl chain, high phase transition temperature) slowed down the release profile.


CONCLUSIONS
Proniosomal gels as drug delivery carriers were proven to be a promising approach to increase corneal contact and permeation as well as retention time in the eye resulting in a sustained action and enhanced bioavailability.
a Department Pharmaceutics and Industrial Pharmacy , Faculty of Pharmacy, Cairo University , Cairo , Egypt and.
Ghada A
GA
Abdelbary
a Department Pharmaceutics and Industrial Pharmacy , Faculty of Pharmacy, Cairo University , Cairo , Egypt and.
Maha M
MM
Amin
b Department Pharmaceutics and Industrial Pharmacy , Faculty of Pharmacy, Sinai University , Sinai , Egypt.
Mohamed Y
MY
Zakaria
D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000378:metabolism*; D003315:Cornea / Q000187:drug effects / Q000378:metabolism*; D004337:Drug Carriers / Q000008:administration & dosage / Q000378:metabolism*; D065546:Drug Liberation; D005782:Gels; D007654:Ketoconazole / Q000008:administration & dosage / Q000378:metabolism*; D008081:Liposomes / Q000008:administration & dosage / Q000378:metabolism*; D008297:Male; D009924:Organ Culture Techniques; D010539:Permeability / Q000187:drug effects; D011355:Prodrugs / Q000008:administration & dosage / Q000378:metabolism*; D011817:Rabbits
D000935:Antifungal Agents; D004337:Drug Carriers; D005782:Gels; D008081:Liposomes; D011355:Prodrugs; D007654:Ketoconazole
Proniosomal gel; ex vivo corneal permeation; ketoconazole; ocular delivery; ocular keratitis