title: Preparation and in vitro/in vivo evaluation of antimicrobial ocular in situ gels containing a disappearing preservative for topical treatment of bacterial conjunctivitis.
abstract: The study aimed to formulate and evaluate levofloxacin hemihydrate ocular in situ gels along with freshly prepared disappearing preservative reported to be safer to human eyes. Formulae were prepared using thermosensitive (PF127 and PF68) or ion-activated (Gelrite) polymers. They were evaluated for gelation temperature (GT), capacity, content uniformity, pH, rheological behavior, in vitro drug release with kinetic analysis. Best formulae were exposed to storage effect to select the optimum formula that was subjected to different sterilization methods and in vivo evaluation. The prepared disappearing preservative (sodium perborate monohydrate) proved to be active oxidative preservative and compatible with our formulae. F9 (24% PF127, 15% PF 68, 0.5% levofloxacin hemihydrate, and 0.0025% sodium perborate monohydrate) showed prolonged drug release (12 h), acceptable GT, viscosity, and pH. It remained stable over 3 months at two temperatures and was best sterilized by filtration. It showed longer residence time (12 h) in rabbits' eye fluids compared with the Levoxin® eye drops (4 h). This successful attempt of using thermo-gelling system along with a disappearing type of preservatives would allow the use of these systems to achieve sustained release of antimicrobial drugs with minimum risk of eye damage improving patient compliance and treatment efficacy.
authors.affiliation: a Department Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy , Cairo University , Cairo , Egypt.
authors.forename: Osama
authors.initials: O
authors.lastname: Saher
authors.affiliation: a Department Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy , Cairo University , Cairo , Egypt.
authors.forename: Dalia M
authors.initials: DM
authors.lastname: Ghorab
authors.affiliation: a Department Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy , Cairo University , Cairo , Egypt.
authors.forename: Nadia M
authors.initials: NM
authors.lastname: Mursi
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D003234:Conjunctivitis, Bacterial / Q000188:drug therapy* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005782:Gels; D009883:Ophthalmic Solutions; D011310:Preservatives, Pharmaceutical / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics; D011817:Rabbits; D013211:Staphylococcus aureus / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: D000890:Anti-Infective Agents; D005782:Gels; D009883:Ophthalmic Solutions; D011310:Preservatives, Pharmaceutical
keywords: Bacterial conjunctivitis; disappearing preservative; in situ gels; levofloxacin; ocular drug delivery