Nimodipine Ophthalmic Formulations for Management of Glaucoma.
Preparation and evaluation of topical ophthalmic formulations containing nimodipine-CD complexes prepared using HP-β-CD, SBE-β-CD and M-β-CD for the management of glaucoma.



Nimodipine-CD complexes were prepared using a freeze-drying method. Two different molar ratios (NMD:CD) were used for each cyclodextrin. The inclusion complexes were characterized using DSC, FTIR, yield (%), drug content and in vitro release characteristics. NMD-CD complexes incorporated into chitosan eye drops and a temperature-triggered in situ gelling system were evaluated for their pH, viscosity and in vitro release characteristics. We determined the intraocular pressure (IOP) lowering effect of NMD-hydroxypropylmethylcellulose (HPMC) eye drops through a single dose response design using C57BL/6J mice. The minimum effective concentration (MEC) of nimodipine was further applied to mice that vary in the parental allele of Cacna1s, the drug target of nimodipine. Cytotoxicity was also evaluated.



Our ophthalmic formulations possessed pH and viscosity values that are compatible with the eye. In vitro release of nimodipine was significantly increased from chitosan eye drops containing NMD-CD complexes compared to uncomplexed drug. Administration of nimodipine can lower IOP significantly after a single drop of drug HPMC suspension. The IOP-lowering response of the MEC (0.6%) was significantly influenced by the parental allele of Cacna1s.



Nimodipine can be used as a promising topical drug for management of glaucoma through ocular delivery.
Department of Ophthalmology, Hamilton Eye Institute, The University of Tennessee Health Science Center, 930 Madison Avenue, Suite 731, Memphis, Tennessee, 38163, USA.|Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee, USA.|Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
Doaa Nabih
DN
Maria
Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
Abd-Elgawad Helmy
AH
Abd-Elgawad
Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
Osama Abd-Elazeem
OA
Soliman
Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt.
Marwa Salah
MS
El-Dahan
Department of Ophthalmology, Hamilton Eye Institute, The University of Tennessee Health Science Center, 930 Madison Avenue, Suite 731, Memphis, Tennessee, 38163, USA. mjablonski@uthsc.edu.|Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee, USA. mjablonski@uthsc.edu.
Monica M
MM
Jablonski
D000073738:2-Hydroxypropyl-beta-cyclodextrin / Q000737:chemistry; D060433:Administration, Ophthalmic; D000818:Animals; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry; D065546:Drug Liberation; D005612:Freeze Drying; D005901:Glaucoma / Q000188:drug therapy*; D065347:Hypromellose Derivatives / Q000737:chemistry; D007429:Intraocular Pressure; D008810:Mice, Inbred C57BL; D009553:Nimodipine / Q000737:chemistry / Q000494:pharmacology*; D009883:Ophthalmic Solutions; D047392:beta-Cyclodextrins / Q000737:chemistry
D009883:Ophthalmic Solutions; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; C093196:SBE4-beta-cyclodextrin; D065347:Hypromellose Derivatives; D009553:Nimodipine; D048271:Chitosan
IOP; cyclodextrin; cytotoxicity; nimodipine; ophthalmic