Nimodipine Ophthalmic Formulations for Management of Glaucoma

• Published in: Pharmaceutical research Vol. 34; no. 4; pp. 809 - 824
• Main Authors: Maria, Doaa Nabih, Abd-Elgawad, Abd-Elgawad Helmy, Soliman, Osama Abd-Elazeem, El-dahan, Marwa Salah, Jablonski, Monica M.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-04-2017; Springer; Springer Nature B.V
• Subjects: 2-Hydroxypropyl-beta-cyclodextrin - chemistry; Administration, Ophthalmic; Animals; beta-Cyclodextrins - chemistry; Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Brinzolamide; Chemistry, Pharmaceutical; Chitosan - chemistry; Clinical outcomes; Cyclodextrins; Cytotoxicity; Drug Liberation; Freeze Drying; Glaucoma; Glaucoma - drug therapy; Hypromellose Derivatives - chemistry; Intraocular Pressure; Medical Law; Mice; Mice, Inbred C57BL; Nimodipine; Nimodipine - chemistry; Nimodipine - pharmacology; Ophthalmic Solutions; Pharmacology/Toxicology; Pharmacy; Prescription drugs; Research Paper; IOP; nimodipine; ophthalmic; cytotoxicity; cyclodextrin
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-017-2110-x

Purpose
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.
Methods
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.
Results
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
.
Conclusions
Nimodipine can be used as a promising topical drug for management of glaucoma through ocular delivery.