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Preparation of ophthalmic formulations containing cilostazol as an anti-glaucoma agent and improvement in its permeability through the rabbit cornea.
J Oleo Sci 2010; 59(8):423-30JO

Abstract

To evaluate the pharmacological properties of cilostazol (CLZ), we examined its intraocular pressure (IOP) -lowering effect. CLZ is an inhibitor of Type III phosphodiesterase that increases intracellular cyclic AMP levels by restraining platelet aggregation, and has a potential protective effect against atherosclerosis. We attempted to apply it for use as an anti-glaucoma agent; however, the application of CLZ in the ophthalmic field is limited due to its poor water solubility. We attempted to enhance CLZ solubility using 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD). The solubility of CLZ increased with increasing HPbetaCD concentrations, and 0.05% CLZ was dissolved in 10% HPbetaCD. Moreover, fine particle suspension of 0.5% CLZ in 5% HPbetaCD (soluble CLZ: ca. 0.027%) were prepared using a Microfluidizer, an impact-type emulsifying comminution device. In an in vitro transcorneal penetration experiment through the rabbit cornea, the CLZ penetration rate was dependent on the CLZ content of the solutions and suspensions. When a 0.05% CLZ ophthalmic solution was instilled into a rabbit eye, the absorption rate constant for CLZ into an aqueous humor was 0.0059+/-0.001 min(-1), and the elimination rate constant was 0.048+/-0.024 min(-1). Also CLZ ophthalmic solutions and fine particle suspension were examined to for their ability to reduce enhanced intraocular pressure (IOP) of rabbits in a darkroom. The instillation of 0.05% CLZ ophthalmic solutions and 0.5% CLZ fine particle suspensions into rabbit eyes reduced the enhanced IOP. These results demonstrate that the instillation of CLZ ophthalmic solutions and fine particle suspensions may represent an effective anti-glaucoma formulation.

Authors+Show Affiliations

Department of Ophthalmology, Hyogo Medical College, Nishinomiya, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

20625234

Citation

Okamoto, Norio, et al. "Preparation of Ophthalmic Formulations Containing Cilostazol as an Anti-glaucoma Agent and Improvement in Its Permeability Through the Rabbit Cornea." Journal of Oleo Science, vol. 59, no. 8, 2010, pp. 423-30.
Okamoto N, Ito Y, Nagai N, et al. Preparation of ophthalmic formulations containing cilostazol as an anti-glaucoma agent and improvement in its permeability through the rabbit cornea. J Oleo Sci. 2010;59(8):423-30.
Okamoto, N., Ito, Y., Nagai, N., Murao, T., Takiguchi, Y., Kurimoto, T., & Mimura, O. (2010). Preparation of ophthalmic formulations containing cilostazol as an anti-glaucoma agent and improvement in its permeability through the rabbit cornea. Journal of Oleo Science, 59(8), pp. 423-30.
Okamoto N, et al. Preparation of Ophthalmic Formulations Containing Cilostazol as an Anti-glaucoma Agent and Improvement in Its Permeability Through the Rabbit Cornea. J Oleo Sci. 2010;59(8):423-30. PubMed PMID: 20625234.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Preparation of ophthalmic formulations containing cilostazol as an anti-glaucoma agent and improvement in its permeability through the rabbit cornea. AU - Okamoto,Norio, AU - Ito,Yoshimasa, AU - Nagai,Noriaki, AU - Murao,Takatoshi, AU - Takiguchi,Yusuke, AU - Kurimoto,Takuji, AU - Mimura,Osamu, PY - 2010/7/14/entrez PY - 2010/7/14/pubmed PY - 2010/10/30/medline SP - 423 EP - 30 JF - Journal of oleo science JO - J Oleo Sci VL - 59 IS - 8 N2 - To evaluate the pharmacological properties of cilostazol (CLZ), we examined its intraocular pressure (IOP) -lowering effect. CLZ is an inhibitor of Type III phosphodiesterase that increases intracellular cyclic AMP levels by restraining platelet aggregation, and has a potential protective effect against atherosclerosis. We attempted to apply it for use as an anti-glaucoma agent; however, the application of CLZ in the ophthalmic field is limited due to its poor water solubility. We attempted to enhance CLZ solubility using 2-hydroxypropyl-beta-cyclodextrin (HPbetaCD). The solubility of CLZ increased with increasing HPbetaCD concentrations, and 0.05% CLZ was dissolved in 10% HPbetaCD. Moreover, fine particle suspension of 0.5% CLZ in 5% HPbetaCD (soluble CLZ: ca. 0.027%) were prepared using a Microfluidizer, an impact-type emulsifying comminution device. In an in vitro transcorneal penetration experiment through the rabbit cornea, the CLZ penetration rate was dependent on the CLZ content of the solutions and suspensions. When a 0.05% CLZ ophthalmic solution was instilled into a rabbit eye, the absorption rate constant for CLZ into an aqueous humor was 0.0059+/-0.001 min(-1), and the elimination rate constant was 0.048+/-0.024 min(-1). Also CLZ ophthalmic solutions and fine particle suspension were examined to for their ability to reduce enhanced intraocular pressure (IOP) of rabbits in a darkroom. The instillation of 0.05% CLZ ophthalmic solutions and 0.5% CLZ fine particle suspensions into rabbit eyes reduced the enhanced IOP. These results demonstrate that the instillation of CLZ ophthalmic solutions and fine particle suspensions may represent an effective anti-glaucoma formulation. SN - 1347-3352 UR - https://www.unboundmedicine.com/medline/citation/20625234/Preparation_of_ophthalmic_formulations_containing_cilostazol_as_an_anti_glaucoma_agent_and_improvement_in_its_permeability_through_the_rabbit_cornea_ L2 - http://joi.jlc.jst.go.jp/JST.JSTAGE/jos/59.423?lang=en&from=PubMed DB - PRIME DP - Unbound Medicine ER -