Physiochemical Properties and Cytotoxicity of a Benzalkonium Chloride-Free, Micellar Emulsion Ophthalmic Formulation of Latanoprost

Arindam Halder, Ajay J Khopade Formulation Department, Sun Pharmaceutical Industries, Ltd, Tandalja, Vadodara, IndiaCorrespondence: Ajay J KhopadeSun Pharmaceutical Industries, Ltd., Tandalja, Vadodara 390020, Gujarat, IndiaTel +91 22 6645 5645 Ext 1900Email ajay.khopade@sunpharma.comPurpose: Prosta...

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Autores principales:	Halder A, Khopade AJ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	open angle glaucoma micelle formulation benzalkonium chloride latanoprost Ophthalmology RE1-994
Acceso en línea:	https://doaj.org/article/af7294b0dee04c9cb30ddfa2ca1659bc
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spelling	oai:doaj.org-article:af7294b0dee04c9cb30ddfa2ca1659bc2021-12-02T12:15:56ZPhysiochemical Properties and Cytotoxicity of a Benzalkonium Chloride-Free, Micellar Emulsion Ophthalmic Formulation of Latanoprost1177-5483https://doaj.org/article/af7294b0dee04c9cb30ddfa2ca1659bc2020-10-01T00:00:00Zhttps://www.dovepress.com/physiochemical-properties-and-cytotoxicity-of-a-benzalkonium-chloride--peer-reviewed-article-OPTHhttps://doaj.org/toc/1177-5483Arindam Halder, Ajay J Khopade Formulation Department, Sun Pharmaceutical Industries, Ltd, Tandalja, Vadodara, IndiaCorrespondence: Ajay J KhopadeSun Pharmaceutical Industries, Ltd., Tandalja, Vadodara 390020, Gujarat, IndiaTel +91 22 6645 5645 Ext 1900Email ajay.khopade@sunpharma.comPurpose: Prostaglandin derivatives are used widely to reduce intraocular pressure associated with open-angle glaucoma. The most widely used prostaglandin derivative, latanoprost, is available in an ophthalmic solution that is solubilized and preserved with 0.02% benzalkonium chloride (BAK), which has been shown to be cytotoxic to corneal cells. Latanoprost ophthalmic solution with BAK requires specific storage temperatures, which can impact the supply cycle. Here, we describe the production, physicochemical characteristics, and cytotoxicity profile of a micelle formulation that solubilizes latanoprost without the need for BAK.Methods: The optimum concentration of castor oil with the surfactant polyethylene glycol (15) hydroxystearate was determined, and the mixture stirred. Various surfactants were tested to determine the ideal mixture to form a micelle formulation. Viscosity, zeta potential, surface tension, droplet size, and osmolality of the batches were tested. The cytotoxicity of the micelle formulation was determined in a corneal cell viability assay that compared positive and negative controls, latanoprost without BAK, latanoprost with BAK, and placebo.Results: A castor oil concentration of 0.15% produced a micelle formulation with a diameter of < 100 nm. This micelle formulation had unique characteristics that were not mimicked when either the surfactant or the oil was changed. The physicochemical characteristics in multiple batches of the micelle formulation did not vary significantly between batches. Long-term and accelerated stability studies showed latanoprost potency remained constant for 24 months at 25°C/75% relative humidity (RH) and at 40°C/25% RH for 6 months.Conclusion: The micelle formulation technology system is capable of solubilizing latanoprost in an ophthalmic formulation without the need for BAK. The system is stable at room temperature.Keywords: open angle glaucoma, micelle formulation, benzalkonium chloride, latanoprostHalder AKhopade AJDove Medical Pressarticleopen angle glaucomamicelle formulationbenzalkonium chloridelatanoprostOphthalmologyRE1-994ENClinical Ophthalmology, Vol Volume 14, Pp 3057-3064 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	open angle glaucoma micelle formulation benzalkonium chloride latanoprost Ophthalmology RE1-994
spellingShingle	open angle glaucoma micelle formulation benzalkonium chloride latanoprost Ophthalmology RE1-994 Halder A Khopade AJ Physiochemical Properties and Cytotoxicity of a Benzalkonium Chloride-Free, Micellar Emulsion Ophthalmic Formulation of Latanoprost
description	Arindam Halder, Ajay J Khopade Formulation Department, Sun Pharmaceutical Industries, Ltd, Tandalja, Vadodara, IndiaCorrespondence: Ajay J KhopadeSun Pharmaceutical Industries, Ltd., Tandalja, Vadodara 390020, Gujarat, IndiaTel +91 22 6645 5645 Ext 1900Email ajay.khopade@sunpharma.comPurpose: Prostaglandin derivatives are used widely to reduce intraocular pressure associated with open-angle glaucoma. The most widely used prostaglandin derivative, latanoprost, is available in an ophthalmic solution that is solubilized and preserved with 0.02% benzalkonium chloride (BAK), which has been shown to be cytotoxic to corneal cells. Latanoprost ophthalmic solution with BAK requires specific storage temperatures, which can impact the supply cycle. Here, we describe the production, physicochemical characteristics, and cytotoxicity profile of a micelle formulation that solubilizes latanoprost without the need for BAK.Methods: The optimum concentration of castor oil with the surfactant polyethylene glycol (15) hydroxystearate was determined, and the mixture stirred. Various surfactants were tested to determine the ideal mixture to form a micelle formulation. Viscosity, zeta potential, surface tension, droplet size, and osmolality of the batches were tested. The cytotoxicity of the micelle formulation was determined in a corneal cell viability assay that compared positive and negative controls, latanoprost without BAK, latanoprost with BAK, and placebo.Results: A castor oil concentration of 0.15% produced a micelle formulation with a diameter of < 100 nm. This micelle formulation had unique characteristics that were not mimicked when either the surfactant or the oil was changed. The physicochemical characteristics in multiple batches of the micelle formulation did not vary significantly between batches. Long-term and accelerated stability studies showed latanoprost potency remained constant for 24 months at 25°C/75% relative humidity (RH) and at 40°C/25% RH for 6 months.Conclusion: The micelle formulation technology system is capable of solubilizing latanoprost in an ophthalmic formulation without the need for BAK. The system is stable at room temperature.Keywords: open angle glaucoma, micelle formulation, benzalkonium chloride, latanoprost
format	article
author	Halder A Khopade AJ
author_facet	Halder A Khopade AJ
author_sort	Halder A
title	Physiochemical Properties and Cytotoxicity of a Benzalkonium Chloride-Free, Micellar Emulsion Ophthalmic Formulation of Latanoprost
title_short	Physiochemical Properties and Cytotoxicity of a Benzalkonium Chloride-Free, Micellar Emulsion Ophthalmic Formulation of Latanoprost
title_full	Physiochemical Properties and Cytotoxicity of a Benzalkonium Chloride-Free, Micellar Emulsion Ophthalmic Formulation of Latanoprost
title_fullStr	Physiochemical Properties and Cytotoxicity of a Benzalkonium Chloride-Free, Micellar Emulsion Ophthalmic Formulation of Latanoprost
title_full_unstemmed	Physiochemical Properties and Cytotoxicity of a Benzalkonium Chloride-Free, Micellar Emulsion Ophthalmic Formulation of Latanoprost
title_sort	physiochemical properties and cytotoxicity of a benzalkonium chloride-free, micellar emulsion ophthalmic formulation of latanoprost
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/af7294b0dee04c9cb30ddfa2ca1659bc
work_keys_str_mv	AT haldera physiochemicalpropertiesandcytotoxicityofabenzalkoniumchloridefreemicellaremulsionophthalmicformulationoflatanoprost AT khopadeaj physiochemicalpropertiesandcytotoxicityofabenzalkoniumchloridefreemicellaremulsionophthalmicformulationoflatanoprost
_version_	1718394594251505664

Physiochemical Properties and Cytotoxicity of a Benzalkonium Chloride-Free, Micellar Emulsion Ophthalmic Formulation of Latanoprost

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