Preservative free pharmaceutical ophthalmic compositions

Inventors

Karavas, Evangelos • KOUTRIS, EFTHYMIOS • SAMARA, VASILIKI • Koutri, Ioanna • Kalaskani, Anastasia • KAKOURIS, ANDREAS • FOUSTERIS, MANOLIS

Assignees

Pharmathen SA

Abstract

The present invention relates to a preservative-free ophthalmic composition for the reduction of elevated intraocular pressure containing Latanoprost or a combination of Latanoprost and Timolol and to a process for preparing such compositions.

Core Innovation

The invention provides a preservative-free aqueous ophthalmic pharmaceutical composition for reducing elevated intraocular pressure. The composition contains Latanoprost, optionally in combination with Timolol, and is formulated with at least one Latanoprost solubilizing agent having an hydrophilic-lipophilic balance (HLB) value >10 selected from polyoxyl 40 hydrogenated castor oil, polyoxyl 35 castor oil, castor oil poloxamer 407, and mixtures thereof. The solubilizing agent is present in an amount from 1.5% to 5% w/v, together with buffering agents, sodium chloride as a tonicity agent, disodium edetate dehydrate as a chelating agent, water, and optionally a pH adjusting agent.

The formulation addresses prostaglandin insolubility by incorporating HLB>10 solubilizing agents and by controlling pH with sodium phosphate species, including sodium dihydrogen phosphate dihydrate and anhydrous disodium phosphate. The disclosed composition further controls tonicity using sodium chloride and includes disodium edetate dehydrate as a chelating agent. The patent also specifies the Latanoprost amount as 0.005% w/v, and when present Timolol is present in an amount of 0.500% w/v.

The document also describes packaging and sterilization-related aspects intended to support preservative-free use, including sterilization by aseptic filtration using a hydrophilic modified PVDF membrane. It additionally describes a multi-dose container design with an integral bacterial protection system and a dispensing-tip geometry defined by an inner:outer diameter ratio of 1:1 to 1:6. Sterility and robustness testing after storage and in-use sterility challenge are also described, together with extensive physicochemical and stability tables including assay retention and surface tension behavior.

Claims Coverage

The partial content shows three independent claims. Across these claims, the coverage centers on a preservative-free ophthalmic composition combining Latanoprost, optionally with Timolol, with specific HLB>10 solubilizing agents, sodium phosphate buffering, sodium chloride tonicity, disodium edetate dehydrate chelation, water, and optionally pH adjustment, with additional constraints defining quantitative w/v ingredient levels and, in one claim family member, filtration and container-related features.

Across the independent claims, the coverage is directed to preservative-free ophthalmic formulations for elevated intraocular pressure that combine Latanoprost, optionally with Timolol, with HLB>10 Latanoprost solubilizing agents in defined 1.5% to 5% w/v amounts, buffered with sodium phosphate species, made isotonic with sodium chloride, and chelated with disodium edetate dehydrate, with Latanoprost fixed at 0.005% w/v and Timolol fixed at 0.500% w/v when present, and with additional claim coverage specifying particular ingredient sets and concentration ranges at pH 6.00.

Stated Advantages

Documented Applications