Pre-filled pharmaceutical package comprising a liquid formulation of a VEGF-antagonist
Inventors
Brockmeyer, Carsten • Weikart, Christopher • Bennett, Murray Stephen • Giraud, Jean-Pierre • Strungmann, Thomas
Assignees
Klinge Biopharma GmbH • Formycon AG • SiO2 Medical Products LLC
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Publication Number
US-11298405-B2
Publication Date
2022-04-12
Expiration Date
Abstract
A pre-filled pharmaceutical package comprising a liquid formulation of a VEGF-antagonist, for example Ranibizumab, in a pre-filled pharmaceutical package, for example a syringe, cartridge, or vial, made in part or in whole of a thermoplastic polymer, coated on the interior with a tie coating or layer, a barrier coating or layer, a pH protective coating or layer, and optionally a lubricity coating or layer. Stability performance of the VEGF-antagonist packaged in the coated COP vessel comparable to or better than glass was obtained.
Core Innovation
The invention relates to a pre-filled pharmaceutical package containing a liquid formulation of a VEGF-antagonist, wherein the package includes a wall made of cyclic olefin polymer enclosing at least a portion of a lumen. The VEGF-antagonist is identified as Ranibizumab. The package further includes a closure that closes the lumen and contains the liquid formulation in the lumen for intravitreal injection.
The core material concept is a multilayer interior coating system positioned between the cyclic olefin polymer wall and the lumen. A tie coating or layer of SiOxCyHz is disposed on the wall interior surface, followed by a barrier coating or layer of SiOx, and then a pH protective coating or layer of SiOxCyHz. Layer placement is defined such that the tie layer is between the wall and the barrier layer, while the pH protective layer is positioned between the barrier layer and the lumen.
Additional compatibility is addressed by a lubricity coating or layer positioned between the pH protective coating or layer and the lumen, having atomic proportions SiOxCyHz. The layer compositions are constrained by ranges of x, y, and z as measured by XPS, and by z as measured by at least one of Rutherford backscattering spectrometry or hydrogen forward scattering. The stated results describe stability of VEGF-antagonists in the coated COP vessels as comparable to or better than glass, including decomposition products and aggregates/higher molecular weight species, with evaluation using multiple analytical measures.
Claims Coverage
Independent claim 1 defines the overall pre-filled pharmaceutical package with multiple interior SiOxCyHz/SiOx layers and a lubricity layer, including specified layer composition constraints measured by XPS and at least one of RBS or HFS. The independent claim coverage present in the provided excerpt is limited to claim 1.
Multilayer SiOxCyHz/SiOx interior coating on cyclic olefin polymer wall
A pre-filled pharmaceutical package comprising a liquid formulation of a VEGF-antagonist, wherein the package wall comprises a cyclic olefin polymer with an interior surface, and includes a tie coating or layer on the wall interior surface comprising SiOxCyHz; a barrier coating or layer of SiOx positioned between the tie coating or layer and the lumen; and a pH protective coating or layer of SiOxCyHz positioned between the barrier coating or layer and the lumen.
Specified layer composition constraints measured by XPS and RBS/HFS
The tie coating or layer has x, y, and z ranges as measured by XPS and z measured by at least one of Rutherford backscattering spectrometry or hydrogen forward scattering; the barrier coating or layer has an x range as measured by XPS; and the pH protective coating or layer has x, y, and z ranges as measured by XPS and z measured by at least one of RBS or HFS.
Lubricity coating or layer positioned between pH protective layer and lumen
A lubricity coating or layer positioned between the pH protective coating or layer and the lumen, wherein the lubricity coating or layer has atomic proportions SiOxCyHz with x, y, and z ranges as measured by XPS and at least one of RBS or HFS.
Ranibizumab in the lumen of a closed pre-filled package
A liquid formulation of a VEGF-antagonist in the lumen, a closure closing the lumen, wherein the VEGF antagonist is Ranibizumab.
The provided independent claim coverage centers on a cyclic olefin polymer pre-filled pharmaceutical package with a specified multilayer interior coating stack, plus an additional lubricity coating layer also defined by SiOxCyHz proportions, with measurement constraints defined by XPS and at least one of RBS or HFS, and containing Ranibizumab in the lumen.
Stated Advantages
Stability of VEGF antagonists in coated COP vessels can be comparable to or better than glass.
The document describes evaluation of decomposition products and aggregates/higher molecular weight species, and associated stability measures, for coated COP versus glass.
Documented Applications
Use as a pre-filled pharmaceutical package for a VEGF-antagonist liquid formulation in a lumen, for intravitreal injection.
Administering Ranibizumab as a VEGF antagonist for treatment of an ocular disease in a patient.
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