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-10925927-B2
Publication Date
2021-02-23
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 disclosure describes a pre-filled pharmaceutical package comprising a liquid formulation of a VEGF-antagonist in a lumen closed by a closure. The package includes a wall comprising a thermoplastic material and an interior surface enclosing at least a portion of the lumen.
The interior wall surface is provided with a sequential set of a SiOxCyHz tie coating or layer, a SiOx barrier coating or layer, and a SiOxCyHz pH protective coating or layer positioned between the coatings and the lumen. The tie coating or layer and the pH protective coating or layer are defined by atomic proportions measured by X-ray photoelectron spectroscopy and by Rutherford backscattering spectrometry or hydrogen forward scattering.
The liquid formulation of a VEGF-antagonist in the lumen has less aggregates after storage for 3 months at 25 or 40°C than the same liquid formulation stored under the same conditions in a lumen of a pre-filled pharmaceutical package having a wall made of borosilicate glass and lacking the tie coating, the barrier coating, and the pH protective coating. The package is exemplified with cyclic olefin polymer, and optional fluoropolymer lubricity on a closure face can be included.
Claims Coverage
The document provides one independent claim with four inventive features defining the thermoplastic package structure, the sequential SiOxCyHz/SiOx coatings with composition ranges, and a stability criterion after storage. Dependent claims further specify VEGF-antagonist selection and additional quantitative constraints on package performance.
Pre-filled package with VEGF-antagonist liquid formulation and closure
A pre-filled pharmaceutical package comprising a liquid formulation of a VEGF-antagonist, wherein the package comprises a wall comprising a thermoplastic material having an interior surface enclosing at least a portion of a lumen, and a closure closing the lumen.
Sequential tie, barrier, and pH protective coating architecture
A tie coating or layer comprising SiOxCyHz on the interior surface, a barrier coating or layer comprising SiOx positioned between the tie coating or layer and the lumen, and a pH protective coating or layer comprising SiOxCyHz positioned between the barrier coating or layer and the lumen.
Coating composition ranges defined by XPS and RBS or HFS
The tie coating or layer and the pH protective coating or layer comprise SiOxCyHz with atomic proportions defined by X-ray photoelectron spectroscopy and by at least one of Rutherford backscattering spectrometry or hydrogen forward scattering, and the barrier coating or layer comprises SiOx defined by X-ray photoelectron spectroscopy.
Reduced aggregation after storage compared to borosilicate glass
The liquid formulation of a VEGF-antagonist in the lumen has less aggregates after storage for 3 months at 25 or 40°C than the same liquid formulation stored under the same conditions in a lumen of a pre-filled pharmaceutical package having a wall made of borosilicate glass and lacking the tie coating, the barrier coating, and the pH protective coating.
Overall, the claim coverage focuses on a pre-filled thermoplastic pharmaceutical container whose interior surface is defined by sequential SiOxCyHz tie, SiOx barrier, and SiOxCyHz pH protective layers, combined with reduced aggregates of a VEGF-antagonist liquid formulation after storage versus a borosilicate glass comparison lacking those layers.
Stated Advantages
Less aggregates after storage for 3 months at 25 or 40°C compared to a borosilicate-glass lumen lacking the tie, barrier, and pH protective layers.
Documented Applications
A pre-filled ophthalmic pharmaceutical package containing a liquid VEGF-antagonist formulation, where the package interior includes specified sequential SiOxCyHz/SiOx coatings to support stability relative to borosilicate glass controls.
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