Hollow body having a wall with a layer of glass and a plurality of particles

Abstract

A hollow body includes a wall which at least partially surrounds an interior volume of the hollow body. The wall includes a layer of glass and has a wall surface. The wall surface includes a surface region in which the layer of glass is at least partially superimposed by a plurality of particles. The plurality of particles is characterized by a particle size distribution having a D.sub.50 in a range from 1 to 100 μm. A hollow body having a wall surface including a surface region which is characterized by a coefficient of dry sliding friction of less than 0.15 is also provided.

Claims

1. A hollow body, comprising: a wall which at least partially surrounds an interior volume of the hollow body, the wall comprising a layer of glass and having a wall surface with a surface region; and a plurality of particles at least partially superimposing the layer of glass in the surface region of the wall surface, the plurality of particles being characterized by a particle size distribution having a D.sub.50 in a range from 1 μm to 100 μm, wherein the plurality of particles is not embedded in any material and the surface region is characterized by a coefficient of dry sliding friction of less than 0.15.

2. The hollow body of claim 1, wherein the particles of the plurality of particles are selected from the group consisting of organic particles, inorganic particles, hybrid polymer particles, or a combination of at least two thereof.

3. The hollow body of claim 2, wherein the particles comprise inorganic particles and the inorganic particles are selected from the group consisting of a boron nitride, a molybdenum sulfide, a silicon nitride, an oxide, a compound which includes covalently bonded H, or a combination of at least two thereof.

4. The hollow body of claim 1, wherein the particles of the plurality of particles comprise a compound which includes covalently bonded H.

5. The hollow body of claim 1, wherein the particles of the plurality of particles adjoin the layer of glass in the surface region of the wall surface.

6. The hollow body of claim 1, wherein the particles of the plurality of particles are not superimposed by any component of the wall surface on a side of the particles of the plurality of particles which faces away from the layer of glass.

7. The hollow body of claim 1, wherein the particles of the plurality of particles are characterized by an aspect ratio in a range from 0.5 to 1.5.

8. A hollow body, comprising: a wall which at least partially surrounds an interior volume of the hollow body, the wall comprising a layer of glass and having a wall surface, the wall surface comprising a surface region which is characterized by a coefficient of dry sliding friction of less than 0.15; and a plurality of particles at least partially superimposing the layer of glass in the surface region of the wall surface that is characterized by a particle size distribution having a D.sub.50 in a range from 1 μm to 100 μm.

9. The hollow body of claim 8, wherein the surface region is further characterized by a contact angle for wetting with water in a range from 0° to 45°.

10. The hollow body of claim 8, wherein the hollow body is a container.

11. The hollow body of claim 10, wherein the container is a packaging container for at least one of a medical packaging good or a pharmaceutical packaging good.

12. A process for making an item, the process comprising as process steps: a) providing a hollow body comprising a wall which at least partially surrounds an interior volume of the hollow body, the wall comprising a layer of glass and having a wall surface; b) superimposing at least a part of the layer of glass with a composition comprising a first plurality of particles and a vehicle; and c) decreasing a proportion of the vehicle in the composition, thereby leaving at least a part of the first plurality of particles or a further plurality of particles, which is obtained in the process step c) from at least a part of the first plurality of particles, or a combination of the first plurality of particles and the further plurality of particles superimposed on the layer of glass in a surface region of the wall surface, the superimposed plurality of particles on the surface region being characterized by a particle size distribution having a D.sub.50 in a range from 1 to 100 μm, wherein the surface region is characterized by a coefficient of dry sliding friction of less than 0.15.

13. The process of claim 12, wherein in the process step b) the composition comprises the first plurality of particles at a proportion in a range from 0.1 wt.-% to 25 wt.-%, based on the weight of the composition in the process step b).

14. The process of claim 12, wherein in the process step b) the layer of glass is contacted with the composition.

15. A closed container, comprising: a wall at least partially surrounding an interior volume which comprises a pharmaceutical composition, the wall comprising a layer of glass and having a wall surface comprising a surface region, the closed container meeting both of the following criteria: A. the layer of glass is at least partially superimposed by a plurality of particles in the surface region, the plurality of particles being characterized by a particle size distribution having a D.sub.50 in a range from 1 to 100 μm; and B. the surface region is characterized by a coefficient of dry sliding friction of less than 0.15.

16. A process, comprising as process steps: providing a hollow body comprising a wall which at least partially surrounds an interior volume of the hollow body, the wall comprising a layer of glass and having a wall surface with a surface region, and a plurality of particles at least partially superimposing the layer of glass in the surface region of the wall, the plurality of particles being characterized by a particle size distribution having a D.sub.50 in a range from 1 μm to 100 μm, wherein the surface region is characterized by a coefficient of dry sliding friction of less than 0.15; inserting a pharmaceutical composition into the interior volume; and closing the hollow body.

17. A process, comprising: using a plurality of particles to adjust a coefficient of dry sliding friction of a surface of glass of a container to be less than 0.15, the plurality of particles being characterized by a particle size distribution having a D.sub.50 in a range from 1 μm to 100 μm.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) The above-mentioned and other features and advantages of this invention, and the manner of attaining them, will become more apparent and the invention will be better understood by reference to the following description of embodiments of the invention taken in conjunction with the accompanying drawings, wherein:

(2) FIG. 1 illustrates a schematic depiction of an exemplary embodiment of a hollow body provided according to the invention;

(3) FIG. 2 illustrates a schematic depiction of another exemplary embodiment of a hollow body provided according to the invention;

(4) FIG. 3 illustrates a schematic depiction of exemplary embodiments of a closed hollow body and a closed container provided according to the invention;

(5) FIG. 4 illustrates a flow chart of an exemplary embodiment of a process provided according to the invention for the preparation of a hollow body;

(6) FIG. 5 illustrates a flow chart of another exemplary embodiment of a process provided according to the invention for the preparation of a hollow body;

(7) FIG. 6 illustrates a flow chart of an exemplary embodiment of a process provided according to the invention for packaging a pharmaceutical composition;

(8) FIG. 7 illustrates a flow chart of an exemplary embodiment of a process provided according to the invention for treating a patient;

(9) FIG. 8 illustrates a schematic depiction of the positions on the interior surface of vials at which the contact angle for wetting with water has been measured in the studies of contamination of the interior surface due to a washing process;

(10) FIG. 9 illustrates results of the studies of contamination of the interior surface due to a washing process for exemplary vials;

(11) FIG. 10 illustrates a diagram with results of measurements of the coefficient of dry sliding friction of exemplary vials and comparative examples;

(12) FIG. 11 illustrates results of measurements of the transmission coefficient of exemplary vials and the comparative example;

(13) FIG. 12 illustrates a microscope image of the exterior surface of an exemplary vial;

(14) FIG. 13 illustrates a further microscope image of the exterior surface of an exemplary vial;

(15) FIG. 14 illustrates a microscope image of the exterior surface of an exemplary vial prior to freeze drying; and

(16) FIG. 15 illustrates a microscope image of the exterior surface of an exemplary vial after freeze drying.

(17) Corresponding reference characters indicate corresponding parts throughout the several views. The exemplifications set out herein illustrate embodiments of the invention and such exemplifications are not to be construed as limiting the scope of the invention in any manner.

DETAILED DESCRIPTION OF THE INVENTION

(18) Hollow Body

(19) The hollow body according to the invention may have any size or shape which the skilled person deems appropriate in the context of the invention. In some embodiments, the head region of the hollow body comprises an opening, which allows for inserting a pharmaceutical composition into the interior volume of the hollow body. In that case, the wall surrounds the interior volume of the hollow body only partially. The hollow body may be a glass body or a glass container in that sense that the layer of glass extends over the full area of the wall surface. In that case, the layer of glass may determine a macroscopic shape of the wall. In some embodiments, the layer of glass is of a one-piece design. The layer of glass of such a glass body or a glass container may be made by blow molding a glass melt; or by preparing a tube of a glass, such as in form of a hollow cylinder, forming the bottom of the hollow body from one end of the tube, thereby closing the tube at this end, and forming the head region of the hollow body from the opposite end of the tube. According to the nomenclature used herein, the wall of the hollow body comprises the layer of glass and every layer and every functionalization superimposed thereon. The wall surface is formed by the surface of the layer or functionalization, such as particles, which is positioned at an outermost or innermost position of the wall.

(20) As used herein, the interior volume represents the full volume of the interior of the hollow body. This volume may be determined by filling the interior of the hollow body with water up to the brim and measuring the volume of the amount of water which the interior can take up to the brim. Hence, the interior volume as used herein is not a nominal volume as it is often referred to in the technical field of pharmacy. This nominal volume may for example be less than the interior volume by a factor of about 0.5.

(21) Glass

(22) The glass of the layer of glass may be any type of glass and may consist of any material or combination of materials which the skilled person deems suitable in the context of the invention. In some embodiments, the glass is suitable for pharmaceutical packaging and may be of type I in accordance with the definitions of glass types in section 3.2.1 of the European Pharmacopoeia, 7th edition from 2011. Additionally or alternatively to the preceding, the glass may be selected from the group consisting of a borosilicate glass, an aluminosilicate glass, and fused silica; or a combination of at least two thereof. As used herein, an aluminosilicate glass is a glass which has a content of Al.sub.2O.sub.3 of more than 8 wt.-%, such as more than 9 wt.-% or in a range from 9 to 20 wt.-%, in each case based on the total weight of the glass. An exemplary aluminosilicate glass has a content of B.sub.2O.sub.3 of less than 8 wt.-%, such as at maximum 7 wt.-% or in a range from 0 to 7 wt.-%, in each case based on the total weight of the glass. As used herein, a borosilicate glass is a glass which has a content of B.sub.2O.sub.3 of at least 1 wt.-%, such as at least 2 wt.-%, at least 3 wt.-%, at least 4 wt.-%, at least 5 wt.-%, and/or in a range from 5 to 15 wt.-%, in each case based on the total weight of the glass. An exemplary borosilicate glass has a content of Al.sub.2O.sub.3 of less than 7.5 wt.-%, such as less than 6.5 wt.-% and/or in a range from 0 to 5.5 wt.-%, in each case based on the total weight of the glass. In a further aspect, the borosilicate glass has a content of Al.sub.2O.sub.3 in a range from 3 to 7.5 wt.-%, such as in a range from 4 to 6 wt.-%, in each case based on the total weight of the glass.

(23) The glass may be essentially free from B. Herein, the wording “essentially free from B” refers to glasses which are free from B which has been added to the glass composition by purpose. This means that B may still be present as an impurity, but may be at a proportion of not more than 0.1 wt.-%, such as not more than 0.05 wt.-%, in each case based on the weight of the glass.

(24) Particle Size Distribution

(25) The D.sub.50 of a particle size distribution provides the particle diameter for which 50% of all particles of the plurality of particles having this particle size distribution have diameters smaller than this value. The D.sub.10 of a particle size distribution provides the particle diameter for which 10% of all particles of the plurality of particles having this particle size distribution have diameters smaller than this value. The D.sub.90 of a particle size distribution provides the particle diameter for which 90% of all particles of the plurality of particles having this particle size distribution have diameters smaller than this value. Herein, the diameter is the length of the longest straight line which starts and ends on the surface of the particle and which lies fully within the particle. In Cartesian coordinates, the length of a particle lies on one axis, the width of the particle lies on another axis and the thickness on still another axis. Here, the length is more than the width which is more than the thickness of the particle. The aspect ratio is the quotient of length divided by thickness.

(26) Dispersion

(27) The composition of exemplary processes provided according to the invention may be a dispersion. Generally, a dispersion is a system in which particles are dispersed in a continuous phase. There are three main types of dispersions: a coarse dispersion which is also referred to as suspension, a colloid, and a solution. A suspension is a heterogeneous mixture that contains solid particles sufficiently large for sedimentation. The particles may be visible to the naked eye, usually must be larger than 1 micrometre, and will eventually settle. A suspension is a heterogeneous mixture in which the dispersed particles do not dissolve, but get suspended throughout the bulk of the continuous phase, left floating around freely in the medium. The particles may be dispersed throughout the continuous phase through mechanical agitation, with the use of certain excipients or suspending or dispersing agents. The suspended particles are visible under a microscope and will settle over time if left undisturbed. This distinguishes a suspension from a colloid, in which the dispersed particles are smaller and do not settle. Colloids and suspensions are different from a solution, in which the particles do not exist as a solid, but are dissolved. The composition of the invention may be a dispersion in which sold particles, in particular the first plurality of particles, are dispersed in a liquid phase, referred to herein as vehicle. In the context of the composition of the invention, an exemplary dispersion is a suspension.

(28) Vehicle

(29) As the vehicle each vehicle which the skilled person knows and deems appropriate for being used in the context of the invention comes into consideration. Here, the vehicle is a, for example liquid, medium which allows for the at least partially superposition of the first plurality of particles onto the layer of glass in a convenient, uniform, manner. In some embodiments, the vehicle has a viscosity which is suitable for the preceding purpose. The vehicle may have a rather high vapour pressure which allows for decreasing the proportion of the vehicle in the composition through evaporation of the vehicle in the process step c) at a temperature as close to 20° C. as possible. In a case in which the composition is a dispersion, the vehicle may be the continuous, liquid, phase of the dispersion.

(30) Dispersing Agent

(31) In the process step b) of the process provided according to the invention, the composition may comprise one or more dispersing agents. Here, any dispersing agent which the skilled person knows and which he deems appropriate to be utilized in the context of the invention comes into consideration. In some embodiments, the dispersing agent supports keeping the particles of the plurality of particles dispersed throughout the vehicle as homogenously as possible. An exemplary dispersing agent is one selected from the group consisting of a polyacrylic acid, a polyimine, para-toluolsulfonic acid, a polyvinylpyrrolidone, a polyethylenglycol, hydroxypropylcellulose, an additive for inkjet inks, and a wetting or dispersing additive from the DISPERBYK series which is commercially available from BYK-Chemie GmbH, Wesel, Germany; or a combination of at least two thereof. Therein, a polyacrylic acid is a useful dispersing agent if the composition has a pH of more than 7. Further, a polyimine is a useful dispersing agent if the composition has a pH of less than 7. An exemplary additive for inkjet inks is an additive of the BYKJET series which is commercially available from BYK-Chemie GmbH, Wesel, Germany. In a case in which the particles of the first plurality of particles comprise, or consist of, PDMS an alternatively or additionally exemplary dispersing agent is selected from the group consisting of a silicon oligomer with short chains, a stearate, and a laurate, or from a combination of at least two thereof. An exemplary silicon oligomer with short chains has a viscosity in a range from 5.Math.10-4 to 100.Math.10-4 m.sup.2/s.

(32) Polyalkylsiloxanes

(33) In the context of the invention, any polyalkylsiloxane which the skilled person knows and deems appropriate for any of the purposes of the invention comes into consideration for the particles of the plurality of particles of the hollow bodies provided according to the invention, and for the first and further plurality of particles of the process provided according to the invention, as well as for the plurality of particles of the use provided according to the invention. An exemplary polyalkylsiloxane is a polymethylsiloxane. An exemplary polymethylsiloxane is a polydimethylsiloxane (PDMS). An exemplary polymethylsiloxane is polysilsesquioxane.

(34) Depyrogenation

(35) The heating in the process step d) of the process or the heating prior the process step B) of the process or both may be a measure of a depyrogenation step. In the technical field of pharmacy, depyrogenation is a step of decreasing an amount of pyrogenic germs on a surface, such as via a heat-treatment. Therein, the amount of pyrogenic germs on the surface may be decreased as much as possible, such as by at least 80%, at least 90%, at least 95%, at least 99%, at least 99.5%, or by 100%, in each case based on an amount of the pyrogenic germs on the surface prior to the depyrogenation.

(36) Pharmaceutical Composition

(37) In the context of the invention, every pharmaceutical composition which the skilled person deems suitable comes into consideration. A pharmaceutical composition is a composition comprising at least one active ingredient. An exemplary active ingredient is a vaccine. The pharmaceutical composition may be fluid or solid or both. An exemplary solid composition is granular such as a powder, a multitude of tablets or a multitude of capsules. A further exemplary pharmaceutical composition is a parenteral, i.e. a composition which is intended to be administered via the parenteral route, which may be any route which is not enteral. Parenteral administration can be performed by injection, e.g. using a needle (usually a hypodermic needle) and a syringe, or by the insertion of an indwelling catheter.

(38) Wall

(39) Herein, the wall of the hollow body comprises a layer of glass. The wall may comprise further layers on one or both sides of the layer of glass. The layer of glass may extends laterally throughout the wall. This means that each point on the wall surface lies on top of a point of the layer of glass. The hollow body may be a hollow body of glass. In any case, the layers of the wall are joined to one another. Two layers are joined to one another when their adhesion to one another goes beyond Van-der-Waals attraction forces. The particles of the plurality of particles, however, may be joined to the layer of glass through Van-der-Waals attraction forces, or covalent bonds, or both.

(40) Unless otherwise indicated, the components of the wall, in particular layers and particles, may follow one another in a direction of a thickness of the wall indirectly, in other words with one or at least two intermediate components, or directly, in other words without any intermediate component. This is particularly the case with the formulation wherein one component, for example particles, superimposes another, for example the layer of glass. Further, if a component is superimposed onto a layer or a surface, this component may be contacted with that layer or surface or it may not be contacted with that layer or surface, but be indirectly overlaid onto that layer or surface with another component (e.g. a layer) in-between.

(41) Alkali Metal Barrier Layer and Hydrophobic Layer

(42) In some embodiments, the layer of glass of the hollow body is superimposed by an alkali metal barrier layer or by a hydrophobic layer or both, in each case towards the interior volume of the hollow body. The alkali metal barrier layer or by the hydrophobic layer or both may form at least a part of the interior surface, such as the full interior surface. The alkali metal barrier layer may consist of any material or any combination of materials which the skilled person deems suitable for providing a barrier action against migration of an alkali metal ion, such as against any alkali metal ion. The alkali metal barrier layer may be of a multilayer structure. In some embodiments, the alkali metal barrier layer comprises SiO.sub.2, such as a layer of SiO.sub.2. Further, the hydrophobic layer may consist of any material or any combination of materials which provides a layer surface towards the interior volume which has a contact angle for wetting with water of more than 90°. The hydrophobic layer may allow for the formation of a well-defined cake upon freeze-drying, in particular in terms of a shape of the cake. An exemplary hydrophobic layer comprises a compound of the general formula SiO.sub.xC.sub.yH.sub.z, such as a layer of this compound. Therein, x is a number which is less than 1, such as in a range from 0.6 to 0.9 or from 0.7 to 0.8; y is a number in a range from 1.2 to 3.3, such as from 1.5 to 2.5; and z is a number as well.

Measurement Methods

(43) The following measurement methods are to be used in the context of the invention. Unless otherwise specified, the measurements have to be carried out at an ambient temperature of 23° C., an ambient air pressure of 100 kPa (0.986 atm) and a relative atmospheric humidity of 50%.

(44) Contact Angle for Wetting with Water

(45) The contact angle of a surface for wetting with water is determined in accordance with the standard DIN 55660, parts 1 and 2. The contact angle is determined using the static method. Deviating from the standard, the measurement is conducted at curved surfaces as the wall of the hollow body is usually curved. Further, the measurements are conducted at 22 to 25° C. ambient temperature and 20 to 35% relative atmospheric humidity. A Drop Shape Analyzer—DSA30S from Krüss GmbH is applied for the measurements. Uncertainty of the measurement increases for contact angles below 10°.

(46) Wall Thickness and Tolerance of Wall Thickness

(47) The wall thickness and deviations from the mean value of the wall thickness (tolerance) are determined in accordance with the following standards for the respective type of hollow body:

(48) DIN ISO 8362-1 for vials,

(49) DIN ISO 9187-1 for ampoules,

(50) DIN ISO 110 4 0-4 for syringes,

(51) DIN ISO 13926-1 for cylindrical cartridges, and

(52) DIN ISO 11040-1 for dental cartridges.

(53) Transmission Coefficient

(54) Herein, the transmission coefficients are defined as T=I.sub.trans/I.sub.0, wherein I.sub.0 is the intensity of the light which is incident at a right angle on an incidence region of the surface region and I.sub.trans is the intensity of the light which leaves the hollow body on a side of the hollow body which is opposite to the incidence region. Hence, T refers to light which transmits the empty hollow body completely, i.e. one time through the wall into the empty interior volume and from there a second time through the wall out of the interior volume. Hence, the light transmits through two curved sections of the wall of the hollow body. The transmission coefficient is determined in accordance with the standard ISO 15368:2001(E), wherein an area of measurement of the dimensions 3 mm×4 mm is used. Further, the light is incident on the hollow body at a right angle to the vertical extension of the exterior surface of the hollow body. In some embodiments, the transmission coefficients herein refer to a hollow body of the type 2R according to DIN/ISO 8362 and to a transmission of the light through a part of the hollow body which is of the shape of a hollow cylinder. In case the transmission coefficient for a transmission of light via an unfunctionalized surface of a hollow body (herein also referred to as first transmission coefficient) is to be determined and the hollow body does not have any unfunctionalized surface which is suitable for the measurement, the functionalization (e.g. particles) is removed first and then the transmission coefficient via the surface from which the functionalization has been removed is determined.

(55) Haze

(56) The haze is a measure for the light scattering properties of a transparent sample, such as a glass sample. The value of the haze represents the fraction of light which has been transmitted through the sample, here the empty container, and which is scattered out of a certain spatial angle around the optical axis. Thus, the haze quantifies material defects in the sample which negatively affect transparency. Herein, the haze is determined according to the standard ASTM D 1033. In accordance with this standard, 4 spectra are measured and for each of them the transmission coefficient is calculated. The haze value in % is calculated from these coefficients of transmission. A Thermo Scientific Evolution 600 spectrometer with integrating sphere and the software OptLab-SPX are applied for the measurements. In order to allow for measuring the diffusive transmission, the sample is positioned in front of the entrance of the integrating sphere. The reflection opening is left empty such that only the transmitted and scattered fraction of the incident light is detected. The fraction of the transmitted light which is not sufficiently scattered is not detected. Further measurements pertain to detection of the scattered light in the sphere (without sample) and to the overall transmission of the sample (reflection opening closed). All the measurement results are normalized to the overall transmission of the sphere without sample which is implemented as obligatory baseline correction in the software. Herein, the haze refers to light which transmits the hollow body completely, i.e. one time through the wall into the interior volume and from there a second time through the wall out of the interior volume. Hence, the light transmits through two curved sections of the wall of the hollow body. Further, the light is incident on the hollow body at a right angle to the vertical extension of the exterior surface of the hollow body. The hollow body may be a vial of the type 2R according to DIN/ISO 8362 and the transmission is conducted through a part of the hollow body which is of the shape of a hollow cylinder. In case the haze for a transmission of light via an unfunctionalized surface of a hollow body (herein also referred to as first haze) is to be determined and the hollow body does not have any unfunctionalized surface which is suitable for the measurement, the functionalization (e.g. particles) is removed first and then the haze via the surface from which the functionalization has been removed is determined.

(57) Scratch Test and Coefficient of Dry Sliding Friction

(58) An MCT MikroCombiTester (MCT S/N 01-04488) from CSM Instruments is applied for the scratch test and for measuring the coefficient of dry friction. As the friction partner, a hollow body which is identical to the hollow body to be tested, including any coatings or functionalizations, is used. Further, in the test same surfaces are scratched/slide against each other. The friction partner is hold in position by a special mount above the hollow body to be tested. Here, the friction partner and the hollow body to be tested incline an angle of 90° in a top view. For both measurements, the hollow body to be tested is moved forwards, thereby scratching over the surface of the friction partner at a well-defined normal force (test force). For both tests, the hollow body to be measured is moved forwards underneath the friction partner at a velocity of 10 mm/min over a test length of 15 mm. In case of the scratch test, the test force is progressively increased from 0 to 30 N (load rate 19.99 N/min) across the test length. Afterwards, the scratched surface is checked with a microscope at a magnification of 5 times. In case of measuring the coefficient of dry sliding friction, a constant normal force of 0.5 N is applied. The lateral friction force is measured using the friction measuring table. The coefficient of dry friction is determined from the measured curves as the ratio of friction force to normal force (test force), wherein only values after the initial 0.2 mm up to the full test length of 15 mm are considered, in order to minimise the influence of the static friction.

(59) Cover Ratio

(60) Here, a topographical measurement of the surface to be studied is conducted with a white-light-spectrometer of the type Coherence Scanning Interferometry/Phase Shift Interferometry (CSI/PSI) from Zygo Corporation. The cover ratio is calculated from the obtained topographical image. The sum of the elevated areas is divided by the total area of measurement.

(61) Particle Size Distribution

(62) The particle size distribution is determined by dynamic light scattering (DLS). A Delsa™ Nano HC from Beckman Coulter is applied for the measurement. A sample of about 1 ml of the particles to be studied is taken. The sample is inserted into a plastic cuvette together with a liquid medium which is suitable for obtaining a dispersion. Therein, the liquid medium is to be chosen depending on the specific particles to be studied. In particular, the liquid medium is to be chosen such that a stable dispersion can be obtained in which the particles are visible for the measurement. In the case of the polymethylsiloxane particles (Tospearls 145A from Momentive Performance Materials Inc.) used in the examples below, n-butanol is to be used as the liquid medium. If the sample is a dispersion which is very opaque, it is diluted until the laser intensity is above 10%. The sample is measured in accordance with the standard method of the measurement device as 25° C. Therein, the algorithm calculates the diameter from 850 measurements. The standard software of the measuring device creates a diagram which shows the relative intensity of the measurements versus the particle diameter. The respective arithmetic mean and the standard deviation are provided by the software as well.

(63) The aspect ratio of the particles is determined using an optical microscope or a scanning electron microscope. In each case, lengths and thicknesses of 10 arbitrarily chosen particles of the plurality of particles to be studied are measured and the arithmetic mean value is determined.

(64) The invention is set out in more detail below by reference to examples and drawings, with the examples and drawings not denoting any restriction on the invention. Furthermore, unless otherwise indicated, the drawings are not to scale.

Example 1 (According to the Invention)

(65) Preparation of the Composition:

(66) 50 g of isopropanol are provided in a beaker. 3 g of tetraethoxysilane are added to the beaker and the obtained composition is stirred for 60 s with a magnetic stirrer at ambient temperature of 20° C. Further, 3.2 g of polymethylsiloxane particles (Tospearls 145A from Momentive Performance Materials Inc.) are added. The composition is stirred for another 4 h at the ambient temperature. The thus obtained suspension is ready for use.

(67) Functionalization with the composition:

(68) A commercially available glass vial of the type “Vial 2.00 ml Fiolax clear” from Schott AG, which is further of the type 2R according to DIN/ISO 8362, is provided. The surface of this vial does not have any coating or functionalization. This vial is washed as described below. The washed vial is immersed with its bottom first into the composition, which has been prepared as set out above, at a velocity of 30 cm/min. Therein, the head region of the vial, including the vial opening, is not immersed into the composition in order to prevent contacting the interior surface of the vial with the composition. The vial is kept in the composition for about 10 s. Afterwards, the vial is retracted from the composition at a velocity of 5 cm/min. Subsequently, the vial is kept as it is for 10 s at ambient temperature of 20° C. Then the vial is placed with its bottom onto an absorbent substrate such as a paper towel. Then the composition which has been applied to the vial is dried by keeping the vial for 30 min at a temperature of 600° C. in an oven.

Example 2 (According to the Invention)

(69) Preparation of the Composition:

(70) 50 g of high purity water are provided in a beaker. 3 g of tetraethoxysilane are added to the beaker and the obtained composition is stirred for 60 s with a magnetic stirrer at ambient temperature of 20° C. Subsequently, 10 g of a polydimethylsiloxane (viscosity of 50.Math.10.sup.−4 m.sup.2/s) are added while the composition is stirred. Then, the composition is heated to 30° C. Further, 3.2 g of polymethylsiloxane particles (Tospearls 145A from Momentive Performance Materials Inc.) are added. The composition is stirred for another 4 h at 30° C. The thus obtained suspension is ready for use.

(71) Functionalization with the Composition:

(72) A commercially available glass vial of the type “Vial 2.00 ml Fiolax clear” from Schott AG, which is further of the type 2R according to DIN/ISO 8362, is provided. The surface of this vial does not have any coating or functionalization. This vial is washed as described below. The washed vial is immersed with its bottom first into the composition, which has been prepared as set out above, at a velocity of 30 cm/min. Therein, the head region of the vial, including the vial opening, is not immersed into the composition in order to prevent contacting the interior surface of the vial with the composition. The vial is kept in the composition for about 10 s. Afterwards, the vial is retracted from the composition at a velocity of 5 cm/min. Subsequently, the vial is kept as it is for 10 s at ambient temperature of 20° C. Then the vial is placed with its bottom onto an absorbent substrate such as a paper towel. Then the composition which has been applied to the vial is dried by keeping the vial for 10 min at a temperature of 350° C. in an oven.

Example 3 (According to the Invention)

(73) Preparation of the Composition:

(74) 50 g of high purity water are provided in a beaker. 3 g of tetraethoxysilane are added to the beaker and the obtained composition is stirred for 60 s with a magnetic stirrer at ambient temperature of 20° C. Subsequently, 10 g of a polydimethylsiloxane (viscosity of 50.Math.10.sup.−4 m.sup.2/s) are added while the composition is stirred. Then, the composition is heated to 30° C. Further, 3.2 g of polymethylsiloxane particles (Tospearls 145A from Momentive Performance Materials Inc.) and 0.5 g of the dispersing agent DISPERBYK-103 which is available from BYK-Chemie GmbH, Wesel, Germany are added. The composition is stirred for another 4 h at 30° C. The thus obtained suspension is ready for use.

(75) Functionalization with the Composition:

(76) A commercially available glass vial of the type “Vial 2.00 ml Fiolax clear” from Schott AG, which is further of the type 2R according to DIN/ISO 8362, is provided. The surface of this vial does not have any coating or functionalization. This vial is washed as described below. The washed vial is immersed with its bottom first into the composition, which has been prepared as set out above, at a velocity of 30 cm/min. Therein, the head region of the vial, including the vial opening, is not immersed into the composition in order to prevent contacting the interior surface of the vial with the composition. The vial is kept in the composition for about 10 s. Afterwards, the vial is retracted from the composition at a velocity of 5 cm/min. Subsequently, the vial is kept as it is for 10 s at ambient temperature of 20° C. Then the vial is placed with its bottom onto an absorbent substrate such as a paper towel. Then the composition which has been applied to the vial is dried by keeping the vial for 10 min at a temperature of 350° C. in an oven.

Comparative Example 1 (not According to the Invention)

(77) A commercially available glass vial of the type “Vial 2.00 ml Fiolax clear” from Schott AG, which of the type 2R according to DIN/ISO 8362, is provided as a reference. The surface of this vial does not have any coating or functionalization.

Comparative Example 2 (not According to the Invention)

(78) A commercially available glass vial of the type “Vial 2.00 ml Fiolax clear” from Schott AG, which of the type 2R according to DIN/ISO 8362, is coated on its exterior surface with MED10-6670 from NuSiL.

Comparative Example 3 (not According to the Invention)

(79) A commercially available glass vial of the type “Vial 2.00 ml Fiolax clear” from Schott AG, which is further of the type 2R according to DIN/ISO 8362, is provided. The surface of this vial does not have any coating or functionalization. This vial is washed as described below. Then the vial is placed inside a SCS Labcoater®, Model PDS 2010. Via a vacuum process, the vial is first functionalized with 3-methacrylaoxypropyltrimethoxysilane by evaporation without further heat treatment and then coated with Parylen C by evaporation at 100° C. The final coating has a film thickness of 250 nm.

Comparative Example 4 (not According to the Invention)

(80) Preparation of the Composition:

(81) 99.8 ml of high purity water are provided in a beaker. 0.2 ml of Levasil CS50-34P (50% SiO.sub.2, average particle size less than 100 nm) from Akzo Nobel N.V. are added to the beaker and the obtained composition is stirred for 30 s with a magnetic stirrer at ambient temperature of 20° C. Subsequently, 0.5 ml g of Tween20 from Sigma Aldrich are added. Then, the composition is stirred for another 10 min. The thus obtained composition is ready for use.

(82) Functionalization with the Composition:

(83) A commercially available glass vial of the type “Vial 2.00 ml Fiolax clear” from Schott AG, which is further of the type 2R according to DIN/ISO 8362, is provided. The surface of this vial does not have any coating or functionalization. This vial is washed as described below. The washed vial is immersed with its bottom first into the composition, which has been prepared as set out above, at a velocity of 30 cm/min. Therein, the head region of the vial, including the vial opening, is not immersed into the composition in order to prevent contacting the interior surface of the vial with the composition. The vial is kept in the composition for 2 s. Afterwards, the vial is retracted from the composition at a velocity of 20 cm/min. Subsequently, the vial is kept as it is for 10 s at ambient temperature of 20° C. Then the vial is placed with its bottom onto an absorbent substrate such as a paper towel. Then the composition which has been applied to the vial is dried by keeping the vial for 30 min at a temperature of 600° C. in an oven.

(84) Evaluation

(85) For each of the examples 1 to 3 and the comparative examples 1 to 4, the contact angle for wetting with water and the coefficient of dry sliding friction are determined on the exterior surface of the vial body in accordance with the above measurement methods, respectively. The results are shown in Table 1.

(86) TABLE-US-00001 TABLE 1 Characterization of the exterior surfaces of the glass vials of the examples and comparative examples by their contact angles for wetting with water and coefficients of dry sliding friction, in each case prior to any post treatment. Contact angle for Coefficient of dry sliding Example water [°] friction Example 1 34 0.01 Example 2 26 0.18 Example 3 43 0.20 Comparative example 1 <10 0.5 Comparative example 2 70 0.28 Comparative example 3 93 0.45 Comparative example 4 <10 0.41

(87) Further, 10,000 Of the vials of each example and comparative example, respectively, are processed on a standard pharmaceutical filling line and thus, filled with an influenza vaccine. Table 2 below shows an evaluation of the vials regarding their tendency to be damaged or even break on the filling line. Here, ++ means that no or only very few vials are being damaged or broken, + means that few vials are being damaged or broken, − means that damages to vials and broken vials occur more often than for +, −− means that damages to vials and broken vials occur more often than for −.

(88) TABLE-US-00002 TABLE 2 Comparison of the tendency of the glass vials to be damaged on the filling line for the examples and comparative examples Example Low tendency to damages on filling line Example 1 ++ Example 2 + Example 3 + Comparative example 1 −− Comparative example 2 − Comparative example 3 − Comparative example 4 −−

(89) Further, the vials of the examples and of the comparative example 1 are studied for their optical characteristics which may influence an optical inspection of the vials, in particular for pharmaceutically relevant particles, after being filled with a vaccine and being closed. These studies are conducted prior to filling the vials. Here, the increase of the haze by the functionalizations of the examples 1 to 3 is determined in accordance with the above measurement method to be less than 0.3% of the haze of an unfunctionalized reference vial of comparative example 1. Further, the transmission coefficients of vials of the examples 1 to 3 and of a reference vial of comparative example 1 are determined in accordance with the above measurement method. FIG. 11 shows the transmission coefficients of empty vials of the examples 1 to 3 and of comparative example 1 across a broad spectral range. From this figure, it can clearly be seen that the functionalizations according to the examples 1 to 3 do not significantly deteriorate the transmission coefficient in the studied spectral range.

(90) For further studies, functionalized surfaces of vials according to the examples 1 to 3 and the comparative example 1 have been subjected to a scratch test which is described in detail in the above measurement methods sections. It has been shown that the vials according to the examples 1 to 3 show an improvement of their scratch resistance with respect to the reference vial of comparative example 1 at least up to test forces of 5 N.

(91) Post-Treatment

(92) For further studies, the vials of the examples 1 and 2 and of the comparative example 1 as reference are subjected to three different kinds of post-treatment, i.e. a washing procedure, a depyrogenation procedure and a freeze drying. These kinds of post-treatment are described below. The washing procedure is the same as used prior to functionalizing/coating the vials in the examples 1 to 3 and of the comparative examples 2 to 4. Also the reference vial of comparative example 1 has been washed as described below.

(93) Washing:

(94) A HAMO LS 2000 washing machine is applied for the washing procedure. The HAMO LS 2000 is connected to the purified water supply. Further, the following devices are used.

(95) cage 1: 144 with 4 mm nozzles

(96) cage 2: 252 with 4 mm nozzles drying cabinet from Heraeus (adjustable up to 300° C.)

(97) The tap is opened. Then the machine is started via the main switch. After conducting an internal check, the washing machine shows to be ready on the display. Program 47 is a standard cleaning-program which operates with the following parameters:

(98) pre-washing without heating for 2 min

(99) washing at 40° C. for 6 min

(100) pre-rinsing without heating for 5 min

(101) rinsing without heating for 10 min

(102) end-rinsing at without heating for 10 min

(103) drying without heating for 5 min

(104) The holder for the vials in the cages 1 and 2 have to be adjusted considering the size of the vials in order to obtain a distance of the nozzle of about 1.5 cm. The vials to be washed are placed on the nozzles with the head first. Subsequently, the stainless steel mesh is fixed on the cage. The cage is oriented to the left and pushed into the machine. Then the machine is closed. Program 47 (GLAS040102) is selected and then the HAMO is started via START. After the program has finished (1 h), the cages are taken out and the vials are placed with their opening facing downwards in drying cages. A convection drying cabinet with ambient air filter is applied for the drying. The drying cabinet is adjusted to 300° C. The vials are placed into the drying cabinet for 20 min. After the vials have cooled down, they are sorted into appropriate boxes.

(105) Depyrogenation:

(106) The vials are depyrogenised by placing them in an oven which is heated to 350° C. This temperature is kept constant for 1 h. Subsequently, the vials are taken out of the oven and left to cool down.

(107) Freeze drying:

(108) The vials are freeze dried by storing them for 4 hours at −70° C.

(109) Evaluation after Post-Treatment

(110) Vials of the examples 1 and 2 have been subjected to various combinations of the above types of post-treatment. As a reference, vials of comparative example 1 have been subjected to the depyrogenation treatment as well.

(111) In each case, the coefficient of dry sliding friction has been determined on the exterior surfaces of the vials in their tubular body regions. The results are shown in FIG. 10. FIG. 10 compares, from left to right, the coefficients of dry sliding friction of vials of example 1 (no post-treatment, after depyrogenation), example 2 (no post-treatment, after depyrogenation, after freeze drying, after washing, after washing and depyrogenation) and of comparative example 1 (no post-treatment, after depyrogenation). It is demonstrated that the functionalizations of examples 1 and 2 withstand the washing procedure as well as the depyrogenation procedure and the freeze drying.

(112) For further studies, vials according to the examples 1 to 3 have been washed as described above. Then the washed vials have been broken such that the interior surfaces became accessible for measurements of the contact angle for wetting with water. Those measurements have been conducted at 5 different positions (1 to 5) on the interior surface which are depicted schematically in FIG. 8. The measurement results for vials of example 1 are shown in FIG. 9.

(113) Even further tests have been conducted, in that vials according to the examples 1 to 3 have been freeze dried. Prior to and after this procedure the functionalized surfaces have been checked for damages and defects under the microscope at a magnification of 5 to 20 times. It has been observed that no defects or damages have been caused by the freeze-drying procedure. FIG. 14 shows the exterior surface of a vial of example 2 prior to freeze-drying and FIG. 15 after freeze drying. No damages or defects are observed.

(114) FIG. 1 shows a schematic depiction of an exemplary embodiment of a hollow body 100 provided according to the invention. The hollow body 100 comprises a wall 102 which partially surrounds an interior volume 101 of the hollow body 100. The wall 102 surrounds the interior volume 101 only partially in that the hollow body 100 comprises an opening 107 which allows for filling the hollow body 100 with a pharmaceutical composition 301 (not shown). The wall 102 forms from top to bottom in the FIG. 1: a top region of the hollow body 100, which consists of a flange 108 and a neck 109; a body region 111, which follows the top region via a shoulder 110; and a bottom region 113, which follows the body region 111 via a heel 112. Here, the body region 111 is a lateral region of the hollow body 100 in form of a hollow cylinder. The wall 102 comprises a layer of glass 104 and a wall surface 103, wherein the layer of glass 104 extends across the full area of the wall surface 103. The wall surface 103 consists of an interior surface 106 which faces the interior volume 101, and an exterior surface 105 which faces away from the interior volume 101. Here, the part of the exterior surface 105 which lies in the body region 111 of the hollow body 1100 forms a surface region of the wall surface 103, which is characterized by a coefficient of dry sliding friction of 0.02.

(115) FIG. 2 illustrates a schematic depiction of a further hollow body 100 provided according to the invention.

(116) The hollow body 100 of FIG. 2 is a vial which has been obtained in accordance with example 1 according to the invention as explained above. This vial is of the same shape as the hollow body 100 of FIG. 1. Deviating from FIG. 1, the vial of FIG. 2 has a coefficient of dry sliding friction of 0.01 across its exterior surface 105. Moreover, a plurality of spherical particles 201 is directly joined to the layer of glass 104 across the exterior surface 105 of the wall 102. The particles 201 are SiO.sub.2-particles which have been obtained from the PDMS-particles which have been applied to the exterior surface 105 of the vial according to example 1.

(117) FIG. 3 illustrates a schematic depiction of an exemplary embodiment of a closed hollow body 300 provided according to the invention which is also a closed container 300 according to the invention. Further, this closed container 300 is a vial which has been obtained by filling the hollow body 100 of FIG. 2 with a pharmaceutical composition 301 and closing the opening 107 with a lid 302 via a crimping step. Here, the pharmaceutical composition 301 is a vaccine.

(118) FIG. 4 illustrates a flow chart of an exemplary embodiment of a process 400 provided according to the invention for the preparation of a hollow body 100. The process 400 comprises a process step a) 401 in which a commercially available glass vial of the type “Vial 2.00 ml Fiolax clear” from Schott AG which of the type 2R according to DIN/ISO 8362 is provided. A process step b) 402 of partially superimposing a layer of glass 104 of the vial with a composition is conducted as described above for example 1. Accordingly, the composition comprises isopropanol as vehicle and a plurality of PDMS-particles 201. Also the step c) 403 of decreasing a proportion of the isopropanol in the composition is conducted as described in the context of example 1. Thereby, the hollow body 100 of FIG. 2 is obtained, in which SiO.sub.2-particles are joined to the layer of glass 104 across the full exterior surface 105 of the vial.

(119) FIG. 5 illustrates a flow chart of another exemplary embodiment of a process 500 provided according to the invention for the preparation of a hollow body 100. The process 500 of FIG. 5 comprises the process steps a) 401 to c) 403 of the process 400 according to FIG. 4 and further, a process step d) 501 of depyrogenising the hollow body 100 in accordance with the above described depyrogenation process.

(120) FIG. 6 illustrates a flow chart of an exemplary embodiment of a process 600 provided according to the invention for packaging a pharmaceutical composition 301. In a process step A) 601, the hollow body 100 according to FIG. 2 is provided. In a process step B) 602, a pharmaceutical composition 301 is filled into the interior volume 101 of the hollow body 100, and in a process step C) 603 the opening 107 of the hollow body 100 is closed, thereby obtaining the closed hollow body 300 of FIG. 3.

(121) FIG. 7 illustrates a flow chart of an exemplary embodiment of a process 700 provided according to the invention for treating a patient. The process 700 comprises the process steps of: A. 701 providing the closed hollow body 300 of FIG. 3, opening the closed hollow body 300 by penetrating the lid 302 with a needle of a syringe, filling the syringe with the vaccine; and B. 702 administering the vaccine subcutaneously to a patient using the syringe.

(122) FIG. 8 illustrates a schematic depiction of the positions 1 to 5 on the interior surface 106 of vials at which the contact angle for wetting with water has been measured in the studies of contamination of the interior surface 106 due to a washing process.

(123) FIG. 9 illustrates results of the studies of contamination of the interior surface 106 due to a washing process for vials of example 1. Here, the contact angle 901 for wetting with water is plotted for each position 1 to 5. At the positions 3 to 4, the contact angle 901 is below 10° (similar to the reference comparative example 1, see Table 1 above). This shows that the interior surface 106 has not been contaminated with the SiO.sub.2-particles which have been obtained on the exterior surface 105 from the PDMS-particles due to the washing process.

(124) FIG. 10 illustrates a diagram with results of measurements of the coefficient of dry sliding friction 1001 of vials of examples 1 and 2 and comparative example 1. Here, bar 1002 shows the result for vials of example 1 without any post-treatment. Bar 1003 shows the results for vials of example 1 after the vials have been depyrogenised as outlined above. Bars 1004 to 1008 show results for vials of example 2, from left to right: bar 1004 without any post-treatment, bar 1005 after depyrogenation, bar 1006 after freeze drying, bar 1007 after washing only, bar 1008 after washing and subsequent depyrogenation. Bar 1009 shows the results for vials of comparative example 1 after washing the vials and bar 1010 shows the results for vials of comparative example 1 after washing and depyrogenising them.

(125) FIG. 11 illustrates results of measurements of the transmission coefficient 1102 of vials according to the examples 1 to 3 and the comparative example 1 over the wavelength in nm 1101. In the diagram, 1103 denotes the measurement results for the examples 1 to 3 and comparative example 1. All these results are so close to each other that the corresponding graphs appear as one in the diagram. The dip at 865 nm is a measurement artefact.

(126) FIG. 12 illustrates a microscope image of the exterior surface 105 of a vial according to example 1. The image has been obtained using the following parameters: acceleration voltage (EHT)=5.99 kV, working distance (WD)=6.9 mm, magnification=1.00 k X. The plurality of particles 201 can clearly be seen on the layer of glass 104.

(127) FIG. 13 illustrates a further microscope image of the exterior surface 105 of a vial according to example 1. The image has been obtained using the following parameters: acceleration voltage (EHT)=5.00 kV, working distance (WD)=7.0 mm, magnification=5.00 k X. The plurality of particles 201 can clearly be seen on the layer of glass 104. The diameters of two exemplary particles are shown in the figure to be at 3.292 μm and 3.704 μm, respectively.

(128) FIG. 14 illustrates a microscope image of the exterior surface 105 of a vial according to example 2 prior to freeze drying. The plurality of particles 102 can be seen on the layer of glass 104.

(129) FIG. 15 illustrates a microscope image of the exterior surface of the vial according to example 2 of FIG. 14 after freeze-drying. The plurality of particles 102 can be seen on the layer of glass 104. No defects or damages from the freeze-drying are visible.

(130) While this invention has been described with respect to at least one embodiment, the present invention can be further modified within the spirit and scope of this disclosure. This application is therefore intended to cover any variations, uses, or adaptations of the invention using its general principles. Further, this application is intended to cover such departures from the present disclosure as come within known or customary practice in the art to which this invention pertains and which fall within the limits of the appended claims.

LIST OF REFERENCE NUMERALS

(131) 100 hollow body according to the invention 101 interior volume 102 wall 103 wall surface 104 layer of glass 105 exterior surface 106 interior surface 107 opening 108 flange 109 neck 110 shoulder 111 body region 112 heel 113 bottom region 201 particles of plurality of particles 300 closed container according to the invention/closed hollow body according to the invention 301 pharmaceutical composition 302 lid 400 process according to the invention for the preparation of a hollow body 401 process step a) 402 process step b) 403 process step c) 500 process according to the invention for the preparation of a hollow body 501 process step d) 600 process according to the invention for packaging a pharmaceutical composition 601 process step A) 602 process step B) 603 process step C) 700 process according to the invention for treating a patient 701 process step A. 702 process step B. 901 contact angle for wetting with water in ° 1 to 5 positions of measurement of the contact angle for wetting with water on the interior surface after the washing procedure 1001 coefficient of dry sliding friction 1002 measurement results for example 1 without post-treatment 1003 measurement results for example 1 after depyrogenation 1004 measurement results for example 2 without post-treatment 1005 measurement results for example 2 after depyrogenation 1006 measurement results for example 2 after freeze drying 1007 measurement results for example 2 after washing without further post-treatment 1008 measurement results for example 2 after washing and depyrogenation 1009 measurement results for comparative example 1 after washing without further post-treatment 1010 measurement results for comparative example 1 after washing and depyrogenation 1101 wavelength in nm 1102 transmission coefficient 1103 measurement results for examples 1 to 3 and comparative example 1