description
FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
As amended by the Patents (Amendment) Act, 2005
&
The Patents Rules, 2003
As amended by the Patents (Amendment) Rules, 2006
COMPLETE SPECIFICATION
(See section 10 and rule 13)
TITLE OF THE INVENTION
CONTAINER MADE OF BOROSILICATE GLASS WITH IMPROVED
CHEMICAL RESISTANCE FOR A PHARMACEUTICAL OR
DIAGNOSTIC SUBSTANCE
APPLICANT
SGD S.A., a French company, having its address at Tour Cb 16 17 Place des
Reflets 92097 Paris La Défense Cédex, France
PREAMBLE TO THE DESCRIPTION
The following specification particularly describes the nature of this invention
and the manner in which it is to be performed:
2
TECHNICAL FIELD
The present invention relates to the general technical field of glass containers, in
5 particular for the packaging of pharmaceutical or diagnostic substances.
PRIOR ART
In the field of pharmaceutical glass primary packaging, the purpose is to propose
containers, in particular of the vial type, that have an excellent chemical compatibility with
the product or preparation they are intended to contain. Indeed, the aim is to prevent any
10 harmful interaction between a species from the glass forming the container and the
product contained by the latter.
In this context, the pharmacopoeias identify three main different types of glass containers,
which may be acceptable for a pharmaceutical use according to the nature of the
considered preparation. These containers are classified according to their level of
15 chemical resistance, i.e. according to the resistance shown by the glass, of which they
are formed, to the transfer of water-soluble inorganic substances in determined conditions
of contact between the surface of the considered glass container and the water. A
distinction is made between the borosilicate glass containers, said of "Type I", which have
intrinsically an excellent chemical resistance and which thus suit for most pharmaceutical
20 substances and preparations, and the conventional soda-lime-silica glass containers,
said of "Type III", whose chemical resistance is far less advantageous. That way, the use
of these latter is limited to non-aqueous vehicle preparations for parenteral use, to the
powders for parenteral use (except freeze-dried preparations) and to the preparations for
non-parenteral use. A distinction is also made between so-called "Type II" glass
25 containers, which are conventional soda-lime-silica glass containers, like the Type III
ones, but whose inner face has been subjected to a specific surface treatment in order to
significantly improve their hydrolytic resistance. Type II glass containers thus have an
intermediate chemical resistance between those of the Type II glass containers and the
3
Type I glass containers, which make them suitable for packaging most of the acid and
neutral aqueous preparations.
In view of the above, Type I glass is considered, in pharmaceutical industry, as the most
chemically resistant glass. It is therefore the glass of choice for storing the most
5 aggressive or the most unstable solutions. However, in some particular cases, even Type
I glass formulation proves insufficiently chemically resistant for storing pharmaceutical
solutions. The Type I glass surface may be corroded and attacked, therefore releasing
significant concentrations of extractable species from the glass. It is commonly accepted
that, for example, the storage of Water for Injection (WFI) is difficult, even in Type I glass
10 containers. As regards the release of glass extractables in solution, and in addition to
sodium, certain trace elements such as barium, zinc, aluminium, boron, lead, etc. can
pose significant health problems. These elements are indicated in the ICHQ3D
("International Conference on Harmonization") information documentation as potentially
presenting a risk to the patient's health if administered by parenteral injection.
15 That is why it has been contemplated to cover the inner face of the glass wall of the
borosilicate glass containers with a barrier coating, for example made of pure silica SiO2
or silicone-based, in order to further improve the chemical resistance thereof.
Nevertheless, the implementation of such a barrier coating makes the manufacturing of
the containers more complex and more expensive. Moreover, it does not always provide
20 the containers with a sufficient chemical resistance, depending on the nature of the
substances they are intended to contain.
DISCLOSURE OF THE INVENTION
As a result of the foregoing, the objects assigned to the present invention aim to remedy
the technical shortcomings and problems identified hereinabove, and to propose a new
25 glass wall container having an excellent chemical resistance while being relatively
inexpensive to manufacture.
Another object of the invention aims to propose a new glass wall container that is
moreover particularly easy to manufacture.
4
Another object of the invention aims to propose a new glass wall container that is safe in
terms of health.
The objects assigned to the invention are achieved by means of a container comprising
a glass wall delimiting an accommodation cavity for a substance, in particular for a
5 pharmaceutical or diagnostic substance, said glass wall having an inner face located
facing said accommodation cavity, said container being characterized in that said wall is
made of borosilicate glass, said inner face forming a bare glass surface intended to come
into direct contact with said substance, said glass wall having an atomic fraction of
sodium, as measured by X-ray induced photoelectron spectrometry, that is lower than or
10 equal to 2.0 at.% up to a depth of at least 300 nm from the surface of the inner face.
The objects assigned to the invention are also achieved by means of a raw container
intended to form such a container according to the invention, said raw container
comprising a glass wall delimiting an accommodation cavity, said glass wall having an
inner face located facing said accommodation cavity, said wall being made of borosilicate
15 glass, said inner face forming a glass surface provided with sodium sulphate grains
shaped and arranged in a substantially uniform manner on said surface, thus forming a
substantially homogeneous translucent white bloom, said raw container being intended
to undergo a washing of the surface of the glass wall inner face in order to eliminate said
bloom.
20 BRIEF DESCRIPTION OF THE DRAWINGS
Other features and advantages of the invention will appear in more detail upon reading
of the following description, with reference to the appended drawing briefly described
hereinafter, given by way of purely illustrative and non-limiting examples.
Figure 1 schematically illustrates, in vertical cross-section, a preferential embodiment of
25 a container according to the invention, wherein the container forms a vial or a bottle.
WAYS TO IMPLEMENT THE INVENTION
The invention relates to a container 1 comprising a glass wall 2 delimiting an
accommodation cavity 3 for a substance (or product) intended to be packaged, stored,
5
within the container 1. The container 1 according to the invention thus forms a primary
packaging for said substance. The glass wall 2 of the container 1 has an inner face 4,
located facing the accommodation cavity 3, and an opposite outer face 5. Preferably, the
container 1 according to the invention forms a vial or a bottle, as in the preferential
5 embodiment illustrated as an example in Figure 1. The glass wall 2 of the container 1 is
thus advantageously formed by a glass bottom 6, by means of which the container 1 can
rest stably on a flat support, a lateral glass wall 7 that rises from the periphery of the
bottom 6, and a neck 8 provided with a ring 9 that delimits an opening 10 providing access
to the accommodation cavity 3 from the outside of the container 1. The container 1 thus
10 advantageously forms a single, monolithic piece of glass. Advantageously, said opening
10 is designed so as to be able to be closed by a removable or pierceable plug or
membrane seal (not illustrated). The substance that the container 1 according to the
invention is intended to contain within its accommodation cavity 3 is, in particular, a
pharmaceutical substance, such as for example a medication, potentially intended to be
15 administered by parenteral route (general or locoregional) or to be ingested or absorbed
by a patient, or also a diagnostic substance, as for example a chemical or biological
reagent. It is preferably a liquid substance. By extension, the container 1 can be designed
to contain a biological substance (or body fluid), such as for example blood, a blood
product or by-product, urine, etc. Preferably, the container 1 according to the invention
20 has a rated volume between 3 mL and 1 000 mL, which makes it particularly suitable for
the packaging of pharmaceutical or diagnostic substances. Even if the application to the
pharmaceutical and diagnostic fields is preferred, the invention is however not limited to
pharmaceutical and diagnostic containers and may in particular also relate to a container
designed to contain a liquid, pasty or powder substance for industrial (storage of chemical
25 products, etc.), veterinary, food or also cosmetic use.
In the sense of the invention, the word "glass" refers to a mineral glass. More particularly,
the wall of the container 1 is generally made in mass of borosilicate glass. The glass
forming the wall 2 of the container 1 therefore advantageously comprises, on average, in
mass, between 60 % and 80 % of silicon oxide SiO2, between 0 % and 3.5 % of calcium
30 oxide CaO, between 4 % and 11 % of sodium oxide Na2O, between 1 % and 8 % of
potassium oxide K2O, between 0.5 % and 4 % of barium oxide BaO, between 7 % and
14 % of boron oxide B2O3, and 2 % and 8 % of aluminium oxide Al2O3. More
advantageously, the glass of the wall 2 of the container 1 comprises, on average, in mass,
6
between 65 % and 69 % of silicon oxide SiO2, between 0 % and 1.5 % of calcium oxide
CaO, between 6 % and 9 % of sodium oxide Na2O, between 1.5 % and 5 % of potassium
oxide K2O, between 1.5 % and 3 % of barium oxide BaO, between 11 % and 13 % of
boron oxide B2O3, and 5 % and 7 % of aluminium oxide Al2O3. The glass of the glass wall
5 2 may moreover contain additional elements such as zinc, iron, etc., preferably as traces.
The glass of the wall 2 of the container 1 is preferably transparent or translucent, in the
visible domain for human eye. It may be indifferently either a colourless glass or a
coloured glass ("yellow" or "amber" glass, for example), notably to protect substance
contained in the container 1 against the effects of light, in particular in certain wavelength
10 ranges (UV, etc.).
Preferably, the container 1 according to the invention is made of moulded glass, and not
of drawn glass (i.e. manufactured from a preform, such as a tube, made of drawn glass).
In a manner known per se, such a moulded glass container 1 can be obtained by a "blowand-blow" or "press-and-blow" process, for example using an IS machine. Indeed, it has
15 been observed that a drawn glass container suffers intrinsically, due to its forming
method, from an increased risk of delamination (that is to say a risk of detachment of
glass flakes or particles from the surface of the inner face of the container wall by
interaction of the glass with the substance contained in the container) with respect to a
moulded glass container, and in particular when the glass is borosilicate glass. Now, the
20 presence of free particles of glass in a substance, in particular a pharmaceutical
substance intended to be administered to a human being or to an animal, may have very
serious health consequences.
In accordance with the invention, the inner face 4 of the wall 2 of the container 1 forms a
bare glass surface intended to come into direct contact with said substance. In other
25 words, the inner face 4 of the glass wall 2 is devoid of any continuous surface layer
exogenous to the glass of the wall 2, which would have been deposited on the inner face
4 in order to separate the latter from the substance that the accommodation cavity 3 of
the container 1 is intended to contain. More precisely, the inner face 4 of the glass wall 2
is devoid of any additional barrier coating, exogenous to the glass of the wall 2, designed
30 to prevent the migration of one or more chemical species or elements contained in the
glass of the glass wall 2 to said substance, and vice versa. The inner face 4 of the wall 2
7
of the container 1 is therefore in particular devoid of surface layer that would be formed
of an oxide, a nitride or an oxynitride of an element chosen among the group consisted
of silicon Si, aluminium Al, titanium Ti, boron B, zirconium Zr, tantalum Ta, or a mixture
of these latter, and/or also formed of an organic material, as for example one or several
5 polysilosanes (silicone), etc. Even so, it is not excluded that the container 1 can have at
the surface of its inner face 4, and in particular upstream from a filling of the
accommodation cavity 3 with said substance, one or more chemical species exogenous
to the glass of the wall 2, insofar as theses species do not form a coating layer intended
to protect the glass of the wall 2 and the substance contained in the accommodation
10 cavity 3 against any chemical interaction between them. So devoid of barrier coating
deposited on the inner face 4 of its glass wall 2, the container 1 according to the invention
is thus relatively easy and inexpensive to manufacture.
According to the invention, and although the glass wall 2 of the container 1 is generally
formed, as already described hereinabove, of a borosilicate glass, the wall 2 has a very
15 particular atomic profile of sodium in the vicinity of the surface of its inner face 4, and over
a particular depth under said surface, which provides the container 1 with very interesting
properties in terms of chemical resistance of the glass of said wall 2 with respect to the
substance intended to be contained in said container 1. In particular, said glass wall 2 of
the container according to the invention has an atomic fraction of sodium that is lower
20 than 2.0 at.% up to a depth of at least 300 nm (+/- 1 nm) from the surface of the inner
face 4 of the wall 2. Thus, from the surface of the inner face 4 of the glass wall 2, and up
to a depth of at least 300 nm, the glass of the wall 2 has an atomic fraction of sodium that
does not exceed 2.0 at.%.
This atomic fraction, as well as all the atomic fractions which will be discussed below, is
25 measured, analysed, by X-ray induced photoelectron spectrometry (XPS).
Advantageously, the atomic fractions discussed in the present disclosure of the invention
are measured by X-ray induced photoelectron spectrometry (XPS), with a detection angle
of 90° (+/- 1°) with respect to the surface of the inner face 4, using an XPS spectrometry
hardware and software system comprising a monochromatic Al Kalpha X-ray source, with
30 a diameter of analysed area between 50 µm and 1 000 µm (and for example 400 µm),
and with a deep abrasion of the surface of the inner face 4 under a flow of argon ions,
with an energy preferentially between 0.5 keV and 5 keV (and for example 2 keV), with a
8
speed of erosion preferentially between 5 nm/min and 10 nm/min (and for example of
8.5 nm/min). Well known as such, such an XPS measurement can be made for example
using a spectrometry hardware and software system Thermo Scientific™ K-Alpha™ sold
by the ThermoFischer company, with a monochromatic Al Kalpha X-ray source, a
5 diameter of analysed area of typically 400 µm, and with a deep abrasion of the surface
under a flow of argon ions, with an energy of 2 keV, with a speed of erosion (measured
on a layer of SiO2) of 8.5 nm/min, for example.
The value of atomic fraction of sodium, up to a depth of at least 300 nm, being thus at
most equal to 2 at.%, it is still more advantageous that said atomic fraction of sodium is
10 lower than or equal to 1.8 at.%, preferably lower than or equal to 1.6 at.%, preferably
lower than or equal to 1.4 at.%, and still preferably lower than or equal to 1.5 at.%, up to
a depth of at least 300 nm from the surface of the inner face 4.
The profile of atomic fraction of sodium of the glass of the wall 2 over such a depth of
300 nm is not necessarily strictly homogeneous at any depth between 0 nm and 300 nm.
15 In particular, given the generally gradual nature over time of an attack on the glass by a
substance contained in the accommodation cavity 3, it is advantageous in terms of
chemical resistance of the glass that the atomic fraction of sodium is, on average, of a
value that decreases from the inside, i.e. from the very heart, of the glass wall 2 towards
the surface of the inner face 4 of the latter.
20 Preferably, said atomic fraction of sodium of the glass of the wall 2 is lower than or equal
to 1.6 at.%, preferably lower than or equal to 1.5 at.%, preferably lower than or equal to
1.4 at.%, preferably lower than or equal to 1.3 at.%, and still preferably lower than or
equal to 1.2 at.%, up to a depth of at least 200 nm (+/- 1 nm) from the surface of the inner
face 4.
25 As an alternative or a complement, said atomic fraction of sodium of the glass of the wall
2 is lower than or equal to 1.0 at.%, preferably lower than or equal to 0.9 at.%, and still
preferably lower than or equal to 0.8 at.%, up to a depth of at least 100 nm (+/- 1 nm)
from the surface of the inner face 4.
9
As an alternative or a complement, said atomic fraction of sodium of the glass of the wall
2 is lower than or equal to 0.8 at.%, and preferably lower than or equal to 0.7 at.%, up to
a depth of at least 30 nm (+/- 1 nm) from the surface of the inner face 4. As an alternative
or a complement, said atomic fraction of sodium of the glass of the wall 2 is lower than or
5 equal to 0.5 at.%, preferably lower than or equal to 0.4 at.%, preferably lower than or
equal to 0.3 at.%, and still preferably lower than or equal to 0.2 at.%, up to a depth of at
least 10 nm (+/- 1 nm) from the surface of the inner face 4. Therefore, the glass of the
wall 2 of the container 1 has, in a particularly advantageous manner, a concentration or
atomic fraction of sodium that is particularly low in the immediate vicinity of the surface of
10 the inner face 4 of said wall 2, advantageously between 0.0 at.% and 0.8 at.%, and even
more advantageously between 0.0 at.% and 0.5 at.%.
In comparison, the atomic fraction of sodium of the glass of a conventional borosilicate
glass container (Type I glass container) is typically equal to 6 at.% on average over all
the whole depth of the glass wall, whereas the atomic fraction of sodium of the glass of a
15 conventional soda-lime-silica glass container (Type III glass container) and of the glass
of a conventional Type II glass container (treated Type III glass container) is typically
between 6 at.% and 15 at.% on average over the whole depth of the glass wall.
As an alternative or a complement, the container 1 can advantageously have certain
particular features in terms of ratio of an atomic fraction of one or more other atomic
20 elements in the glass (in particular sodium, calcium and aluminium) to an atomic fraction
of silicon, which contribute to a particular patterning of the glass network in the vicinity of
the surface of the inner face 4, tending to still improve the glass resistance with respect
to the substance intended to be contained in the accommodation cavity 3 of the container
1.
25 In particular, the glass wall 2 of the container 1 has advantageously a ratio of an atomic
fraction of sodium to an atomic fraction of silicon, said atomic fractions being measured
by X-ray induced photoelectron spectrometry as mentioned hereinabove, that is lower
than or equal to 0.100, preferably lower than or equal to 0.090, and preferably lower than
or equal to 0.080, up to a depth of at least 300 nm (+/- 1 nm) from the surface of the inner
30 face 4.
10
As an alternative or a complement, the glass wall 2 advantageously has a ratio of an
atomic fraction of sodium to an atomic fraction of silicon, measured by X-ray induced
photoelectron spectrometry, that is lower than or equal to 0.070, preferably lower than or
equal to 0.060, and still preferably lower than or equal to 0.050, up to a depth of at least
5 200 nm (+/- 1 nm) from the surface of the inner face 4. As an alternative or a complement,
the glass wall 2 advantageously has a ratio of an atomic fraction of sodium to an atomic
fraction of silicon, measured by X-ray induced photoelectron spectrometry, that is lower
than or equal to 0.050, preferably lower than or equal to 0.040, and still preferably lower
than or equal to 0.030, up to a depth of at least 100 nm (+/- 1 nm) from the surface of the
10 inner face 4.
As an alternative or a complement, the glass wall 2 advantageously has a ratio of an
atomic fraction of sodium to an atomic fraction of silicon, measured by X-ray induced
photoelectron spectrometry, that is lower than or equal to 0.040, preferably lower than or
equal to 0.030, and still preferably lower than or equal to 0.020, up to a depth of at least
15 30 nm (+/- 1 nm) from the surface of the inner face 4. As an alternative or a complement,
the glass wall 2 advantageously has a ratio of an atomic fraction of sodium to an atomic
fraction of silicon, measured by X-ray induced photoelectron spectrometry, that is lower
than or equal to 0.030, preferably lower than or equal to 0.020, preferably lower than or
equal to 0.010, and still preferably lower than or equal to 0.005, up to a depth of at least
20 10 nm (+/- 1 nm) from the surface of the inner face 4.
The comparison between atomic fractions of sodium and silicon is here interesting in that
it reflects a comparison of an atomic concentration of modifier ion (in this case, sodium)
and an atomic concentration of former ion (in this case, silicon). The advantageous ratios
proposed hereinabove thus reflects the fact that, in the vicinity of the inner face 4 of the
25 glass wall 2, the glass is particularly rich in former ions, which contributes to its chemical
resistance.
As an alternative or a complement, the glass wall 2 advantageously has a ratio of an
atomic fraction of calcium to an atomic fraction of silicon, still measured by X-ray induced
photoelectron spectrometry, that is lower than or equal to 0.040, preferably lower than or
30 equal to 0.030, and preferably lower than or equal to 0.020, up to a depth of at least
300 nm (+/- 1 nm) from the surface of the inner face 4. As an alternative or a complement,
11
the glass wall 2 advantageously has a ratio of an atomic fraction of calcium to an atomic
fraction of silicon, measured by X-ray induced photoelectron spectrometry, that is lower
than or equal to 0.030, and preferably lower than or equal to 0.020, up to a depth of at
least 200 nm (+/- 1 nm) from the surface of the inner face 4. As an alternative or a
5 complement, the glass wall 2 advantageously has a ratio of an atomic fraction of calcium
to an atomic fraction of silicon, measured by X-ray induced photoelectron spectrometry,
that is lower than or equal to 0.010, and preferably substantially zero, up to a depth of at
least 10 nm (+/- 1 nm) from the surface of the inner face 4.
As an alternative or a complement, the glass wall 2 advantageously has a ratio of an
10 atomic fraction of aluminium to an atomic fraction of silicon, measured by X-ray induced
photoelectron spectrometry, that is lower than or equal to 0.030, and preferably lower
than or equal to 0.020, up to a depth of at least 300 nm (+/- 1 nm) from the surface of the
inner face 4. However, it is surprisingly advantageous that the glass wall 2 has an atomic
fraction of aluminium, measured by X-ray induced photoelectron spectrometry, that is
15 higher than or equal to 3 at.%, and preferably higher than or equal to 3.5 at.%, up to a
depth of at least 300 nm (+/- 1 nm) from the surface of the inner face 4. Indeed, it seems
that such an aluminium content is favourable to a densification of the glass network in the
vicinity of the inner face 4 of the glass wall 2, tending to further improve the glass
resistance with respect to the substance intended to be contained in the accommodation
20 cavity 3 of the container 1.
The migration of boron ions and/or barium ions coming from the borosilicate glass of the
container 1 to the substance intended to be contained in the latter may be a problem both
for integrity of said substance over time and from the health point of view for the final user
of said substance. Therefore, in order to provide the container 1 with excellent
25 performances in terms of control of the boron ion elution rate, the glass wall 2 has
preferably an atomic fraction of boron, measured by X-ray induced photoelectron
spectrometry, that is lower than or equal to 20.0 at.%, and preferably lower than or equal
to 15.0 at.%, up to a depth of at least 300 nm (+/- 1 nm) from the surface of the inner face
4. As an alternative or a complement, the glass wall 2 advantageously has an atomic
30 fraction of boron, measured by X-ray induced photoelectron spectrometry, that is lower
than or equal to 15.0 at.%, and preferably lower than or equal to 10.0 at.%, up to a depth
of at least 30 nm (+/- 1 nm) from the surface of the inner face 4.
12
In order to provide the container 1 with excellent performances in terms of control of the
barium ion elution rate, the glass wall 2 has preferably an atomic fraction of barium,
measured by X-ray induced photoelectron spectrometry, that is lower than or equal to 1.5
at.%, preferably lower than or equal to 1.4 at.%, preferably lower than or equal to 1.3
5 at.%, preferably lower than or equal to 1.2 at.%, preferably lower than or equal to 1.1
at.%, and preferably lower than or equal to 1.0 at.%, up to a depth of at least 300 nm
(+/- 1 nm) from the surface of the inner face 4. As an alternative or a complement, the
glass wall 2 advantageously has an atomic fraction of barium, still measured by X-ray
induced photoelectron spectrometry, that is lower than or equal to 0.9 at.%, preferably
10 lower than or equal to 0.8 at.%, still preferably lower than or equal to 0.7 at.%, up to a
depth of at least 30 nm (+/- 1 nm) from the surface of the inner face 4.
After having undergone a filling and ageing protocol as defined in chapter 660 of the USP
(U.S. Pharmacopoeia) or in chapter 3.2.1. of the European Pharmacopoeia (i.e. 1h at
121°C in an autoclave, filled with ultra-pure water), the container 1 thus has a total
15 quantity of extractables (species extracted from the glass) per surface unit that is
advantageously lower than 15x10-2 µg.cm-2
, and even more advantageously lower than
10x10-2 µg.cm-2
(for example, between 7x10-2 and 9x10-2 µg.cm-2
), among which
- a quantity of extracted sodium advantageously lower than 5x10-2 µg.cm-2
, and
even more advantageously lower than 4x10-2 µg.cm-2 (for example, between
1.5x10-2 and 3.0x10-2 µg.cm-2 20 ),
- a quantity of extracted aluminium advantageously lower than 2x10-2 µg.cm-2
, and
even more advantageously lower than 1x10-2 µg.cm-2 (for example, between
0.3x10-2 and 0.8x10-2 µg.cm-2
),
- a quantity of extracted barium advantageously lower than 1.5x10-2 µg.cm-2
, and
even more advantageously lower than 1x10-2 µg.cm-2 25 (for example, between
0.1x10-2 and 0.5x10-2 µg.cm-2
),
- a quantity of extracted zinc advantageously lower than 0.8x10-2 µg.cm-2
, and even
more advantageously lower than 0.5x10-2 µg.cm-2 (for example, between 0.0x10-2
and 0.2x10-2 µg.cm-2
).
30 Such properties in terms of quantities of extractables are inventions in their own rights.
Thus, is an invention in its own right a container 1 comprising a glass wall 2 delimiting an
accommodation cavity 3 for a substance, in particular for a pharmaceutical or diagnostic
13
substance, said glass wall 2 having an inner face 4 located facing said accommodation
cavity 3, said wall 2 being made of borosilicate glass, said inner face 4 forming a bare
glass surface intended to come into direct contact with the substance, said container 1
having a total quantity of extractables (species extracted from the glass) per surface unit
that is lower than 15x10-2 µg.cm-2
, and preferably lower than 10x10-2 µg.cm-2 5 (for
example, between 7x10-2 and 9x10-2 µg.cm-2
), after having undergone a filling and ageing
protocol as defined in chapter 660 of the USP (U.S. Pharmacopoeia) or in chapter 3.2.1.
of the European Pharmacopoeia (i.e. during 1h at 121°C in an autoclave, filled with ultrapure water).
10 Is also an invention in its own right a container 1 comprising a glass wall 2 delimiting an
accommodation cavity 3 for a substance, in particular for a pharmaceutical or diagnostic
substance, said glass wall 2 having an inner face 4 located facing said accommodation
cavity 3, said wall 2 being made of borosilicate glass, said inner face 4 forming a bare
glass surface intended to come into direct contact with the substance, said container 1
having a quantity of extracted sodium that is lower than 5x10-2 µg.cm-2 15 , and preferably
lower than 4x10-2 µg.cm-2
(for example, between 1.5x10-2 and 3.0x10-2 µg.cm-2
), after
having undergone a filling and ageing protocol as defined in chapter 660 of the USP (U.S.
Pharmacopoeia) or in chapter 3.2.1. of the European Pharmacopoeia (i.e. during 1h at
121°C in an autoclave, filled with ultra-pure water).
20 Is also an invention in its own right a container 1 comprising a glass wall 2 delimiting an
accommodation cavity 3 for a substance, in particular for a pharmaceutical or diagnostic
substance, said glass wall 2 having an inner face 4 located facing said accommodation
cavity 3, said wall 2 being made of borosilicate glass, said inner face 4 forming a bare
glass surface intended to come into direct contact with the substance, said container 1
having a quantity of extracted aluminium that is lower than 2x10-2 µg.cm-2 25 , and preferably
lower than 1x10-2 µg.cm-2
(for example, between 0.3x10-2 and 0.8x10-2 µg.cm-2
), after
having undergone a filling and ageing protocol as defined in chapter 660 of the USP (U.S.
Pharmacopoeia) or in chapter 3.2.1. of the European Pharmacopoeia (i.e. during 1h at
121°C in an autoclave, filled with ultra-pure water).
30 Is also an invention in its own right a container 1 comprising a glass wall 2 delimiting an
accommodation cavity 3 for a substance, in particular for a pharmaceutical or diagnostic
14
substance, said glass wall 2 having an inner face 4 located facing said accommodation
cavity 3, said wall 2 being made of borosilicate glass, said inner face 4 forming a bare
glass surface intended to come into direct contact with the substance, said container 1
having a quantity of extracted barium that is lower than 1.5x10-2 µg.cm-2
, and preferably
lower than 1x10-2 µg.cm-2
(for example, between 0.1x10-2 and 0.5x10-2 µg.cm-2 5 ), after
having undergone a filling and ageing protocol as defined in chapter 660 of the USP (U.S.
Pharmacopoeia) or in chapter 3.2.1. of the European Pharmacopoeia (i.e. during 1h at
121°C in an autoclave, filled with ultra-pure water).
Is also an invention in its own right a container 1 comprising a glass wall 2 delimiting an
10 accommodation cavity 3 for a substance, in particular for a pharmaceutical or diagnostic
substance, said glass wall 2 having an inner face 4 located facing said accommodation
cavity 3, said wall 2 being made of borosilicate glass, said inner face 4 forming a bare
glass surface intended to come into direct contact with the substance, said container 1
having a quantity of extracted zinc that is advantageously lower than 0.8x10-2 µg.cm-2
,
and even more advantageously lower than 0.5x10-2 µg.cm-2 15 (for example, between
0.0x10-2 and 0.2x10-2 µg.cm-2
).
Advantageously, these results may be observed by inductively coupled plasma emission
spectrometry (ICP-OES) analysis, for example using a hardware and software system
ICP-OES PerkinElmer® Optima™ 7300 DV, with a Meinhard cyclone spray chamber and
20 argon purge (white release values subtracted - acidified solutions 2% suprapure HNO3 -
without dilution. Acquisition time 20 seconds. Quantification by measuring the area under
the peak with background correction at 2 points. Systematic rinsing between samples).
In view of the above, the container 1 with a glass wall 2 according to the invention has
excellent characteristics in terms of controlling the phenomenon of elution of species
25 present in the glass, which means a particularly strong chemical resistance, and makes
said container 1 particularly suitable for receiving into its accommodation cavity 3 a
substance that is particularly sensitive to said species and/or particularly aggressive to
glass. Therefore, the container 1 according to the invention can advantageously be used
for storing
30 - certain categories of medicines that are particularly sensitive to pH changes
induced by sodium ion release by the glass,
15
- water for injection (WFI), whose storage is particularly aggressive to glass,
- certain categories of medicines that are particularly sensitive to the release of other
ions than sodium from the glass, such as aluminium, boron, barium ions, etc.
- or also, more generally, to increase the storage duration of a given substance.
5 Advantageously, but without being limited thereto, a container 1 according to the invention
can be obtained, in a manner that is particularly simple, inexpensive, efficient and safe in
terms of health and environment, from a container (or primary container) of the Type I
moulded borosilicate glass vial type, by subjecting the latter to a dealkalization treatment
of the glass in the vicinity of the surface of the inner face of its glass wall by introduction
10 into the accommodation cavity of the container, using an injection head located remote
from the opening of the container and out of the latter, whereas said glass wall is at a
temperature of about 600°C, of a liquid dose of ammonium sulphate (NH4)2SO4 dissolved
in water. Preferably, the concentration of ammonium sulphate in the liquid dose will be
chosen close or just below the saturation concentration. The volume of said liquid dose
15 may obviously vary according to the size, and in particular the nominal volume, of the
considered container.
The following, non-limiting, examples illustrate certain particularly interesting properties
of containers 1 according to the invention in terms of performance in controlling the risks
of elution of certain chemical species from the glass.
20 Example 1 – A first series of containers according to the invention has been
manufactured from primary containers of the Type I moulded borosilicate glass vial type,
of 20 mL nominal capacity. These primary containers have been subjected to a
dealkalization treatment of the glass in the vicinity of the surface of the inner face of their
glass wall by introduction into the accommodation cavity of the primary containers, using
25 an injection head located remote from the opening of the primary containers and out of
these latter, whereas the glass wall of the primary containers was at a temperature of
about 600°C, of a liquid dose of ammonium sulphate (NH4)2SO4 dissolved in water, in a
concentration close or just below the saturation concentration (volume of the liquid dose:
80 µL).
16
Table 1 below compiles results obtained for one of the containers according to Example
1, by X-ray induced photoelectron spectrometry (XPS) as described hereinabove, in
terms of atomic fraction (in at.%) and ratio of atomic fractions of certain species of the
wall glass, at different depths from the surface of the inner face of this wall.
5
Table 1
Example 2 – A second series of containers according to the invention has been
manufactured from primary containers of the Type I moulded borosilicate glass vial type,
10 of 10 mL nominal capacity. These primary containers have been subjected to a
dealkalization treatment of the glass in the vicinity of the surface of the inner face of their
glass wall by introduction into the accommodation cavity of the primary containers, using
an injection head located remote from the opening of the primary containers and out of
these latter, whereas the glass wall of the primary containers was at a temperature of
15 about 600°C, of a liquid dose of ammonium sulphate (NH4)2SO4 dissolved in water, in a
concentration close or just below the saturation concentration (volume of the liquid dose:
80 µL).
Table 2 below compiles results obtained for five containers R1 to R5 according to
Example 2, by inductively coupled plasma emission spectrometry (ICP-OES) as
20 described hereinabove, in terms of quantities of species extracted from the glass
(expressed in µg/L), after having subjected said containers to a filling and ageing protocol
as defined in chapter 660 of the USP (U.S. Pharmacopoeia) or in chapter 3.2.1. of the
European Pharmacopoeia (i.e. 1h at 121°C in an autoclave, filled with ultra-pure water).
The results obtained for containers R1 to R5 are compared with results obtained in the
25 same conditions for five containers R1' to R5' of the conventional Type I glass vial type,
of 10 mL nominal capacity. The observed quantities of extracted species are far lower in
17
the case of the containers according to the invention than the quantities of extracted
species for the known Type I glass containers.
5 Table 2
Example 3 – A third series of containers according to the invention has been
manufactured from primary containers of the Type I moulded borosilicate glass vial type,
of 20 mL nominal capacity. These primary containers have been subjected to a
dealkalization treatment of the glass in the vicinity of the surface of the inner face of their
10 glass wall by introduction into the accommodation cavity of the primary containers, using
an injection head located remote from the opening of the primary containers and out of
these latter, whereas the glass wall of the primary containers was at a temperature of
about 600°C, of a liquid dose of ammonium sulphate (NH4)2SO4 dissolved in water, in a
concentration close or just below the saturation concentration (volume of the liquid dose:
15 80 µL).
Table 3 below compiles results obtained for five containers R6 to R10 according to
Example 3, by inductively coupled plasma emission spectrometry (ICP-OES) as
described hereinabove, in terms of quantities of species extracted from the glass
(expressed in µg/L), after having subjected said containers to a filling and ageing protocol
20 as defined in chapter 660 of the USP (U.S. Pharmacopeia) or in chapter 3.2.1. of the
18
European Pharmacopeia (i.e. 1h at 121°C in an autoclave, filled with ultra-pure water).
The results obtained for containers R6 to R10 are compared with results obtained in the
same conditions for five containers R6' to R10' of the conventional Type I glass vial type,
of 20 mL nominal capacity. The observed quantities of extracted species are far lower in
5 the case of the containers according to the invention than the quantities of extracted
species for the known Type I glass containers.
Table 3
10 Example 4 – A fourth series of containers according to the invention has been
manufactured from primary containers of the Type I moulded borosilicate glass vial type,
of 50 mL nominal capacity. These primary containers have been subjected to a
dealkalization treatment of the glass in the vicinity of the surface of the inner face of their
glass wall by introduction into the accommodation cavity of the primary containers, using
15 an injection head located remote from the opening of the primary containers and out of
these latter, whereas the glass wall of the primary containers was at a temperature of
about 600°C, of a liquid dose of ammonium sulphate (NH4)2SO4 dissolved in water, in a
concentration close or just below the saturation concentration (volume of the liquid dose:
50 µL).
19
Table 4 below compiles results obtained for three containers R11 to R13 according to
Example 4, by inductively coupled plasma emission spectrometry (ICP-OES) as
described hereinabove, in terms of quantities of species extracted from the glass
(expressed in µg/L), after having subjected said containers to a filling and ageing protocol
5 as defined in chapter 660 of the USP (U.S. Pharmacopoeia) or in chapter 3.2.1. of the
European Pharmacopoeia (i.e. 1h at 121°C in an autoclave, filled with ultra-pure water).
The results obtained for containers R11 to R13 are compared with results obtained in the
same conditions for three containers R11' to R13' of the conventional Type I glass vial
type, of 50 mL nominal capacity. The observed quantities of extracted species are far
10 lower in the case of the containers according to the invention than the quantities of
extracted species for the known Type I glass containers.
Table 4
Table 5 below compiles results obtained for three other containers R14 to R16 according
15 to Example 4, in comparison with results obtained in the same conditions for three
containers R14' to R16' of the conventional Type I glass vial type, of 50 mL nominal
capacity, in terms of surface hydrolytic resistance Rh. Hydrolytic resistance Rh is here
measured in a known manner, by titration of an aliquot part of the extraction solution
(titrated volume: 100 mL) obtained with a solution of hydrochloric acid (HCL N/100), after
20 having subjected said containers to a filling and ageing protocol as defined in chapter 660
20
of the USP (U.S. Pharmacopoeia) or in chapter 3.2.1. of the European Pharmacopoeia
(i.e. 1h at 121°C in an autoclave, filled with ultra-pure water). The 90% capacity of the
containers is here of 54 mL.
5 Table 5
It is observed that the containers R14 to R16, according to the invention, have a hydrolytic
resistance Rh that is far better (i.e. far lower) than that of the known Type I glass
containers R14' to R16'. As a reminder, for such a capacity, the regulatory limit of
hydrolytic resistance Rh for a Type III glass container is of 4.8 ml HCl N/100, and that of
10 a Type II glass container is of 0.5 ml HCl N/100, for a titrated volume of 100 mL.
Example 5 – A fifth series of containers according to the invention has been
manufactured from primary containers of the Type I moulded borosilicate glass vial type,
of 100 mL nominal capacity. These primary containers have been subjected to a
dealkalization treatment of the glass in the vicinity of the surface of the inner face of their
15 glass wall by introduction into the accommodation cavity of the primary containers, using
an injection head located remote from the opening of the primary containers and out of
these latter, whereas the glass wall of the primary containers was at a temperature of
about 600°C, of a liquid dose of ammonium sulphate (NH4)2SO4 dissolved in water, in a
concentration close or just below the saturation concentration (volume of the liquid dose:
20 120 µL).
Table 6 below compiles results obtained for five containers R17 to R21 according to
Example 5, by inductively coupled plasma emission spectrometry (ICP-OES) as
described hereinabove, in terms of quantities of species extracted from the glass
(expressed in µg/L), after having subjected said containers to a filling and ageing protocol
25 as defined in chapter 660 of the USP (U.S. Pharmacopoeia) or in chapter 3.2.1. of the
European Pharmacopoeia (i.e. 1h at 121°C in an autoclave, filled with ultra-pure water).
The results obtained for containers R17 to R21 are compared with results obtained in the
21
same conditions for five containers R17' to R21' of the conventional Type I glass vial type,
of 100 mL nominal capacity. The so-observed quantities of extracted species are far lower
in the case of the containers according to the invention than the quantities of extracted
species for the known Type I glass containers.
5
Table 6
Example 6 – A sixth series of containers according to the invention has been
manufactured from primary containers of the Type I moulded borosilicate glass vial type,
10 of 50 mL nominal capacity. These primary containers have been subjected to a
dealkalization treatment of the glass in the vicinity of the surface of the inner face of their
glass wall by introduction into the accommodation cavity of the primary containers, using
an injection head located remote from the opening of the primary containers and out of
these latter, whereas the glass wall of the primary containers was at a temperature of
15 about 600°C, of a liquid dose of ammonium sulphate (NH4)2SO4 dissolved in water, in a
concentration close or just below the saturation concentration (volume of the liquid dose:
120 µL).
Table 7 below compiles results obtained for three series of three containers R22 to R30
according to Example 6, by comparison with three series of three conventional Type I
20 glass containers R22' to R30', in terms of quantities of species extracted from the glass
22
(expressed in ppb), and that for different tests described in chapter 1660 of the USP (U.S.
Pharmacopoeia):
- Test 1 (containers R22 to R24 / R24’ to R24’): measurements of species extracted
from the glass after the containers have been filled with a 0.9 % solution of
5 potassium chloride KCl at pH 8.0, then placed in an autoclave during 1 h at 121 °C;
- Test 2 (containers R25 to R27 / R25’ to R27’): measurements of species extracted
from the glass after the containers have been filled with a 3 % citric acid solution
at pH 8.0, then placed in an oven for 24 hours at 80°C;
- Test 3 (containers R28 to R30 / R28’ to R30’: measurements of species extracted
10 from the glass after the containers have been filled with a glycine solution at a
concentration of 20 mM and pH 10.0, then placed in an oven for 24 hours at 50°C.
Table 7
15 The results of the above Examples 1 to 6 thus show that the containers 1 according to
the invention have performances in terms of chemical resistance that are far higher than
those of conventional Type I containers, these latter having however intrinsically a far
better chemical resistance than Type III or Type II glass containers. The quantities of
glass species that are liable to be released by the containers 1 according to the invention
20 are particularly low, in particular as regards sodium, aluminium, boron, barium, or also
zinc. Thus, the use of containers 1 according to the invention makes it possible to store
23
and preserve particularly aggressive and/or unstable substances in excellent conditions.
It moreover generally allows extending the storage life and therefore the lifespan of
substances, and in particular pharmaceutical or diagnostic-use substances.
The invention also relates, as such, to a raw container comprising a glass wall delimiting
5 an accommodation cavity, said glass wall having an inner face located facing said
accommodation cavity. Said semi-finished, raw container is intended to form a container
1 according to the invention, as described hereinabove. Therefore, the glass wall of said
raw container prefigures that of the container 1 according to the invention. According to
the invention, said glass wall of the raw container is made of borosilicate glass, according
10 to the definition already given hereinabove, and advantageously has the same physicalchemical properties in terms of atomic fractions and ratio of atomic fractions as those,
described hereinabove, of the glass wall 2 of the container 1 according to the invention.
According to the invention, the inner face of the glass wall of the raw container forms a
glass surface that is devoid of sodium sulphate (Na2SO4) grains, which advantageously
15 constitute a residue of dealkalization treatment of the glass in the vicinity of the surface
of the inner face of the glass wall, preferably using ammonium sulphate ((NH4)2SO4). Said
raw container is thus advantageously obtained from a container with a wall made of a
typically Type I, borosilicate glass, preferably moulded glass, which has been subjected
to a dealkalization treatment to obtain the above-described physical-chemical
20 characteristics, and which has, due to this dealkalization treatment, sodium sulphate
grains at the surface of the inner face of its glass wall. Said sodium sulphate grains thus
form a powder residual deposit, which can be removed, by a suitable washing of the
surface of the inner face of the glass wall, before the accommodation cavity of the
container is finally filled with a substance, and in particular with a pharmaceutical or
25 diagnostic substance.
In accordance with the invention, said sodium sulphate grains are shaped and arranged
in a substantially uniform manner on the glass surface of the inner face, thus forming on
said surface a bloom that is white (or whitish, slightly milky in appearance), translucent
and substantially homogeneous, at least to the naked eye (i.e. from a macroscopic point
30 of view) and under illumination using light in the range visible to the human eye. Typically,
said sodium sulphate grains have a generally spherical shape. Said sodium sulphate
24
grains advantageously have an average size between 50 nm and 1,500 nm. For example,
said grains may be gathered into two populations, i.e. a population of small grains that
have an average size advantageously between 50 nm and 200 nm, and a population of
large grains that have an average size advantageously between 500 nm and 1,500 nm.
5 Said sodium sulphate grains are advantageously distributed over the glass surface of the
inner face with an average surface density from 0.2 grains / µm² to 3 grains / µm², and
preferably from 0.2 grains / µm² to 1.5 grains / µm² (grains per square micrometer). For
example, the grains may be gathered on the one hand into a population of small grains,
as mentioned hereinabove, which are distributed over the glass surface of the inner face
10 with an average surface density advantageously from 0.2 grains / µm² to 2,5 grains / µm²,
and even more advantageously from 0.5 grains / µm² to 1.5 grains / µm², and on the other
hand a population of large grains, as already mentioned hereinabove, which are
distributed over the glass surface of the inner face with an average surface density
advantageously from 0 grains / µm² to 0.5 grains / µm², and even more advantageously
15 from 0 grains / µm² to 0.1 grains / µm². These size and surface density characteristics
may be observed, for example, with a scanning electron microscope (SEM).
Formed by such sodium sulphate grains uniformly distributed over the surface of the inner
face, the white bloom is thus substantially uniform, therefore substantially free of more or
less marked, opaque spots. Preferably, the outer face of the glass wall of the raw
20 container, opposite to said inner face, forms a surface that is substantially devoid of
sodium sulphate grains (with the possible exception of a few scattered grains). However,
as an alternative, it remains conceivable that the surface of said outer face can also be
provided with sodium sulphate grains, in which case these latter are shaped and arranged
in a substantially uniform manner on the surface of the outer face, thus also forming a
25 bloom that is white (or whitish, slightly milky in appearance), translucent and substantially
homogeneous, at least to the naked eye (i.e. from a macroscopic point of view) and under
illumination using light in the range visible to the human eye.
Said raw container is intended to undergo a washing of the surface of the inner face (and,
as the case may be, of the outer face) of the glass wall in order to eliminate therefrom
30 said bloom of sodium sulphate grains, before the accommodation cavity of the soobtained container is finally filled with a substance, and in particular a pharmaceutical or
diagnostic substance. Thus, the washing of the semi-finished, raw container makes it
25
possible to eliminate the white bloom from the surface of the glass wall and to
advantageously obtain the container 1 of the invention, as described hereinabove.
Thanks to such a characteristic of homogeneity, uniformity, of the bloom formed by the
sodium sulphate grains, the glass wall of the raw container according to the invention
5 may be easily and efficiently inspected, for potential glass defect, to the naked eye or
using a conventional machine for automatic optical inspection, and that without it is
thereby necessary to proceed to any post-treatment of the glass wall (such as, in
particular, a washing, an elimination of the sulphate grains, from the surface of the glass
wall) previously to such an inspection. The quality control of the container is thus
10 particularly reliable, while being simpler and less expensive to implement. This ensures
that the container is reliably controlled, making it particularly safe.
Particularly advantageously, but without being limited thereto, a raw container according
to the invention can be obtained, in a simple and efficient manner, from a container (or
primary container) of the Type I moulded borosilicate glass vial type, by subjecting the
15 latter to a dealkalization treatment of the glass in the vicinity of the surface of the inner
face of its glass wall by introduction into the accommodation cavity of the container, using
an injection head located remote from the opening of the container and out of the latter,
whereas said glass wall is at a temperature of about 350°C, and preferably between
350°C and 800°C, of a liquid dose of ammonium sulphate (NH4)2SO4 dissolved in water.
20 Preferably, the concentration of ammonium sulphate in the liquid dose will be chosen
close or just below the saturation concentration. The volume of said liquid dose may
obviously vary according to the size, and in particular the nominal volume, of the
considered container.
It results therefrom that the containers according to the invention are not only particularly
25 effective in terms of chemical resistance, but are also particularly reliable, at a reasonable
manufacturing cost.
POSSIBILITY OF INDUSTRIAL APPLICATION
The invention finds its application in the field of glass containers, and in particular for the
packaging of pharmaceutical or diagnostic substances.
26
We Claim:
1. A container (1) comprising a glass wall (2) delimiting an accommodation cavity (3)
for a substance, in particular for a pharmaceutical or diagnostic substance, said
glass wall (2) having an inner face (4) located facing said accommodation cavity
5 (3), said container (1) being characterized in that said wall (2) is made of
borosilicate glass, said inner face (4) forming a bare glass surface intended to
come into direct contact with the substance, said glass wall (2) having an atomic
fraction of sodium, as measured by X-ray induced photoelectron spectrometry,
that is lower than or equal to 2.0 at.% up to a depth of at least 300 nm from the
10 surface of the inner face (4).
2. The container (1) according to the preceding claim, characterized in that said
atomic fraction of sodium is lower than or equal to 1.8 at.%, preferably lower than
or equal to 1.6 at.%, preferably lower than or equal to 1.4 at.%, and still preferably
lower than or equal to 1.5 at.%, up to a depth of at least 300 nm from the surface
15 of the inner face (4).
3. The container (1) according to any one of the preceding claims, characterized in
that said atomic fraction of sodium is lower than or equal to 1.6 at.%, preferably
lower than or equal to 1.4 at.%, and still preferably lower than or equal to 1.2 at.%,
up to a depth of at least 200 nm from the surface of the inner face (4).
20 4. The container (1) according to any one of the preceding claims, characterized in
that said atomic fraction of sodium is lower than or equal to 1.0 at.%, preferably
lower than or equal to 0.9 at.%, and still preferably lower than or equal to 0.8 at.%,
up to a depth of at least 100 nm from the surface of the inner face (4).
5. The container (1) according to any one of the preceding claims, characterized in
25 that said atomic fraction of sodium is lower than or equal to 0.8 at.%, and
preferably lower than or equal to 0.7 at.%, up to a depth of at least 30 nm from
the surface of the inner face (4).
27
6. The container (1) according to any one of the preceding claims, characterized in
that said atomic fraction of sodium is lower than or equal to 0.5 at.%, preferably
lower than or equal to 0.4 at.%, preferably lower than or equal to 0.3 at.%, and
still preferably lower than or equal to 0.2 at.%, up to a depth of at least 10 nm from
5 the surface of the inner face (4).
7. The container (1) according to any one of the preceding claims, characterized in
that said glass wall (2) has a ratio of an atomic fraction of sodium to an atomic
fraction of silicon, measured by X-ray induced photoelectron spectrometry, that is
lower than or equal to 0.100, preferably lower than or equal to 0.090, and
10 preferably lower than or equal to 0.080, up to a depth of at least 300 nm from the
surface of the inner face (4).
8. The container (1) according to any one of the preceding claims, characterized in
that said glass wall (2) has a ratio of an atomic fraction of sodium to an atomic
fraction of silicon, measured by X-ray induced photoelectron spectrometry, that is
15 lower than or equal to 0.070, preferably lower than or equal to 0.060, and still
preferably lower than or equal to 0.050, up to a depth of at least 200 nm from the
surface of the inner face (4).
9. The container (1) according to any one of the preceding claims, characterized in
that said glass wall (2) has a ratio of an atomic fraction of sodium to an atomic
20 fraction of silicon, measured by X-ray induced photoelectron spectrometry, that is
lower than or equal to 0.050, preferably lower than or equal to 0.040, and still
preferably lower than or equal to 0.030, up to a depth of at least 100 nm from the
surface of the inner face (4).
10.The container (1) according to any one of the preceding claims, characterized in
25 that said glass wall (2) has a ratio of an atomic fraction of sodium to an atomic
fraction of silicon, measured by X-ray induced photoelectron spectrometry, that is
lower than or equal to 0.040, preferably lower than or equal to 0.030, and still
preferably lower than or equal to 0.020, up to a depth of at least 30 nm from the
surface of the inner face (4).
28
11.The container (1) according to any one of the preceding claims, characterized in
that said glass wall (2) has a ratio of an atomic fraction of sodium to an atomic
fraction of silicon, measured by X-ray induced photoelectron spectrometry, that is
lower than or equal to 0.030, preferably lower than or equal to 0.020, preferably
5 lower than or equal to 0.010, and still preferably lower than or equal to 0.005, up
to a depth of at least 10 nm from the surface of the inner face (4).
12.The container (1) according to any one of the preceding claims, characterized in
that said glass wall (2) has a ratio of an atomic fraction of calcium to an atomic
fraction of silicon, measured by X-ray induced photoelectron spectrometry, that is
10 lower than or equal to 0.040, preferably lower than or equal to 0.030, and
preferably lower than or equal to 0.020, up to a depth of at least 300 nm from the
surface of the inner face (4).
13.The container (1) according to any one of the preceding claims, characterized in
that said glass wall (2) has a ratio of an atomic fraction of calcium to an atomic
15 fraction of silicon, measured by X-ray induced photoelectron spectrometry, that is
lower than or equal to 0.030, and preferably lower than or equal to 0.020, up to a
depth of at least 200 nm from the surface of the inner face (4).
14.The container (1) according to any one of the preceding claims, characterized in
that said glass wall (2) has a ratio of an atomic fraction of calcium to an atomic
20 fraction of silicon, measured by X-ray induced photoelectron spectrometry, that is
lower than or equal to 0.010, and preferably substantially zero, up to a depth of at
least 10 nm from the surface of the inner face (4).
15.The container (1) according to any one of the preceding claims, characterized in
that said glass wall (2) has a ratio of an atomic fraction of aluminium to an atomic
25 fraction of silicon, measured by X-ray induced photoelectron spectrometry, that is
lower than or equal to 0.030, and preferably lower than or equal to 0.020, up to a
depth of at least 300 nm from the surface of the inner face (4).
16.The container (1) according to any one of the preceding claims, characterized in
that said glass wall (2) has an atomic fraction of boron, measured by X-ray
29
induced photoelectron spectrometry, that is lower than or equal to 20.0 at.%, and
preferably lower than or equal to 15.0 at.%, up to a depth of at least 300 nm from
the surface of the inner face (4).
17.The container (1) according to any one of the preceding claims, characterized in
5 that said glass wall (2) has an atomic fraction of boron, measured by X-ray
induced photoelectron spectrometry, that is lower than or equal to 15.0 at.%, and
preferably lower than or equal to 10.0 at.%, up to a depth of at least 30 nm from
the surface of the inner face (4).
18.The container (1) according to any one of the preceding claims, characterized in
10 that said glass wall (2) has an atomic fraction of barium, measured by X-ray
induced photoelectron spectrometry, that is lower than or equal to 1.5 at.%,
preferably lower than or equal to 1.2 at.%, and preferably lower than or equal to
1.0 at.%, up to a depth of at least 300 nm from the surface of the inner face (4).
19.The container (1) according to any one of the preceding claims, characterized in
15 that said glass wall (2) has an atomic fraction of barium, measured by X-ray
induced photoelectron spectrometry, that is lower than or equal to 0.9 at.%,
preferably lower than or equal to 0.8 at.%, and still preferably lower than or equal
to 0.7 at.%, up to a depth of at least 30 nm from the surface of the inner face (4).
20.The container (1) according to any one of the preceding claims, characterized in
20 that it is made of moulded glass.
21.The container (1) according to any one of the preceding claims, characterized in
that it forms a vial or a bottle.
22.A raw container intended to form a container (1) according to any one of the
preceding claims, said raw container comprising a glass wall delimiting an
25 accommodation cavity, said glass wall having an inner face located facing said
accommodation cavity, said wall being made of borosilicate glass, said inner face
forming a glass surface provided with sodium sulphate grains shaped and
arranged in a substantially uniform manner on said surface, thus forming a
30
substantially homogeneous translucent white bloom, said raw container being
intended to undergo a washing of the surface of the glass wall inner face in order
to eliminate said bloom.
23.The raw container according to the preceding claim, wherein said sodium sulphate
5 grains have an average size between 50 nm and 1,500 nm.
24.The raw container according to any one of claims 22 and 23, wherein said sodium
sulphate grains are distributed over the glass surface of the inner face with an
average surface density from 0.2 grains / µm² to 3 grains / µm².