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 FROM SODA-LIME 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 or substance. These containers are classified according to their
15 level of 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 contain 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
20 pharmaceutical 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
25 II” glass 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
3
and the Type I glass containers, which make them suitable for packaging most of the acid
and neutral aqueous preparations.
Although particularly resistant on a chemical point of view, Type I glass containers are
generally more complicated and expensive to produce than Type II and Type III
5 containers, which substantially limits the use thereof. The chemical resistance of Type II
glass containers, although being better than that of Type III glass containers, however
remains sometimes insufficient with respect to the aggressive nature of the preparation
the container is intended to contain and/or with respect to the chemical sensitivity of this
preparation to certain species of the glass liable to migrate out of the latter during the
10 preparation storage period. That is why it is sometimes contemplated to cover the inner
face of the glass wall of the soda-lime glass containers with a barrier coating, for example
made of pure silica SiO2 or silicone-based. Nevertheless, the implementation of such a
barrier coating makes the manufacturing of the containers more complex and more
expensive.
15 DISCLOSURE OF THE INVENTION
As a result of the foregoing, the objects assigned to the present invention aim to propose
a new 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
20 moreover particularly easy to manufacture.
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
25 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 soda-lime 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, measured by X-ray induced photoelectron spectrometry, that is lower than 4 at.%
30 up to a depth of at least 200 nm from the surface of the inner face.
4
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 soda-lime
5 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.
10 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 example.
Figure 1 schematically illustrates, in vertical cross-section, a preferential embodiment of
15 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,
within the container 1. The container 1 according to the invention thus forms a primary
20 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
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
25 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
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
5
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
administered by parenteral route (general or locoregional) or to be ingested or absorbed
5 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
has a rated volume between 5 mL and 1,000 mL, which makes it particularly suitable for
10 the5aturating 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
products, etc.), veterinary, food or also cosmetic use.
15 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 soda-lime (or “soda-lime-silica”)
glass. The glass forming the wall 2 of the container 1 therefore advantageously
comprises, on average, in mass, between 71 % and 74 % of silicon oxide SiO2, between
10 % and 12 % of calcium oxide CaO, between 11 % and 14 % of sodium oxide Na2O,
20 between 0 % and 2 % of potassium oxide K2O, between 0 % and 3 % of magnesium
oxide MgO, between 0 % and 1 % of barium oxide BaO, and 1 % and 3 % of aluminium
oxide Al2O3. More advantageously, the glass of the wall 2 of the container 1 comprises,
on average, in mass, between 72 % and 74 % of silicon oxide SiO2, between 10.5 % and
11.5 % of calcium oxide CaO, between 12 % and 13 % of sodium oxide Na2O, between
25 0 % and 1.5 % of potassium oxide K2O, between 0 % and 1.5 % of magnesium oxide
MgO, between 0 % and 1 % of barium oxide BaO, and 1.5 % and 2.5 % of aluminium
oxide Al2O3. The glass of the wall 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
30 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
6
contained in the container 1 against the effects of light, in particular in certain wavelength
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).
5 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
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
10 interaction of the glass with the substance contained in the container) with respect to a
moulded glass container. Now, the 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
15 bare glass surface intended to come into direct contact with said substance. In other
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
20 is devoid of any additional barrier coating, exogenous to the glass of the wall 2, designed
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
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
25 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
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
30 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
cavity 3 against any chemical interaction between them. So formed of soda-lime glass
7
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 soda-lime glass, the wall 2 has a very
5 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
the7aturatner according to the invention has an atomic fraction of sodium that is lower
10 than 4 at.% up to a depth of at least 200 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 200 nm, the glass of the wall 2 has an atomic fraction of sodium that
does not exceed 4 at.%.
This atomic fraction, as well as all the atomic fractions which will be discussed below, is
15 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
20 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
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
25 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
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.
30 The value of atomic fraction of sodium, up to a depth of at least 200 nm (+/- 1 nm), being
thus at most equal to 4 at.%, it is even more advantageous that said atomic fraction of
8
sodium is lower than or equal to 3.5 at.%, preferably lower than or equal to 3.3 at.%,
preferably lower than or equal to 3 at.%, preferably lower than or equal to 2.8 at.%,
preferably lower than or equal to 2.6 at.%, and still preferably lower than or equal to
2.5 at.%, up to a depth of at least 200 nm (+/- 1 nm) from the surface of the inner face 4.
5 The profile of atomic fraction of sodium of the glass of the wall 2 over such a depth of
200 nm is not necessarily strictly homogeneous at any depth between 0 nm and 200 nm.
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
10 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.
Preferably, the glass wall 2 advantageously has an atomic fraction of sodium that is lower
than or equal to 3.5 at.%, preferably lower than or equal to 3.3 at.%, preferably lower than
or equal to 3 at.%, preferably lower than or equal to 2.8 at.%, preferably lower than or
15 equal to 2.6 at.%, preferably lower than or equal to 2.5 at.%, preferably lower than or
equal to 2.4 at.%, preferably lower than or equal to 2.3 at.%, and still preferably lower
than or equal to 2.2 at.%, up to a depth of at least 100 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
20 of sodium that is lower than or equal to 2.4 at.%, preferably lower than or equal to
2.3 at.%, preferably lower than or equal to 2.2 at.%, preferably lower than or equal to
2.1 at.%, preferably lower than or equal to 2.0 at.%, preferably lower than or equal to
1.9 at.%, and still preferably lower than or equal to 1.8 at.%, up to a depth of 30 nm
(+/- 1 nm) from the surface of the inner face 4.
25 As an alternative or a complement, the glass wall 2 advantageously has an atomic fraction
of sodium that is lower than or equal to 2.0 at.%, preferably lower than or equal to
1.9 at.%, preferably lower than or equal to 1.8 at.%, preferably lower than or equal to
1.7 at.%, preferably 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
30 1.3 at.%, preferably lower than or equal to 1.2 at.%, preferably lower than or equal to
9
1.1 at.%, and still preferably lower than or equal to 1.0 at.%, up to a depth of 15 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 sodium that is lower than or equal to 2.0 at.%, preferably lower than or equal to
5 1.9 at.%, preferably lower than or equal to 1.8 at.%, preferably lower than or equal to
1.7 at.%, preferably 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.%, preferably lower than or equal to 1.2 at.%, preferably lower than or equal to
1.1 at.%, and still preferably lower than or equal to 1.0 at.%, up to a depth of 7 nm from
10 the surface of the inner face 4.
As an alternative or a complement, the glass wall 2 advantageously has an atomic fraction
of sodium 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 at.%, preferably lower than or equal to
1.2 at.%, preferably lower than or equal to 1.1 at.%, preferably lower than or equal to
15 1.0 at.%, preferably lower than or equal to 0.8 at.%, preferably lower than or equal to
0.6 at.%, and still preferably lower than or equal to 0.5 at.%, at a depth of 0 nm (+/- 1 nm,
i.e. between 0 nm and 1 nm) from the surface of the inner face 4.
According to combination characterizing an especially interesting profile of atomic fraction
of sodium, the glass wall 2 advantageously has an atomic fraction of sodium that is lower
20 than or equal to 2.5 at.% up to a depth of at least 200 nm (+/- 1 nm) from the surface of
the inner face 4, lower than or equal to 2.0 at.% up to a depth of at least 30 nm (+/- 1 nm)
from the surface of the inner face 4, while being lower than or equal to 1.0 at.%, and
preferably lower than or equal to 0.5 at.%, at a depth of 0 nm (+/- 1 nm) from the surface
of the inner face 4.
25 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
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
10
to the substance intended to be contained in the accommodation cavity 3 of the container
1.
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
5 by X-ray induced photoelectron spectrometry as mentioned hereinabove, that is lower
than or equal to 0.130, preferably lower than or equal to 0.120, preferably lower than or
equal to 0.110, preferably lower than or equal to 0.100, preferably lower than or equal to
0.090, and still preferably lower than or equal to 0.080, up to a depth of at least 200 nm
(+/- 1 nm) from the surface of the inner 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 0.130, preferably lower than or
equal to 0.120, preferably lower than or equal to 0.100, preferably lower than or equal to
0.090, preferably lower than or equal to 0.080, still preferably lower than or equal to 0.070,
15 up to a depth of at least 100 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 0.080, preferably lower than or
equal to 0.070, and still preferably lower than or equal to 0.060, up to a depth of at least
20 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 0.080, preferably lower than or
equal to 0.070, preferably lower than or equal to 0.060, preferably lower than or equal to
25 0.050, and still preferably lower than or equal to 0.040, to a depth of at least 15 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 0.080, preferably lower than or
11
equal to 0.070, preferably lower than or equal to 0.060, preferably 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, to a depth of at least 7 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
5 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, preferably lower than or equal to 0.030, and still preferably lower than or
equal to 0.020, at a depth of 0 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
10 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
glass wall 2, the glass is particularly rich in former ions, which contributes to its chemical
resistance.
15 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 0.240, preferably lower than or
equal to 0.230, preferably lower than or equal to 0.220, and still preferably lower than or
equal to 0.210, up to a depth of at least 200 nm (+/- 1 nm) from the surface of the inner
20 face 4.
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, measured by X-ray induced
photoelectron spectrometry, that is lower than or equal to 0.230, preferably lower than or
equal to 0.220, and still preferably lower than or equal to 0.210, up to a depth of at least
25 100 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 calcium to an atomic fraction of silicon, measured by X-ray induced
photoelectron spectrometry, that is lower than or equal to 0.210, preferably lower than or
equal to 0.200, preferably lower than or equal to 0.190, preferably lower than or equal to
12
0.180, preferably lower than or equal to 0.170, and still preferably lower than or equal to
0.160, to a depth of at least 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 calcium to an atomic fraction of silicon, measured by X-ray induced
5 photoelectron spectrometry, that is lower than or equal to 0.200, preferably lower than or
equal to 0.180, preferably lower than or equal to 0.170, preferably lower than or equal to
0.160, preferably lower than or equal to 0.150, preferably lower than or equal to 0.140,
preferably lower than or equal to 0.130, still preferably lower than or equal to 0.120, up to
a depth of at least 15 nm (+/- 1 nm) from the surface of the inner face 4. As an alternative
10 or a 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 0.130, preferably lower than or equal to 0.120,
preferably lower than or equal to 0.110, preferably lower than or equal to 0.100, still
preferably lower than or equal to 0.090, at a depth of at least 7 nm (+/- 1 nm) from the
15 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 calcium 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, preferably lower than or equal to 0.030,
and still preferably lower than or equal to 0.020, at a depth of 0 nm (+/- 1 nm) from the
20 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 aluminium to an atomic fraction of silicon, measured by X-ray induced
photoelectron spectrometry, that is lower than or equal to 0.040, and preferably lower
than or equal to 0.030, up to a depth of at least 200 nm (+/- 1 nm) from the surface of the
25 inner face 4.
As an alternative or a complement, the glass wall 2 advantageously has a ratio of an
atomic fraction of aluminium to an atomic fraction of silicon, measured by X-ray induced
photoelectron spectrometry, that is lower than or equal to 0.040, 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
30 100 nm (+/- 1 nm) from the surface of the inner face 4.
13
As an alternative or a complement, the glass wall 2 has a ratio of an atomic fraction of
aluminium to an atomic fraction of silicon, measured by X-ray induced photoelectron
spectrometry, that is lower than or equal to 0.050, preferably 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,
5 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, the glass wall 2 has a ratio of an atomic fraction of aluminium
to an atomic fraction of silicon, measured by X-ray induced photoelectron spectrometry,
that is lower than or equal to 0.050, preferably 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
10 depth of at least 15 nm (+/- 1 nm) from the surface of the inner face 4.
As an alternative or a complement, the glass wall 2 has a ratio of an atomic fraction of
aluminium to an atomic fraction of silicon, measured by X-ray induced photoelectron
spectrometry, that is lower than or equal to 0.040, preferably lower than or equal to 0.030,
and still preferably lower than or equal to 0.020, at a depth of 0 nm (+/- 1 nm) from the
15 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
quantity of extractables (species extracted from the glass) per surface unit that is
advantageously lower than 1.50x10-1 µg.cm-2 20 , and even more advantageously lower than
1.00x10-1 µg.cm-2
, among which a quantity of extracted sodium advantageously lower
than 0.80x10-1 µg.cm-2
, and even more advantageously lower than 0.50x10-1 µg.cm-2
.
After having undergone a filling protocol as defined in chapter 660 of the USP (U.S.
Pharmacopoeia) or in chapter 3.2.1. of the European Pharmacopoeia, and having
25 undergone an ageing in an autoclave for 6h in continuous at 121°C, filled with ultra-pure
water, the container 1 according to the invention thus has a total quantity of extractables
per surface unit that is advantageously lower than 8.0x10-1 µg.cm-2
, and even more
advantageously lower than 2.5x10-1 µg.cm-2
, among which a quantity of extracted sodium
advantageously lower than 2.50x10-1 µg.cm-2
, and even more advantageously lower than
1.50x10-1 µg.cm-2 30 .
14
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
argon purge (white release values subtracted – acidified solutions 2% suprapure HNO3
5 – without dilution. Acquisition time 20 seconds. Quantification by measuring the area
under the peak with background correction at 2 points. Systematic rinsing between
samples).
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
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 soda-lime 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 1.50x10-1 µg.cm-2
, and still preferably lower than 1.00x10-1 µg.cm-2 15 , 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
20 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 soda-lime 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 0.80x10-1 µg.cm-2
, and preferably lower
than 0.50x10-1 µg.cm-2 25 , 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 moreover 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
30 diagnostic substance, said glass wall 2 having an inner face 4 located facing said
accommodation cavity 3, said wall 2 being made of soda-lime glass, said inner face 4
15
forming a bare glass surface intended to come into direct contact with the substance, said
container 1 having a total quantity of extractables per surface unit that is lower than
8.0x10-1 µg.cm-2
, and preferably lower than 2.5x10-1 µg.cm-2
, after having undergone a
filling protocol as defined in chapter 660 of the USP (U.S. Pharmacopoeia) or in chapter
5 3.2.1. of the European Pharmacopoeia, and having undergone an ageing in an autoclave
for 6h in continuous at 121°C, filled with ultra-pure water.
Is further 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
10 accommodation cavity 3, said wall 2 being made of soda-lime 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 sodium extracted that is lower than 2.50x10-1 µg.cm-2
,
and preferably lower than 1.50x10-1 µg.cm-2
, after having undergone a filling protocol as
defined in chapter 660 of the USP (U.S. Pharmacopoeia) or in chapter 3.2.1. of the
15 European Pharmacopoeia, and having undergone an ageing in an autoclave for 6h in
continuous at 121°C, filled with ultra-pure water.
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
present in the glass, which means a particularly strong chemical resistance, and makes
20 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.
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
25 terms of health and environment, from a container (or primary container) of the Type III
moulded soda-lime 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
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
30 temperature between about 500°C and 600°C, of a liquid dose of ammonium sulphate
(NH4)2SO4 dissolved in water. Preferably, the concentration of ammonium sulphate in the
16
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.
The following, non-limiting, examples illustrate certain particularly interesting properties
5 of containers 1 according to the invention in terms of performance in controlling the risks
of elution of certain chemical species from the glass.
Example 1 – A first series of containers 1 according to the invention has been
manufactured from primary containers of the Type III moulded soda-lime glass vial type,
of 20 mL nominal capacity. These primary containers have been subjected to a
10 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
about 600°C, of a liquid dose of ammonium sulphate (NH4)2SO4 dissolved in
15 demineralized water, in a concentration close or just below the saturation concentration
(volume of the liquid dose: 26 µL).
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
20 wall glass, at different depths from the surface of the inner face of this wall.
Table 1
C1s Al2p Mg2s Si2p K2p Ca2p O1s Na1s Na/Si Ca/Si Al/Si
0 6.9 0.8 0.3 30.7 0.4 0.3 60.1 0.5 0.016 0.01 0.026
6.9 0 1.2 0.5 31.9 0.5 3.3 60.9 1.6 0.05 0.103 0.038
14.9 0 0.9 0.8 29.8 0.3 5.4 61 1.7 0.057 0.181 0.03
29.9 0 0.5 0.6 29.9 0.3 6.1 60.9 1.6 0.054 0.204 0.017
99.6 0 0.8 0.5 29.8 0.3 6.2 60.4 2 0.067 0.208 0.027
199.2 0 0.9 0.6 29.3 0.3 6.6 60.1 2.2 0.075 0.225 0.031
Atomic fractions of elementary species (at.%) Atomic fraction ratios Depth (nm)
Example 1
17
Table 2 below compiles results obtained for five containers R1 to R5 according to
Example 1, 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).
Table 2
Table 3 below compiles results obtained for five containers R6 to R10 according to
10 Example 1, 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 protocol as defined
in chapter 660 of the USP (U.S. Pharmacopoeia) or in chapter 3.2.1. of the European
Pharmacopoeia, and an ageing in an autoclave for 6h in continuous at 121°C, filled with
15 ultra-pure water.
Elementary
species
R1 R2 R3 R4 R5 Average
Si 66 64 70 66 70 67
N a 108 113 111 115 123 114
K 8 9 10 11 10 10
C a 21 8 10 9 9 11
Mg 6 7 2 3 2 4
Al 2 2 2 3 2 2
Fe 3 10 18 0 0 6
B 0 0 0 0 0 0
Ba 0 0 0 0 0 0
Ti 0 0 0 0 0 0
Zn 0 0 0 0 0 0
Total extractables 215 214 224 206 216 215
Example 1
(quantities in µg/L)
18
Table 3
Example 2 – A second series of containers 1 according to the invention has been
manufactured from primary containers of the Type III moulded soda-lime glass vial type,
5 of 30 mL nominal capacity. These primary containers have been subjected to a
dealkalization treatment identical to that of Example 1, but with a liquid dose volume of
28 µL.
Table 4 below compiles results obtained for one of the containers according to Example
2, by X-ray induced photoelectron spectrometry (XPS) as described hereinabove, in
10 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.
Table 4
Elementary
species
R6 R7 R8 R9 R10 Average
Si 451 704 727 492 623 599
N a 273 332 330 309 303 309
K 31 40 44 33 34 36
C a 58 68 91 81 78 75
Mg 9 14 17 8 13 12
Al 15 23 25 15 21 20
Fe 1 1 1 1 0 1
B 0 0 0 0 0 0
Ba 1 1 1 1 1 1
Ti 0 1 1 0 1 1
Zn 2 1 2 3 2 2
Total extractables 840 1,184 1,237 942 1,075 1,056
Example 1
(quantities in µg/L)
C1s Al2p Mg2s Si2p K2p Ca2p O1s Na1s Na/Si Ca/Si Al/Si
0 7.3 0.7 0.2 30.0 0.7 1.1 59.1 1.0 0.033 0.037 0.023
6.9 0.0 1.4 0.7 31.2 0.5 3.6 60.8 1.7 0.054 0.115 0.045
14.9 0.0 1.1 1.0 30.3 0.3 5.8 59.9 1.6 0.053 0.191 0.036
29.9 0.0 1.3 0.8 29.2 0.4 5.9 60.7 1.7 0.058 0.202 0.045
99.6 0.0 0.8 0.7 29.6 0.4 6.3 60.2 2.1 0.071 0.213 0.027
199.2 0.0 0.9 0.6 29.6 0.3 6.0 60.5 2.3 0.078 0.203 0.030
Atomic fractions of elementary species (at.%) Atomic fraction ratios Depth (nm)
Example 2
19
Table 5 below compiles results obtained for five containers R11 to R15 according to
Example 2, 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).
Table 5
Table 6 below compiles results obtained for four containers R16 to R19 according to
10 Example 2, 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 protocol as defined
in chapter 660 of the USP (U.S. Pharmacopoeia) or in chapter 3.2.1. of the European
Pharmacopoeia, and an ageing in an autoclave for 6h in continuous at 121°C, filled with
15 ultra-pure water.
20
Table 6
Example 3 – A third series of containers 1 according to the invention has been
manufactured from primary containers of the Type III moulded soda-lime glass vial type,
5 of 50 mL nominal capacity. These primary containers have been subjected to a
dealkalization treatment identical to that of Example 1, but with a liquid dose volume of
26 µL.
Table 7 below compiles results obtained for one of the containers according to Example
3, by X-ray induced photoelectron spectrometry (XPS) as described hereinabove, in
10 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.
Table 7
Elementary
species
R16 R17 R18 R19 Average
Si 1,117 641 1,093 718 892
Na 423 396 400 338 389
K 56 37 62 43 49
Ca 131 57 130 72 97
Mg 26 12 26 17 20
Al 41 23 42 29 34
Fe 1 1 1 1 1
B 0 0 0 0 0
Ba 1 0 1 1 1
Ti 1 0 1 1 1
Zn 0 0 0 0 0
Total extractables 1,796 1,167 1,755 1,218 1,484
Example 2
(quantities in µg/L)
C1s Al2p Mg2s Si2p K2p Ca2p O1s Na1s Na/Si Ca/Si Al/Si
0 6.7 0.7 0.0 29.6 0.6 0.6 61.3 0.6 0.020 0.020 0.024
6.9 0.0 1.0 0.6 30.9 0.5 3.4 62.1 1.6 0.052 0.110 0.032
14.9 0.0 1.0 0.8 29.7 0.3 5.5 61.0 1.7 0.057 0.185 0.034
29.9 0.0 0.9 0.7 29.3 0.5 6.0 60.9 1.8 0.061 0.205 0.031
99.6 0.0 1.1 0.7 29.5 0.2 6.1 60.3 2.2 0.075 0.207 0.037
199.2 0.0 0.7 0.9 28.9 0.3 5.9 60.7 2.6 0.090 0.204 0.024
Depth (nm) Atomic fractions of elementary species (at.%) Atomic fraction ratios
Example 3
21
Table 8 below compiles results obtained for five containers R20 to R24 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
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).
Table 8
Table 9 below compiles results obtained for five containers R25 to R29 according to
10 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 protocol as defined
in chapter 660 of the USP (U.S. Pharmacopoeia) or in chapter 3.2.1. of the European
Pharmacopoeia, and an ageing in an autoclave for 6h in continuous at 121°C, filled with
15 ultra-pure water.
Elementary
species
R20 R21 R22 R23 R24 Average
Si 54 54 39 48 82 55
N a 117 114 60 97 132 104
K 22 23 11 15 26 20
C a 121 38 8 10 32 42
Mg 14 7 3 2 3 6
Al 4 27 0 2 3 7
Fe 1 10 0 0 0 2
B 0 16 0 0 1 3
Ba 1 1 1 0 0 1
Ti 0 0 0 0 0 0
Zn 22 5 1 1 3 6
Total extractables 357 296 122 175 283 247
Example 3
(quantities in µg/L)
22
Table 9
Example 4 – A fourth series of containers 1 according to the invention has been
manufactured from primary containers of the Type III moulded soda-lime glass vial type,
5 of 100 mL nominal capacity. These primary containers have been subjected to a
dealkalization treatment identical to that of Example 1, but with a liquid dose volume of
30 µL.
Table 10 below compiles results obtained for one of the containers according to Example
4, by X-ray induced photoelectron spectrometry (XPS) as described hereinabove, in
10 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.
Table 10
Elementary
species
R25 R26 R27 R28 R29 Average
Si 262 157 234 232 223 222
N a 274 128 201 233 228 213
K 44 36 39 39 40 39
C a 54 44 34 40 42 43
Mg 9 9 7 6 6 7
Al 11 7 10 10 10 10
Fe 0 0 0 7 0 1
B 0 0 0 0 0 0
Ba 0 0 0 0 0 0
Ti 0 0 0 0 0 0
Zn 1 0 0 0 0 0
Total extractables 655 381 525 568 550 535
Example 3
(quantities in µg/L)
C1s Al2p Mg2s Si2p K2p Ca2p O1s Na1s Na/Si Ca/Si Al/Si
0 5.1 0.7 0.5 30.4 0.6 1.2 61.0 0.6 0.020 0.039 0.023
6.9 0.0 0.9 0.7 30.7 0.4 4.2 62.0 1.0 0.033 0.137 0.029
14.9 0.0 1.1 0.7 30.4 0.3 5.8 60.8 1.0 0.033 0.191 0.036
29.9 0.0 0.7 0.7 29.8 0.3 6.0 61.3 1.3 0.044 0.201 0.023
99.6 0.0 0.9 0.7 29.7 0.5 6.1 60.2 1.9 0.064 0.205 0.030
199.2 0.0 0.8 0.8 29.4 0.2 6.0 60.3 2.5 0.085 0.204 0.027
Depth (nm) Atomic fractions of elementary species (at.%) Atomic fraction ratios
Example 4
23
Table 11 below compiles results obtained for five containers R30 to R34 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).
Table 11
Table 12 below compiles results obtained for five containers R35 to R39 according to
10 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 protocol as defined
in chapter 660 of the USP (U.S. Pharmacopoeia) or in chapter 3.2.1. of the European
Pharmacopoeia, and an ageing in an autoclave for 6h in continuous at 121°C, filled with
15 ultra-pure water.
24
Table 12
Example 5 – A fifth series of containers 1 according to the invention has been
manufactured from primary containers of the Type III moulded soda-lime glass vial type,
5 of 250 mL nominal capacity. These primary containers have been subjected to a
dealkalization treatment identical to that of Example 1, but with a liquid dose volume of
42 µL.
Table 13 below compiles results obtained for one of the containers according to Example
5, by X-ray induced photoelectron spectrometry (XPS) as described hereinabove, in
10 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.
Table 13
25
Table 14 below compiles results obtained for five containers R40 to R44 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
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).
Table 14
Table 15 below compiles results obtained for five containers R45 to R49 according to
10 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 protocol as defined
in chapter 660 of the USP (U.S. Pharmacopoeia) or in chapter 3.2.1. of the European
Pharmacopoeia, and an ageing in an autoclave for 6h in continuous at 121°C, filled with
15 ultra-pure water.
26
Table 15
The results of Examples 1 to 5 hereinabove illustrate that containers according to the
invention have quantities of elementary species released by the glass that are particularly
5 small, in particular as regards silicon, sodium, aluminium, boron, barium and zinc. This
indicates an excellent chemical resistance of the glass of the containers, and guarantees
a storage duration of substances within these latter in optimum conditions.
The26aturation also relates, as such, to a raw 26aturatner comprising a glass wall
delimiting an accommodation cavity, said glass wall having an inner face located facing
10 said accommodation cavity. Said semi-finished, raw container is intended to form a
container 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 soda-lime glass,
according to the definition already given hereinabove, and advantageously has the same
15 physical-chemical properties in terms of atomic fractions and ratio of atomic fractions as
those, described hereinabove, of the glass wall 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
20 constitute a residue of dealkalization treatment of the glass in the vicinity of the surface
27
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 III, soda-lime glass, preferably moulded glass, which has been subjected
to a dealkalization treatment to obtain the above-described physical-chemical
5 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
10 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
15 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
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
20 large grains that have an average size advantageously between 500 nm and 1,500 nm.
Said sodium sulphate grains are advantageously distributed over the glass surface of the
inner face with an average surface density from 0.1 grains / µm² to 30 grains / µm², and
preferably from 0.1 grains / µm² to 25 grains / µm² (grains per square micrometer). For
example, the grains may be gathered on the one hand into a population of small grains,
25 as mentioned hereinabove, which are distributed over the glass surface of the inner face
with an average surface density advantageously from 3 grains / µm² to 25 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 0.13 grains / µm² to 4 grains / µm². These size and surface
30 density characteristics may be observed, for example, with a scanning electron
microscope (SEM).
28
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
container, opposite to said inner face, forms a surface that is substantially devoid of
5 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
bloom that is white (or whitish, slightly milky in appearance), translucent and substantially
10 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
said bloom of sodium sulphate grains, before the accommodation cavity of the so15 obtained 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
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
20 sodium sulphate grains, the glass wall of the raw container according to the invention
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
25 wall) previously to such an inspection. The quality control of the container is thus
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
30 primary container) of the Type III moulded soda-lime glass vial type, by subjecting the
latter to a dealkalization treatment of the glass in the vicinity of the surface of the inner
29
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, still preferably between 350°C and 700°C, of a liquid dose of
5 ammonium sulphate (NH4)2SO4 dissolved in ultra-pure water. Preferably, the
concentration of ammonium sulphate in the liquid dose will be chosen close or just below
the29aturationn 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
10 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.
15
30
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 sodalime glass, said inner face (4) forming a bare glass surface intended to come into
direct contact with said substance, said glass wall (2) having an atomic fraction of
sodium, as measured by X-ray induced photoelectron spectrometry, that is lower
than 4 at.% up to a depth of at least 200 nm from the surface of the inner face (4).
10 2. The container (1) according to the preceding claim, characterized in that said
atomic fraction of sodium is lower than or equal to 3.5 at.%, preferably lower than
or equal to 3 at.%, and still preferably lower than or equal to 2.5 at.%, up to a
depth of at least 200 nm from the surface of the inner face (4).
3. The container (1) according to any one of the preceding claims, characterized in
15 that said atomic fraction of sodium is lower than or equal to 3.5 at.%, preferably
lower than or equal to 3 at.%, and still preferably lower than or equal to 2.2 at.%,
up to a depth of at least 100 nm from the surface of the inner face (4).
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 2.4 at.%, preferably
20 lower than or equal to 2.2 at.%, preferably lower than or equal to 2.0 at.%, and
still preferably lower than or equal to 1.8 at.%, up to a depth of 30 nm from the
surface of the inner face (4).
5. 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 2.0 at.%, preferably
25 lower than or equal to 1.6 at.%, preferably lower than or equal to 1.2 at.%, and
still preferably lower than or equal to 1.0 at.%, up to a depth of 15 nm from the
surface of the inner face (4).
31
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 1.5 at.%, preferably
lower than or equal to 1.2 at.%, preferably lower than or equal to 0.6 at.%, and
still preferably lower than or equal to 0.5 at.%, at a depth of 0 nm from the surface
5 of the inner face (4).
7. 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 2.5 at.% up to a depth
of at least 200 nm from the surface of the inner face (4), lower than or equal to
2.0 at.% up to a depth of at least 30 nm from the surface of the inner face (4),
10 while being lower than or equal to 1.0 at.%, and preferably lower than or equal to
0.5 at.%, at a depth of 0 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 0.130, preferably lower than or equal to 0.100, preferably
lower than or equal to 0.090, and still preferably lower than or equal to 0.080, 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 0.130, preferably lower than or equal to 0.100, preferably
lower than or equal to 0.080, still preferably lower than or equal to 0.070, 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 0.080, preferably lower than or equal to 0.070, and still
preferably lower than or equal to 0.060, up to a depth of at least 30 nm from the
surface of the inner face (4).
32
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 0.080, preferably lower than or equal to 0.070, preferably
5 lower than or equal to 0.060, and still preferably lower than or equal to 0.040, up
to a depth of at least 15 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 sodium to an atomic
fraction of silicon, measured by X-ray induced photoelectron spectrometry, that is
10 lower than or equal to 0.050, preferably 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 at a
depth of 0 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 0.240, preferably lower than or equal to 0.230, preferably
lower than or equal to 0.220, and still preferably lower than or equal to 0.210, 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
20 that said glass wall 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 0.230, preferably lower than or equal to 0.220, and still preferably
lower than or equal to 0.210, up to a depth of at least 100 nm from the surface of
the inner face (4).
25 15.The container (1) according to any one of the preceding claims, characterized in
that said glass wall 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 0.210, preferably lower than or equal to 0.180, preferably lower
than or equal to 0.170, and still preferably lower than or equal to 0.160, up to a
30 depth of at least 30 nm from the surface of the inner face (4).
33
16.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
lower than or equal to 0.200, preferably lower than or equal to 0.180, preferably
5 lower than or equal to 0.160, still preferably lower than or equal to 0.120, up to a
depth of at least 15 nm from the surface of the inner face (4).
17.The container (1) according to any one of the preceding claims, characterized in
that said glass wall 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
10 than or equal to 0.050, preferably lower than or equal to 0.040, preferably lower
than or equal to 0.030, still preferably lower than or equal to 0.020, at a depth of
0 nm from the surface of the inner face (4).
18.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
15 fraction of silicon, measured by X-ray induced photoelectron spectrometry, that is
lower than or equal to 0.040, and still preferably lower than or equal to 0.030, up
to a depth of at least 200 nm from the surface of the inner face (4).
19.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
20 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 100 nm from the
surface of the inner face (4).
20.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 aluminium 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, 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).
34
21.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
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, preferably
5 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 nm from the surface of the inner face (4).
22.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
fraction of silicon, measured by X-ray induced photoelectron spectrometry, that is
10 lower than or equal to 0.040, and preferably lower than or equal to 0.030, at a
depth of 0 nm from the surface of the inner face (4).
23.The container (1) according to any one of the preceding claims, characterized in
that it forms a vial or a bottle.
24.The container (1) according to any one of the preceding claims, characterized in
15 that it is made of moulded glass.
25.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
accommodation cavity, said glass wall having an inner face located facing said
accommodation cavity, said wall being made of soda-lime glass, said inner face
20 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.
25 26.The raw container according to the preceding claim, wherein said sodium sulphate
grains have an average size between 50 nm and 1,500 nm.
35
27.The raw container according to any one of claims 25 and 26, wherein said sodium
sulphate grains are distributed over the glass surface of the inner face with an
average surface density from 0.1 grains / µm² to 30 grains / µm².