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behaviour can be adapted to the requirements of the respective production and
processing process by replacement of thes
e oxides by one another. In addition,
CaO improves the acid resistance. CaO and MgO decrease the processing
temperature and are, if present, firmly bound into the glass structure. The sum
CaO + SrO + MgO should preferably not exceed 2.5% by weight since otherwise
the release of alkali would increase.
The glass can contain 0 – 0.5% by weight of ZrO
2
. ZrO
2
improves the hydrolytic
resistance and especially the alkali resistance of the glass. At higher proportions,
the processing temperature would be increased too greatly and the good
fusibility would be lost. The glass particularly preferably does not contain any
ZrO
2
apart from unavoidable or difficult-to-avoid impurities.
The glass can contain 0 – 0.5% by weight of TiO
2
. When used to replace SiO
2
,
TiO
2
reduces the processing temperature. At higher proportions, a brownish
discoloration of the glass would occur. The glass particularly preferably does not
contain any TiO
2
apart from unavoidable or difficult-to-avoid impurities.
The glass can contain 0 – 1% by weight of CeO
2
. In low concentrations, CeO
2
acts as refining agent, and in higher concentrations it prevents discoloration of
the glass by radioactive radiation. Primary packaging which has been produced
using such a CeO
2
-containing glass and filled can therefore be inspected visually
for any particles present even after being subjected to radioactivity. Higher CeO
2
concentrations make the glass more expensive and lead to an undesirable
yellow-brownish intrinsic coloration. For applications in which the ability to avoid
discoloration due to radioactive radiation is not important, preference is given to
a CeO
2
content in the range from 0 to 0.3% by weight.
Furthermore, the glass can contain 0 – 0.6% by weight of F
-
. This reduces the
viscosity of the melt, which accelerates melting of the mix and refining of the
melt. In addition, buffering of the pH of an aqueous solution in contact with the
7
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glass is achieved with increasing F content. That is to say, the rise in the pH in
the fill material generated by the release of alkali from the inner glass surface
after packaging of materials for inject
ion in glass containers is partially
neutralized by F ions.
The glass can be refined using, apart from the abovementioned fluorides, for
example CaF
2
,
conventional refining agents such as chlorides, for example NaCl,
and/or sulfates, for example Na
2
SO
4
or BaSO
4
, or else using CeO
2
, which are
present in customary amounts, i.e. in amounts of from 0.001 to 1% by weight,
depending on the amount and type of refining agent used, in the finished glass.
When As
2
O
3
and Sb
2
O
3
are not used, the glasses are As
2
O
3
- and Sb
2
O
3
-free
except for unavoidable impurities, which is particularly advantageous for use
thereof as pharmaceutical primary packaging.
The barium-free borosilicate glass of the invention thus contains (in % by weight
on an oxide basis)
SiO
2
71.0 – 74.5
B
2
O
3
8.0 – 9.5
Al
2
O
3
4.6 – 6.0
Na
2
O 7.0 – 8.4
K
2
O 1.7 – 2.7
Li
2
O 0 – 0.3
MgO 0 – 0.3
CaO 0.8 – 1.6
SrO 0.4 – 1.2
TiO
2
0 – 0.5
ZrO
2
0 – 0.5
F
-
0 – 0.6
CeO
2
0 – 1.0
8
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and also conventional refining agents in customary amounts.
Preference is given to the glass consisting essentially of the components
mentioned in the proportions mentioned; particular preference is given to the
glass consisting of the components mentioned in the proportions mentioned.
The barium-free borosilicate glass of the invention preferably contains (in % by
weight on an oxide basis)
SiO
2
72.0 – 73.5
B
2
O
3
8.3
–
9.5
Al
2
O
3
5.0
–
6.0
Na
2
O 7.3
–
8.2
K
2
O 2.0
–
2.5
MgO
0 – 0.3
CaO 1.0
–
1.5
SrO 0.5
–
1.0
CeO
2
0 – 0.3
F
-
0 – 0.5
and optionally conventional refining agents in customary amounts.
Preference is given to the glass consisting essentially of the components
mentioned in the proportions mentioned; particular preference is given to the
glass consisting of the components mentioned in the proportions mentioned.
Two examples of a glass (A) according to the invention and five comparative
examples (V) were melted from conventional raw materials.
Table 1 reports the respective composition (in % by weight on an oxide basis),
the coefficient of thermal expansion

(20°C; 300°C)

10
-6
/K

, the glass transition
9
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temperature T
g

C

, the processing temperature V
A

C

, the density
ρ
[g/cm
3
]
and the hydrolytic resistance of the glasses.
The hydrolytic resistance was determined as follows:

The hydrolytic resistance HGB in accordance with ISO 719. The figure
reported is in each case the base equivalent of the acid consumption in

g of
Na
2
Oeq/g of glass grains. The maximum value for a chemically highly
resistant glass of hydrolytic class 1 is 31

g of Na
2
Oeq/g of glass.

The hydrolytic resistance HGA in accordance with ISO 720 or USP. The figure
reported is in each case the acid consumption per g of glass grains. The
maximum value for a chemically highly re
sistant glass of hydrolytic class 1 is
0.1 ml/g of glass.
In the case of the hydrolytic resistance HGB which is particularly important for
pharmaceutical purposes, the glasses having base equivalents of

19 μg of
Na
2
O/g, which do not belong to class 1 but represent low values even within
HGB = 1, give very good results.
The glasses of the invention are therefore outstandingly suitable for all
applications in which chemically resistant glasses are required, e.g. for laboratory
applications, for chemical plants, for example as tubes, and in particular as
containers for medical purposes, for pharmaceutical primary packaging such as
ampoules, bottles, syringes or cartridges.
Furthermore, it has been found that the glasses of the invention display good
chemical resistance in contact with liquid contents, e.g. solutions of active
compounds, solvents, e.g. buffer systems, or the like which are present in the pH
range from 1 to 11, more preferably in the pH range from 4 to 9, very particularly
preferably in the pH range from 5 to 7, and are therefore particularly well suited
for storage or keeping in stock of these contents.
10
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26
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The g
lasses of the invention are thus outstandingly suitable for producing
pharmaceutical containers which are in contact with contents and can therefore
be provided for accommodation and storage thereof. Contents which can be
used are, for example, all solid and liquid compositions used in the
pharmaceutical sector.
Contents which may be mentioned by way of example, without implying a
restriction to these: a liquid medicament preparation, a solution comprising one
or more active compounds and optionally of auxiliary and additives, buffer
systems of all types, e.g. so
dium bicarbonate
buffers such as
a 1 molar sodium
bicarbonate solution (NaHCO
3
) 8.4% having a pH in the range from 7.0 to 8.5;
citrate buffers such as 10 mmol citrate buffer pH = 6 with 150 mmol of NaCl and
0.005% of Tween 20; phosphate buffers such as 10 mmol phosphate buffer
pH = 7.0 with 150 mmol of NaCl and 0.005% of Tween 20, or water for injection
purposes, e.g. Sartorius high-purity water, flushed through a 0.2 μm filter and
having a specific re
sistance of 18.2 M
Ω

cm (corresponds to a conductivity of
0.055
μ
S/cm). Further possible contents will be readily apparent to a person
skilled in the art.
The invention also provides for the use of the borosilicate glasses of the
invention as pharmaceutical primary packaging for accommodating and storing
liquid contents which have a pH in the range from 1 to 11, more preferably in the
range from 4 to 9, very particularly preferably in the range from 5 to 7, where the
liquid contents are preferably selected from among solutions of active
compounds, buffer solutions or water for injection purposes. The invention also
provides such pharmaceutical primary packaging.
The invention also provides a pharmaceutical combination comprising the
pharmaceutical primary packaging which co
ntains a liquid content having a pH in
the range from 1 to 11, more preferably in the range from 4 to 9, very particularly
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preferably in the range from 5 to 7, where the liquid content is preferably
selected from among a solution of an active compound, buffer solution or water
for injection purposes.
The very low processing temperatures V
A
of not more than 1120

C characterize
the good processability of the glasses. The melting temperatures of the glasses
are very low. They are about 1560°C. The favourable melting and processing
range brought about thereby reduces the energy consumption in the production
process.
The glasses are free of BaO and in a preferred embodiment free of As
2
O
3
and
Sb
2
O
3
, which is particularly advantageous for use as pharmaceutical primary
packaging. Even without the presence of BaO, a sufficiently low processing
temperature is achieved without the hydrolytic resistance being impaired.
The glasses have a glass transition temperature T
g
of about 560°C.
It is in the normal range for pharmaceutical glasses.
The glasses have a coefficient of thermal expansion

(20°C; 300°C) in the range
from 5.8

10
-6
/K to 6.2

10
-6
/K.
In terms of their linear expansion, they are therefore in the same range as the
barium-containing glasses which they are to replace.
The glasses also have a crystallization st
ability which is satisfactory for tube
drawing.
12
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26
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Table 1:
Compositions (in % by weight on an oxide basis) of the working examples (A1,
A2) and the comparative examples (V1 – V5) and the significant properties
thereof:
A1 A2 V1 V2 V3 V4 V5
SiO
2
72.8 73.4 72.2 73.5 74.85 74.85 72.0
B
2
O
3
9.0 9.0 9.1 8.6 8.95 9.0 8.75
Al
2
O
3
5.5 5.5 5.9 5.0 4.8 4.8 4.7
Na
2
O
7.9 7.7 7.9 7.9 8.2 7.6 6.3
K
2
O
2.3 2.1 2.3 1.8 1.9 2.45 2.8
MgO
- - - - 0.3 0.2 0.2
CaO
SrO
1.4
0.8
1.2
0.8
1.9
0.4
0.7
2.5
0.7
-
0.8
-
1.1
-
BaO
- - - - - - 3.75
F
-
0.3 0.3 0.3 - 0.3 0.3 0.4

(20°C;300°C)

10
-6
/K

6.08 5.96 6.09 6.01 6.08 6.08 6.05
T
g

C

558 555 546 566 557 557 557
V
A

C

ρ
[g/cm
3
]
USP/ISO720
titrated
HGA class
1100
2.38
0.058
1
1118
2.38
0.050
1
1104
n.d.
0.067
1
1113
n.d.
0.072
1
1120
2.38
0.056
1
1120
n.d.
0.056
1
1105
2.45
0.058
1
HGB

g of
Na
2
O/g glass

17 15 20 22 16 16 17
n.d. = not determined
13
P 4626
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The working examples clearly show that despite being free of BaO the glasses of
the invention combine a very low processing temperature and a very good
hydrolytic resistance, two properties which have hitherto not been able to be
combined with one another in the known BaO-free glasses having the desired
expansion. They are comparable in terms of their properties and therefore
compatible in production with the BaO-containing comparative example V5, but
with the advantage of freedom from BaO and therefore particular suitability for
pharmaceutical primary packaging. The two working examples demonstrate the
relationship between release of alkali and processing temperature. Thus,
depending on requirements and within the boundaries of the present invention,
either the processing temperature or the release of alkali can be lowered, in each
case at the justifiable expense of the other parameter.

Claims:Claims

1. Barium-free borosilicate glass which contains (in % by weight on an oxide basis)

SiO2 71.0 – 74.5
B2O3 8.0 – 9.5
Al2O3 4.6 – 6.0
Na2O 7.0 – 8.4
K2O 1.7 – 2.7
Li2O 0 – 0.3
MgO 0 – 0.3
CaO 0.8 – 1.6
SrO
TiO2
ZrO2 0.4 – 1.2
0 – 0.5
0 – 0.5
CeO2 0 – 1.0
F- 0 – 0.5

and optionally conventional refining agents in customary amounts.

2. Borosilicate glass according to Claim 1,
characterized in that
it contains (in % by weight on an oxide basis)

SiO2 72.0 – 73.5
B2O3 8.3 – 9.5
Al2O3 5.0 – 6.0
Na2O 7.3 – 8.2
K2O 2.0 – 2.5
MgO 0 – 0.3
CaO 1.0 – 1.5
SrO 0.5 – 1.0
CeO2 0 – 0.3
F- 0 – 0.5

and optionally conventional refining agents in customary amounts.

3. Borosilicate glass according to Claim 1 or 2,
characterized in that
the ratio of the proportions by weight of K2O / Na2O is 0.24 – 0.35.

4. Borosilicate glass according to at least one of Claims 1 to 3 having a coefficient of thermal expansion ?(20°C; 300°C) in the range from 5.8 ? 10-6/K to 6.2 ? 10-6/K, a hydrolytic resistance HGA of class 1 and a processing temperature VA of not more than 1120?C.

5. Use of the borosilicate glass according to at least one of Claims 1 to 4 as pharmaceutical primary packaging.

6. Use according to Claim 5, wherein the borosilicate glass is used as pharmaceutical primary packaging for accommodating and storing liquid contents which have a pH in the range from 1 to 11, more preferably in the range from 4 to 9, very particularly preferably in the range from 5 to 7, where the liquid contents are preferably selected from among solutions of active compounds, buffer solutions or water for injection purposes.

7. Pharmaceutical primary packaging consisting of the borosilicate glass according to any of Claims 1 to 4.

8. Pharmaceutical combination comprising the pharmaceutical primary packaging according to Claim 7 which contains a liquid content having a pH in the range from 1 to 11, more preferably in the range from 4 to 9, very particularly preferably in the range from 5 to 7, where the liquid content is preferably selected from among a solution of an active compound, buffer solution or water for injection purposes.
, Description:Description

The invention relates to a barium-free borosilicate glass. The invention also relates to the use of the glass. For use as pharmaceutical primary packaging such as ampoules or bottles, glasses which have, in particular, a very high hydrolytic resistance are required. An important parameter for characterizing the processability of a glass is the processing temperature VA at which the viscosity of the glass is 104 dPas. It should be low because even slight VA reductions lead to a significant decrease in the production costs because the melting temperatures can be decreased. For glasses to be used as pharmaceutical primary packaging, it should also be low because vaporization of alkali metal borate occurring during shaping of the alkali metal-containing borosilicate glasses is then very low. These outgassing products form deposits specifically in glass containers produced from tube and have an adverse effect on the hydrolytic resistance of the containers.

The patent literature has described glasses which have a high chemical stability but have disadvantageously high processing temperatures.

The patent document DE 42 30 607 C1 discloses chemically highly resistant borosilicate glasses which are low in alkali metals and Al2O3 and can be fused with tungsten. They have coefficients of expansion ?(20°C; 300°C) of not more than 4.5 ? 10-6/K and, according to the examples, have processing temperatures of ? 1210°C.

The glasses of the patent document DE 44 30 710 C1 have a high proportion of SiO2, namely > 75% by weight. Although they are highly chemically resistant, they have disadvantageously high processing temperatures.

The glasses having relatively high SiO2 contents and high K2O contents of the patent document DE 195 36 708 C1 are also highly chemically resistant but likewise have disadvantageously high processing temperatures and low thermal expansions ?(20°C; 300°C) of 4.9 ? 10-6/K.

The borosilicate glasses described in the first publication DE 37 22 130 A1 also have low expansions and high processing temperatures.

Glasses which have both the desired high chemical resistances and the desired advantageous low melting temperatures have also already been described in the patent literature. They usually contain BaO; see, for example, in DE 102 38 915 B3 in which glasses having a coefficient of thermal expansion in the range from 5.8 ? 10-6/K to 7.0 ? 10-6/K are described.

Since the glass component BaO has in recent years come under discussion, especially in the pharmaceutical industry, because there is a risk that in the case of particular packaged goods in the pharmaceutical primary packaging barium ions will dissolve from the glass and lead to precipitates and turbidity in the packaged goods, barium-free glasses which correspond in terms of the properties important for pharmaceutical primary packaging to the barium-containing glasses used hitherto should be made available on the market.

The simple replacement of the barium oxide by one or more constituents generally does not enable the desired glass-technical and product-relevant properties which are influenced by BaO to be reproduced. Instead, new developments or far-reaching changes in the glass composition are necessary.

Further glasses which are free of BaO or contain BaO only as optional component are also already known from the prior art. However, they have the wide variety of disadvantages of, or at least differences from, the abovementioned barium-containing glasses, so that they are not able to replace the latter because of their altered property profile.

DE 100 35 801 A1 describes optionally BaO-containing glasses having processing temperatures of up to 1180 °C.
US 4 386 164 and DE 33 10 846 A1 describe barium-free laboratory glasses having coefficients of linear expansion ?(0°C; 300°C) of from 4.8 ? 10-6/K to 5.6 ? 10-6/K.

It is then an object of the invention to discover a barium-free glass which has a coefficient of thermal expansion ?(20°C; 300°C) of about 6 ? 10-6/K and meets the abovementioned demanding requirements in respect of the hydrolytic resistance combined with a low processing temperature VA.

This object is achieved by the glass described in Claim 1.

The glass of the invention varies in terms of its composition only within very narrow limits.

For a chemically highly resistant glass, it has a relatively low SiO2 content of at least 71.0% by weight, preferably at least 72.0% by weight, and of not more than 74.5% by weight, preferably not more than 73.5% by weight. The relatively low SiO2 content has an advantageous effect on the desired properties, of a low processing temperature and a relatively high coefficient of thermal expansion of about 6 ? 10-6/K. A further reduction in the SiO2 content would, in particular, impair the acid resistance.

The glass contains at least 8.0% by weight of B2O3, preferably at least 8.3% by weight of B2O3, and not more than 9.5% by weight of B2O3, in order to lower the thermal expansion, the processing temperature and the melting temperature while at the same time improving the chemical resistance, in particular the hydrolytic resistance. The boric acid binds the alkali metal ions present in the glass more strongly into the glass structure, which leads to a smaller release of alkali in contact with solutions, for example in the determination of the hydrolytic resistance. While at lower contents the hydrolytic resistance would be significantly impaired and the melting temperature would not be decreased enough, the acid resistance would be impaired at higher contents.

The glass of the invention contains at least 4.6% by weight of Al2O3 and not more than 6.0% by weight of Al2O3, preferably at least 5.0% by weight of Al2O3. As a result, the glass is very crystallization-stable, i.e. no devitrification crystals which stay at the glass surface and would adversely affect shaping of the glass are formed during cooling in the shaping process, for example when drawing tubes. In a similar manner to boric acid, Al2O3 also binds the alkali metal oxides, in particular Na2O, more strongly into the glass. At higher contents, the melting temperature and the processing temperature would increase without the resulting better crystallization stability being of further use.

An important feature of the glass of the invention are the proportions of the alkali metal oxides Na2O and K2O within very narrow limits, which makes a balanced ratio between them possible. Lithium oxide can be present in an amount of up to 0.3% by weight. Although it lowers the processing temperature very effectively, namely by about 40°C per 1% by weight, it is very expensive, for which reason the use of Li2O is preferably dispensed with and the glass thus preferably does not contain any Li2O apart from unavoidable or difficult-to-avoid impurities.

Thus, the glass contains at least 7.0% by weight of Na2O, preferably at least 7.3% by weight of Na2O, and not more than 8.4% by weight of Na2O, preferably not more than 8.2% by weight of Na2O, and also at least 1.7% by weight of K2O, preferably at least 2.0% by weight of K2O, and not more than 2.7% by weight of K2O, preferably not more than 2.5% by weight of K2O.

The alkali metal oxides, in particular Na2O, reduce the processing temperature of the glass; in addition, K2O improves the devitrification stability. Above the respective upper limit of the alkali metal oxide, the release of alkali increases disproportionately. Thus, a minimum in the release of alkali is achieved by the specific proportions, which leads to the various excellent chemical resistances.

Particular preference is given to the ratio of the proportion by weight of K2O / Na2O being 0.24 – 0.35. The undesirable release of alkali is minimized in this way.

The glass does not contain any BaO apart from unavoidable or difficult-to-avoid impurities. As a result, leaching of barium ions and precipitation of barium salts cannot occur on contact with liquids, in particular aqueous solutions.

The glass contains SrO, in fact at least 0.4% by weight, preferably at least 0.5% by weight, and not more than 1.2% by weight, preferably not more than 1.0% by weight. The melting temperature is in this way decreased as desired. More SrO than the upper limit indicated would increase the release of alkali. Too little or even omission of SrO would let the melting temperature increase.

The glass contains CaO, in fact at least 0.8% by weight, preferably at least 1.0% by weight, and not more than 1.6% by weight, preferably not more than 1.5% by weight. It can contain 0 – 0.3% by weight of MgO as further component. Particular preference is given to the glass being MgO-free apart from unavoidable or difficult-to-avoid impurities. CaO and MgO vary the “length of the glass”, i.e. the temperature range in which the glass is processable. Due to the differently strong network-transforming action of these components, the viscosity behaviour can be adapted to the requirements of the respective production and processing process by replacement of these oxides by one another. In addition, CaO improves the acid resistance. CaO and MgO decrease the processing temperature and are, if present, firmly bound into the glass structure. The sum CaO + SrO + MgO should preferably not exceed 2.5% by weight since otherwise the release of alkali would increase.

The glass can contain 0 – 0.5% by weight of ZrO2. ZrO2 improves the hydrolytic resistance and especially the alkali resistance of the glass. At higher proportions, the processing temperature would be increased too greatly and the good fusibility would be lost. The glass particularly preferably does not contain any ZrO2 apart from unavoidable or difficult-to-avoid impurities.

The glass can contain 0 – 0.5% by weight of TiO2. When used to replace SiO2, TiO2 reduces the processing temperature. At higher proportions, a brownish discoloration of the glass would occur. The glass particularly preferably does not contain any TiO2 apart from unavoidable or difficult-to-avoid impurities.

The glass can contain 0 – 1% by weight of CeO2. In low concentrations, CeO2 acts as refining agent, and in higher concentrations it prevents discoloration of the glass by radioactive radiation. Primary packaging which has been produced using such a CeO2-containing glass and filled can therefore be inspected visually for any particles present even after being subjected to radioactivity. Higher CeO2 concentrations make the glass more expensive and lead to an undesirable yellow-brownish intrinsic coloration. For applications in which the ability to avoid discoloration due to radioactive radiation is not important, preference is given to a CeO2 content in the range from 0 to 0.3% by weight.

Furthermore, the glass can contain 0 – 0.6% by weight of F-. This reduces the viscosity of the melt, which accelerates melting of the mix and refining of the melt. In addition, buffering of the pH of an aqueous solution in contact with the glass is achieved with increasing F content. That is to say, the rise in the pH in the fill material generated by the release of alkali from the inner glass surface after packaging of materials for injection in glass containers is partially neutralized by F ions.

The glass can be refined using, apart from the abovementioned fluorides, for example CaF2, conventional refining agents such as chlorides, for example NaCl, and/or sulfates, for example Na2SO4 or BaSO4, or else using CeO2, which are present in customary amounts, i.e. in amounts of from 0.001 to 1% by weight, depending on the amount and type of refining agent used, in the finished glass. When As2O3 and Sb2O3 are not used, the glasses are As2O3- and Sb2O3-free except for unavoidable impurities, which is particularly advantageous for use thereof as pharmaceutical primary packaging.

The barium-free borosilicate glass of the invention thus contains (in % by weight on an oxide basis)

SiO2 71.0 – 74.5
B2O3 8.0 – 9.5
Al2O3 4.6 – 6.0
Na2O 7.0 – 8.4
K2O 1.7 – 2.7
Li2O 0 – 0.3
MgO 0 – 0.3
CaO 0.8 – 1.6
SrO 0.4 – 1.2
TiO2 0 – 0.5
ZrO2 0 – 0.5
F- 0 – 0.6
CeO2 0 – 1.0

and also conventional refining agents in customary amounts.

Preference is given to the glass consisting essentially of the components mentioned in the proportions mentioned; particular preference is given to the glass consisting of the components mentioned in the proportions mentioned.

The barium-free borosilicate glass of the invention preferably contains (in % by weight on an oxide basis)

SiO2 72.0 – 73.5
B2O3 8.3 – 9.5
Al2O3 5.0 – 6.0
Na2O 7.3 – 8.2
K2O 2.0 – 2.5
MgO 0 – 0.3
CaO 1.0 – 1.5
SrO 0.5 – 1.0
CeO2 0 – 0.3
F- 0 – 0.5

and optionally conventional refining agents in customary amounts.

Preference is given to the glass consisting essentially of the components mentioned in the proportions mentioned; particular preference is given to the glass consisting of the components mentioned in the proportions mentioned.

Two examples of a glass (A) according to the invention and five comparative examples (V) were melted from conventional raw materials.

Table 1 reports the respective composition (in % by weight on an oxide basis), the coefficient of thermal expansion ?(20°C; 300°C) ?10-6/K?, the glass transition temperature Tg ??C?, the processing temperature VA ??C?, the density ? [g/cm3] and the hydrolytic resistance of the glasses.

The hydrolytic resistance was determined as follows:

• The hydrolytic resistance HGB in accordance with ISO 719. The figure reported is in each case the base equivalent of the acid consumption in ?g of Na2Oeq/g of glass grains. The maximum value for a chemically highly resistant glass of hydrolytic class 1 is 31 ?g of Na2Oeq/g of glass.
• The hydrolytic resistance HGA in accordance with ISO 720 or USP. The figure reported is in each case the acid consumption per g of glass grains. The maximum value for a chemically highly resistant glass of hydrolytic class 1 is 0.1 ml/g of glass.

In the case of the hydrolytic resistance HGB which is particularly important for pharmaceutical purposes, the glasses having base equivalents of ? 19 µg of Na2O/g, which do not belong to class 1 but represent low values even within HGB = 1, give very good results.

The glasses of the invention are therefore outstandingly suitable for all applications in which chemically resistant glasses are required, e.g. for laboratory applications, for chemical plants, for example as tubes, and in particular as containers for medical purposes, for pharmaceutical primary packaging such as ampoules, bottles, syringes or cartridges.

Furthermore, it has been found that the glasses of the invention display good chemical resistance in contact with liquid contents, e.g. solutions of active compounds, solvents, e.g. buffer systems, or the like which are present in the pH range from 1 to 11, more preferably in the pH range from 4 to 9, very particularly preferably in the pH range from 5 to 7, and are therefore particularly well suited for storage or keeping in stock of these contents.

The glasses of the invention are thus outstandingly suitable for producing pharmaceutical containers which are in contact with contents and can therefore be provided for accommodation and storage thereof. Contents which can be used are, for example, all solid and liquid compositions used in the pharmaceutical sector.

Contents which may be mentioned by way of example, without implying a restriction to these: a liquid medicament preparation, a solution comprising one or more active compounds and optionally of auxiliary and additives, buffer systems of all types, e.g. sodium bicarbonate buffers such as a 1 molar sodium bicarbonate solution (NaHCO3) 8.4% having a pH in the range from 7.0 to 8.5; citrate buffers such as 10 mmol citrate buffer pH = 6 with 150 mmol of NaCl and 0.005% of Tween 20; phosphate buffers such as 10 mmol phosphate buffer pH = 7.0 with 150 mmol of NaCl and 0.005% of Tween 20, or water for injection purposes, e.g. Sartorius high-purity water, flushed through a 0.2 µm filter and having a specific resistance of 18.2 MO ? cm (corresponds to a conductivity of 0.055 µS/cm). Further possible contents will be readily apparent to a person skilled in the art.

The invention also provides for the use of the borosilicate glasses of the invention as pharmaceutical primary packaging for accommodating and storing liquid contents which have a pH in the range from 1 to 11, more preferably in the range from 4 to 9, very particularly preferably in the range from 5 to 7, where the liquid contents are preferably selected from among solutions of active compounds, buffer solutions or water for injection purposes. The invention also provides such pharmaceutical primary packaging.

The invention also provides a pharmaceutical combination comprising the pharmaceutical primary packaging which contains a liquid content having a pH in the range from 1 to 11, more preferably in the range from 4 to 9, very particularly preferably in the range from 5 to 7, where the liquid content is preferably selected from among a solution of an active compound, buffer solution or water for injection purposes.

The very low processing temperatures VA of not more than 1120?C characterize the good processability of the glasses. The melting temperatures of the glasses are very low. They are about 1560°C. The favourable melting and processing range brought about thereby reduces the energy consumption in the production process.

The glasses are free of BaO and in a preferred embodiment free of As2O3 and Sb2O3, which is particularly advantageous for use as pharmaceutical primary packaging. Even without the presence of BaO, a sufficiently low processing temperature is achieved without the hydrolytic resistance being impaired.

The glasses have a glass transition temperature Tg of about 560°C.
It is in the normal range for pharmaceutical glasses.

The glasses have a coefficient of thermal expansion ?(20°C; 300°C) in the range from 5.8 ?10-6/K to 6.2 ? 10-6/K.
In terms of their linear expansion, they are therefore in the same range as the barium-containing glasses which they are to replace.

The glasses also have a crystallization stability which is satisfactory for tube drawing.

Table 1:

Compositions (in % by weight on an oxide basis) of the working examples (A1, A2) and the comparative examples (V1 – V5) and the significant properties thereof:

A1 A2 V1 V2 V3 V4 V5
SiO2 72.8 73.4 72.2 73.5 74.85 74.85 72.0
B2O3 9.0 9.0 9.1 8.6 8.95 9.0 8.75
Al2O3 5.5 5.5 5.9 5.0 4.8 4.8 4.7
Na2O 7.9 7.7 7.9 7.9 8.2 7.6 6.3
K2O 2.3 2.1 2.3 1.8 1.9 2.45 2.8
MgO - - - - 0.3 0.2 0.2
CaO
SrO 1.4
0.8 1.2
0.8 1.9
0.4 0.7
2.5 0.7
- 0.8
- 1.1
-
BaO - - - - - - 3.75
F- 0.3 0.3 0.3 - 0.3 0.3 0.4
?(20°C;300°C)
?10-6/K? 6.08 5.96 6.09 6.01 6.08 6.08 6.05
Tg ??C? 558 555 546 566 557 557 557
VA ??C?
? [g/cm3]
USP/ISO720 titrated
HGA class 1100
2.38
0.058

1 1118
2.38
0.050

1 1104
n.d.
0.067

1 1113
n.d.
0.072

1 1120
2.38
0.056

1 1120
n.d.
0.056

1 1105
2.45
0.058

1
HGB ??g of Na2O/g glass? 17 15 20 22 16 16 17
n.d. = not determined

The working examples clearly show that despite being free of BaO the glasses of the invention combine a very low processing temperature and a very good hydrolytic resistance, two properties which have hitherto not been able to be combined with one another in the known BaO-free glasses having the desired expansion. They are comparable in terms of their properties and therefore compatible in production with the BaO-containing comparative example V5, but with the advantage of freedom from BaO and therefore particular suitability for pharmaceutical primary packaging. The two working examples demonstrate the relationship between release of alkali and processing temperature. Thus, depending on requirements and within the boundaries of the present invention, either the processing temperature or the release of alkali can be lowered, in each case at the justifiable expense of the other parameter.