JP6075600B2 - Glass for pharmaceutical containers and glass tube using the same - Google Patents

Description

  The present invention relates to glass and glass tubes used for producing pharmaceutical containers.

  Conventionally, various glasses have been used as materials for filling containers for storing pharmaceuticals. Pharmaceuticals are roughly classified into oral preparations and injections, and the type of glass used for the filling container is selected according to the classification.

  Oral preparations are filled in containers in various forms such as drinks and tablets. Since these oral preparations are absorbed into the body through the digestive tract, in many cases, the required management quality is not as high as that of an injection and the quality required for a storage container is not high. Therefore, it is only necessary that the oral filling container be able to block moisture, oxygen in the air, or ultraviolet rays from the oral preparation, and generally inexpensive soda lime glass is used.

  On the other hand, since an injection is directly administered into the body from a blood vessel or the like, a very strict quality is required for the filling container. Specifically, in order to prevent alteration of the filled medicine, it is required not only to block moisture, oxygen and ultraviolet rays in the air, but also to prevent components such as alkali metals constituting the container from being easily eluted into the medicine. . From such a demand, borosilicate glass has been conventionally used as a material for filling containers for injections (for example, Patent Document 1). The borosilicate glass disclosed in Patent Document 1 is less likely to elute alkali metal components in the glass than soda lime glass and the like, and it is difficult to alter the chemicals to be filled.

JP-A-7-206472

  In addition to the above requirements, high performance is required for glass for pharmaceutical containers. For example, it is preferable that the glass for pharmaceutical containers has high mechanical strength from the viewpoints of safety, cost of loss at breakage, and the like. In general, it is known that the mechanical strength of glass is significantly reduced when scratched. And, conventional injectable containers such as ampoules, vials, prefilled syringes, cartridges, etc. may be damaged in each process such as container processing, inspection, transportation, drug filling, etc., causing the strength of the container to decrease. .

  In view of such problems, an object of the present invention is to provide a glass and a glass tube that have a small amount of elution of an alkali metal component that affects a filled medicine, are hardly scratched, and are not easily broken. .

As a result of intensive studies, the present inventors have found that the above technical problem can be solved by regulating the glass composition within a predetermined range, and propose the present invention. That is, the glass for pharmaceutical containers of the present invention has, as a glass composition, mass%, SiO ₂ 50 to 70%, B ₂ O _{3 0 to} 15%, Al ₂ O ₃ 10 to 20%, MgO 0 to 5%, It contains 0 to 10% of CaO, 0 to 10% of SrO, and 0 to 10% of BaO, and does not contain an alkali metal component. Incidentally, "containing no alkali metal component" refers to the total amount _{Li 2 O + Na 2 O +} K 2 O alkali metal components contained is less than 0.1%.

  Second, the glass for a pharmaceutical container of the present invention preferably has a crack resistance value of 700 gf or more. Crack resistance is an index of how easily glass is damaged. More specifically, the crack resistance is a crack that can occur at the maximum when the Vickers indenter is pressed with various loads for 15 seconds and the number of cracks generated from the four corners of the indentation is counted by 15 seconds excluding the diamond indenter. The load when the ratio to the number (4) is 50% is shown.

Third, the glass for a pharmaceutical container of the present invention preferably has a liquidus viscosity of 10 ^4.5 dPa · s or more. Here, the liquid phase viscosity refers to a value obtained by measuring the viscosity of glass at the liquid phase temperature by a platinum ball pulling method. The liquidus temperature is measured by measuring the temperature at which crystals precipitate after passing through a standard sieve 30 mesh (500 μm), putting the glass powder remaining on 50 mesh (300 μm) into a platinum boat and holding it in a temperature gradient furnace for 24 hours. Indicates the value.

Fourthly, it is preferable that the glass for pharmaceutical containers of the present invention has a thermal expansion coefficient of 30 to 45 × 10 ⁻⁷ / ° C. at 30 to 380 ° C.

  Fifth, the glass for pharmaceutical containers of the present invention has a consumption amount of hydrochloric acid of 0.03 ml used in neutralization titration in an alkali dissolution test measured based on the water resistance test method described in European Pharmacopoeia 7.0 edition 3.2. / G · glass or less is preferable. The hydrochloric acid consumption is proportional to the alkali elution amount of the glass, and it can be said that the smaller the hydrochloric acid consumption, the smaller the alkali elution amount of the glass.

Sixth, it is preferable to further contain 0.1 to 1% of glass container glass SnO ₂ of the present invention.

  Seventh, it is preferable that the glass tube of the present invention is made of the glass for a pharmaceutical container.

  According to the glass for pharmaceutical containers of the present invention, it is possible to obtain a glass that is less likely to be scratched and hard to break than conventional products while suppressing the elution amount of the alkali metal component. More specifically, since the glass for a pharmaceutical container of the present invention does not substantially contain an alkali metal oxide, it can suppress alkali elution into the drug. Therefore, when the glass for a pharmaceutical container of the present invention is used as a drug filling container, it is possible to suppress the quality change of the drug due to alkali elution and keep the drug quality good. Furthermore, since the glass for pharmaceutical containers of the present invention has the above composition, it has high crack resistance. Therefore, the glass for pharmaceutical containers of the present invention is hardly scratched and is not easily damaged.

Pharmaceutical container glass of the present invention, as a glass composition, in _{mass%, SiO 2 50~70%, B} 2 O 3 0~15%, Al 2 O 3 10~20%, 0~5% MgO, CaO 0 -10%, SrO 0-10%, BaO 0-10% is included, and an alkali metal oxide is not included substantially. The reason for limiting the content range of each component as described above will be described below. In the description of the composition range below,% display represents mass% unless otherwise specified.

SiO ₂ is a component that forms a network of glass, and the content of SiO ₂ is 50 to 70%. When the content of SiO ₂ is less than 50%, the water resistance of the glass tends to deteriorate or the crack resistance tends to decrease. When the content of SiO ₂ is more than 70%, the meltability and moldability tend to be lowered. The preferable range of the content of SiO ₂ is 55 to 70%, more preferably 55 to 68%, and most preferably 57 to 65%.

B ₂ O ₃ is a component that forms a glass network, and the content of B ₂ O ₃ is 0 to 15%. When the content of B ₂ O ₃ is more than 15%, the amount of change in viscosity with respect to the amount of change in temperature increases, making it difficult to mold the glass. Moreover, when the content of B ₂ O ₃ exceeds 15%, the amount of components that volatilize from the surface of the melting kiln when the glass raw material is melted increases, and defects such as blisters are likely to occur in the glass. The preferable range of the content of B ₂ O ₃ is 0 to 13%, more preferably 3 to 13%, and most preferably 5 to 12%.

Al ₂ O _{3 is} also a component that forms a glass network, and the content of Al ₂ O ₃ is 10 to 25%. When the content of Al ₂ O ₃ is less than 10%, the water resistance of the glass tends to deteriorate. When the content of Al ₂ O ₃ is more than 25%, the viscosity of the glass is increased, and the temperature for melting the glass and the temperature for forming the glass are increased, resulting in a problem that the production energy cost is increased. The preferable range of the content of Al ₂ O ₃ is 12 to 23%, more preferably 13 to 22%, and most preferably 15 to 20%.

  MgO is a component that adjusts the thermal expansion coefficient of glass and lowers the high-temperature viscosity. The content of MgO is 0 to 5%. When the content of MgO is more than 5%, the crack resistance is lowered and the glass is easily broken. Further, if the content of MgO exceeds 5%, the coefficient of thermal expansion increases, so that the possibility of breakage due to thermal shock in the glass manufacturing process or the like increases. The preferable range of the content of MgO is 0 to 4%, more preferably 0 to 3%.

  CaO is a component that adjusts the thermal expansion coefficient of glass and lowers the high-temperature viscosity. The content of CaO is 0 to 10%. When the content of CaO is more than 10%, the crack resistance is lowered and the glass is easily broken. Moreover, since the coefficient of thermal expansion will become high when content of CaO exceeds 10%, possibility that it will be damaged by the thermal shock in a glass manufacturing process becomes high. The preferable range of the content of CaO is 2 to 10%, more preferably 3 to 10%, and most preferably 3 to 8%.

  SrO is a component that adjusts the thermal expansion coefficient of glass and lowers the high-temperature viscosity. The content of SrO is 0 to 10%. When the content of SrO is more than 10%, the crack resistance is lowered and the glass is easily broken. On the other hand, if the SrO content exceeds 10%, the thermal expansion coefficient increases, so that the possibility of breakage due to a thermal shock in the glass manufacturing process increases. The preferable range of the content of SrO is 0 to 8%, more preferably 0.5 to 8%.

  BaO is a component that adjusts the thermal expansion coefficient of glass and lowers the high-temperature viscosity. The content of BaO is 0 to 10%. When the content of BaO is more than 10%, the crack resistance is lowered and the glass is easily broken. Moreover, since the coefficient of thermal expansion will become high when content of BaO exceeds 10%, possibility that it will be damaged by the thermal shock in a glass manufacturing process becomes high. The preferable range of the content of BaO is 0 to 8%, more preferably 0 to 7%, and most preferably 0.5 to 6%.

The pharmaceutical glass of the present invention may further contain components such as ZnO, Sb ₂ O ₃ , As ₂ O ₃ , SnO ₂ , Cl, and F in addition to the above components.

  ZnO is a component that adjusts the thermal expansion coefficient of glass and lowers the high-temperature viscosity, and the content of ZnO is preferably 0 to 5%. When the ZnO content is more than 5%, the crack resistance is lowered and the glass is easily broken. Moreover, since the thermal expansion coefficient will become high when content of ZnO exceeds 5%, possibility that it will be damaged by the thermal shock in a glass manufacturing process becomes high. A more preferable range of the content of ZnO is 0 to 4%, more preferably 0 to 3%, and most preferably 0 to 2%.

Sb ₂ O ₃ and As ₂ O ₃ are components that improve clarity (foaming) during glass melting, and the contents of Sb ₂ O ₃ and As ₂ O ₃ are each preferably 0 to 1%. . If the content of Sb ₂ O ₃ and As ₂ O ₃ is more than 1%, Sb and As may be reduced and precipitated as a colloid during glass processing, and the glass may be colored. A more preferable range of the contents of Sb ₂ O ₃ and As ₂ O ₃ is 0 to 0.8%, more preferably 0 to 0.6%, and most preferably 0 to 0.5%.

SnO ₂ is a component to improve the clarity of the glass during melting, the content of SnO ₂ is preferably 0 to 1%. If the SnO ₂ content is more than 1%, Sn may be reduced during glass processing and deposited as a colloid, and the glass may be colored. A more preferable range of the content of SnO ₂ is 0.1 to 0.5%, more preferably 0.1 to 0.3%, and most preferably 0.1 to 0.3%.

  Cl is a component that improves the clarity during glass production, and the Cl content is preferably 0 to 1%. If the Cl content is more than 1%, Cl evaporated during glass production may react with moisture and corrode the metal in the production facility. A more preferable range of the Cl content is 0 to 0.5%, more preferably 0 to 0.3%, and most preferably 0.01 to 0.3%.

  F is a component that improves the clarity when glass is melted, and the content of F is preferably 0 to 1%. Since F is a substance with a high environmental load, it is preferable to suppress the usage amount as much as possible. A more preferable range of the content of F is 0 to 0.5%, more preferably 0 to 0.3%, and most preferably 0 to 0.2%.

In addition to the above components, other components may be added as long as the effects of the present invention are not significantly impaired. For example, 0 to 5% of ZrO ₂ may be added to improve heat resistance, and 0 to 5% of TiO ₂ may be added to shield ultraviolet rays.

  The value of crack resistance of the glass for pharmaceutical containers of the present invention is preferably 700 gf or more, more preferably 800 gf or more, still more preferably 900 gf or more, and most preferably 1000 gf or more. The value of the crack resistance is a numerical value that indicates how easily glass is damaged. When the crack resistance value is lower than 700 gf, the glass tends to be damaged when molding glass and when processing and manufacturing containers such as ampoules, vials, and prefilled syringes from glass, and the mechanical strength of the glass tends to decrease. .

The liquid viscosity of the glass for a pharmaceutical container of the present invention is preferably 10 ^4.5 dPa · s or more. The liquid phase viscosity is more preferably 10 ^4.8 dPa · s or more, further preferably 10 ^5.0 dPa · s or more, and most preferably 10 ^5.3 dPa · s or more. If the liquid phase viscosity is lower than 10 ^4.5 dPa · s, it becomes difficult to form a glass using the Danner method or the like, so that it is difficult to produce the glass tube for a pharmaceutical container of the present invention in a large amount and at a low cost.

The glass for a pharmaceutical container of the present invention preferably has a thermal expansion coefficient of 30 to 45 × 10 ⁻⁷ / ° C. at 30 to 380 ° C. The coefficient of thermal expansion refers to the value measured using a dilatometer. Thermal expansion coefficient, more preferably 30 to 40 × ^{10 -7} / ° C., more preferably 30~38 × ^{10 -7} / ℃, and most preferably 32~38 × ^{10 -7} / ℃. When the thermal expansion coefficient is lower than 30 × 10 ⁻⁷ / ° C., the viscosity of the glass tends to increase, and the melting temperature and the molding temperature increase to make it difficult to produce the glass. Moreover, if the thermal expansion coefficient is higher than 45 × 10 ⁻⁷ / ° C., there is a high possibility of breakage due to thermal shock in the glass manufacturing process, processing process, sterilization process, and the like.

  The glass for pharmaceutical containers of the present invention is neutralized in a water resistance test described in European Pharmacopeia 7.0 version 3.2 (European Pharmacopeia 7.0 3.2 Containers, 3.2.1 Glass containers for pharmaceutical us, Test B. Hydrolytic resistance of glass grains). The consumption of hydrochloric acid used in the titration is preferably 0.03 ml / g · glass or less. If the amount of hydrochloric acid consumed is greater than 0.03 ml / g · glass, that is, if the amount of alkali elution from the glass is large, when the glass for a pharmaceutical container is used as a pharmaceutical container, the charged medicine tends to be easily altered. is there. Therefore, the consumption of hydrochloric acid is more preferably 0.02 ml / g · glass or less, and most preferably 0.01 ml / g · glass or less.

  The manufacturing method of the glass tube for pharmaceutical containers of this invention is illustrated. The Danner method is suitable as a method for producing the glass tube for a pharmaceutical container of the present invention. First, glass raw materials are prepared so as to have the above glass composition, and a glass batch is prepared. Next, the glass batch was continuously charged into a melting furnace at 1550 to 1700 ° C., melted and clarified, and then the obtained molten glass was wound around a rotating refractory while blowing air from the tip of the refractory, Pull out the glass tube from the tip. In addition, the manufacturing method of the glass tube for pharmaceutical containers of this invention is not restricted to the Danner method, You may use the conventionally well-known arbitrary methods. For example, the bellows method is also an effective method for producing the glass tube for a pharmaceutical container of the present invention.

  Hereinafter, based on an Example, this invention is demonstrated in detail. The following examples are merely illustrative, and the present invention is not limited to the following examples. Table 1 shows Examples (Sample Nos. 1 to 7) and Comparative Examples (Sample No. 8) of the present invention.

  First, after preparing a glass raw material so that it might become a glass composition of Table 1, the obtained glass batch was put into the platinum crucible, and it melted at 1600-1700 degreeC for 4 hours. Next, after the obtained molten glass was poured out on a carbon plate and formed into a plate shape, a predetermined annealing treatment (furnace cooling in an electric furnace set at 650 ° C.) was performed. Finally, various properties of the obtained glass samples were evaluated.

  A thermal expansion coefficient is the value which measured the average linear thermal expansion coefficient in the temperature range of 30-380 degreeC using the dilatometer.

  The strain point and annealing point are values measured based on the method of ASTM C336.

  The softening point is a value measured based on the method of ASTM C338.

Temperature ^T10 4.0 in high temperature viscosity ¹⁰ 4.0 dPa · ^{s, 10} 3.0 Temperature ^T10 3.0 in dPa · ^{s, 10} 2.5 Temperature ^{10 2.5} in dPa · s are each platinum ball pulling method It is the value measured by.

  The liquid phase temperature passed through a standard sieve 30 mesh (500 μm), the glass powder remaining in 50 mesh (300 μm) was placed in a platinum boat, held in a temperature gradient furnace for 24 hours, and then the temperature at which crystals precipitated was measured. Points to the value.

  The liquid phase viscosity is a value obtained by measuring the viscosity of the glass at the liquid phase temperature using a platinum ball pulling method.

  Hydrochloric acid consumption in the water resistance test was measured based on European Pharmacopeia 7.0 edition 3.2 (European Pharmacopeia 7.0 3.2 Containers, 3.2.1 Glass containers for pharmaceutical us, Test B. Hydrolytic resistance of glass grains).

  The crack resistance of the glass was determined by the method proposed by Wada et al. (M. Wada et al. Proc., The Xth ICG, vol. 11, Ceram. Soc., Japan, Kyoto, 1974, p39). In this method, a plate-shaped sample glass is placed on the stage of a Vickers hardness tester, and a diamond-shaped diamond indenter is pressed against the surface of the sample glass with various loads for 15 seconds. Then, the number of cracks generated from the four corners of the indentation by 15 seconds excluding the diamond indenter was counted, and the ratio to the maximum number of cracks that could be generated (4 pieces) was determined to be the crack generation rate. Further, the load when the crack occurrence rate was 50% was defined as “crack resistance”. As the crack resistance is larger, the crack is less likely to occur and the glass is less likely to be damaged. The crack occurrence rate was measured 20 times with the same load, and obtained from the average value. In addition, since crack resistance is affected by humidity, measurement was performed under conditions of an air temperature of 25 ° C. and a humidity of 30%.

  As shown in Table 1, sample no. Nos. 1 to 7 were glasses with a consumption of hydrochloric acid of 0.01 ml / g · glass or less and little alkali elution. On the other hand, sample No. No. 8 was a glass having a hydrochloric acid consumption of 0.04 ml / g · glass and a large amount of alkali elution. Sample No. Nos. 1 to 7 were glasses having a crack resistance of 1000 gf or more and hardly scratched. On the other hand, sample No. No. 8 was a glass having a crack resistance of 600 gf and easily damaged.

  The glass tube for a pharmaceutical container of the present invention is useful as a material for a pharmaceutical container.

Claims (6)

By _{mass%, SiO 2 50~70%, B} 2 O 3 0~15%, Al 2 O 3 10~20%, MgO 0~2.5%, CaO 2 ~10%, SrO 0~10%, BaO A glass for pharmaceutical containers, containing 0 to 10%, substantially free of alkali metal oxides, and having a tubular shape.   The glass for pharmaceutical containers according to claim 1, wherein the crack resistance value is 700 gf or more. Liquid phase viscosity is 10 < ^4.5 > dPa * s or more, Glass for pharmaceutical containers of Claim 1 or 2 characterized by the above-mentioned. The glass for pharmaceutical containers according to any one of claims 1 to 3, wherein a coefficient of thermal expansion at 30 to 380 ° C is 30 to 45 × 10 ^-7 / ° C. The amount of hydrochloric acid used in neutralization titration in the water resistance test described in European Pharmacopoeia 7.0, 3.2, is 0.03 ml / g · glass or less, according to any one of claims 1 to 4, The glass for pharmaceutical containers as described. Further pharmaceutical container glass according to claim 1, the SnO _2, characterized in that it contains 0.1 to 1 wt%.