JPH04325156A - Production of freeze dried solid - Google Patents

Abstract

PURPOSE:To provide the process for producing freeze dried solids which shortens the time required for freezing and drying and has a good handling characteristic. CONSTITUTION:A soln. is packed into dent parts of an aluminum sheet having >=1 dents and is freeze dried to form the freeze dried solids which are destroyed in >=30 seconds by water. A sheet to serve as a cap is thereafter put on thereon and is hermetically sealed. Since this freeze drying method uses aluminum having a good thermal conductivity as containers, the time required for the freezing and drying can be shortened and since the operations up to the hermetic sealing of the containers are integrally carried out, the handling characteristic is excellent.

Description

[Detailed description of the invention]

0001

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a freeze-drying method and a package of freeze-dried solid products.

0002

BACKGROUND OF THE INVENTION Freeze-dried solids generally have excellent solubility in water, but are very brittle and easily disintegrated, making them difficult to apply to normal packaging processes. For this reason, the special public official
2008 discloses a method for packaging lyophilized molded articles that can rapidly disintegrate in water into recessed sheets of film material.

0003

[Problem to be solved by the invention] Japanese Patent Publication No. 63-5200
The dimpled sheet of film material disclosed in No. 8 has the disadvantage of long freeze-drying times and high production costs due to poor thermal conductivity. In addition, freeze-dried molded products that rapidly disintegrate in water are very susceptible to collapse, so they have the disadvantage that they lose their shape during transportation or when taken out of the package.

0004

[Means for Solving the Problems] In the freeze-drying of a liquid containing a drug, the present invention involves filling the recesses of an aluminum sheet having one or more recesses with the liquid, and then freeze-drying the aluminum sheet for 30 minutes with water. A freeze-drying method characterized by forming a freeze-dried solid that disintegrates in seconds or more, then covering the aluminum sheet with a sheet that serves as a lid and bringing it into close contact with the aluminum sheet, and a package of the freeze-dried solid. It provides: In the freeze-drying method of the present invention, since the container is made of aluminum, which has good thermal conductivity, the time required for freezing and drying is shortened, and the freeze-drying method can be sealed in the container without taking out the freeze-dried solids one by one. The dry solids also have a high density, so they won't fall apart when being transported or opened. It is an object of the present invention to provide a method and package for producing a freeze-dried solid product that shortens the time required for freeze-drying and is easy to handle.

[0005] In the present invention, the density of the freeze-dried solid that disintegrates in water in 30 seconds or more is 250 mg/ml or more, and the hardness is 1.5 k when measured with a Kiya type hardness tester.
g or more. The composition of the freeze-dried solid is not particularly limited, and examples include compositions in which sugars are added to an aqueous solution containing a water-soluble drug, and compositions in which a fat-soluble drug is emulsified with an emulsifier and hardness enhancers such as skim milk powder. It is possible to use a composition that adds . In order to increase the density of the freeze-dried solid, it is effective to add sugars such as mannitol and sucrose, and hardness enhancers such as skim milk powder and locust bean gum.

[0006] The aluminum sheet having one or more depressions in the present invention is most preferably made of aluminum alone, but it is also possible to use a sheet having a multilayer structure of aluminum and a polymeric material. In addition, the sheet that becomes the lid can be made of aluminum alone, aluminum sheet with a multilayer structure of aluminum and film, polyvinyl chloride, polypropylene, polyvinyl chloride/polyvinylidene chloride,
Polyvinyl chloride/polytetrafluoroethylene or polyvinyl chloride/polyvinylidene chloride/polyethylene laminates and the like can be used.

[0007] In the present invention, the contents can be taken out from a package containing freeze-dried solids by pushing the bulge containing the solids and breaking the lid, as in the case of ordinary PTP packaging. can. If the freeze-dried solid is insufficient in hardness, it may be taken out by peeling off the lid. The freeze-dried solid may be taken as is and dissolved in the oral cavity, or may be swallowed as a solid. Also,
It may be taken by dispersing it in water before use.

[0008] The freeze-dried solid product of the present invention can be produced as follows. A solution in which the drug and other necessary excipients are dissolved, suspended or emulsified is filled into an aluminum sheet with depressions and frozen. After freezing, the solvent is sublimed under reduced pressure. At this time, drying time can be shortened by heating the frozen filling liquid to such an extent that it does not dissolve. After drying, without taking out the solids one by one, a sheet to serve as a lid is placed over the aluminum sheet with the depressions, and the sheet is tightly attached by heat. In the case of materials that are difficult to adhere to due to heat, they can be adhered with adhesive or the like.

[0009]

[Operation] In the freeze-drying method according to the present invention, a solution is filled into an aluminum sheet with good thermal conductivity, and freeze-drying is carried out.
The time required for freezing and drying is shortened. Furthermore, since the freeze-dried solids can be sealed without being taken out one by one, the freeze-dried solids can be easily packaged.

0010

Effects of the Invention In Example 1, the temperature of the emulsified dispersion was measured when the emulsified dispersion was frozen. -20 from room temperature
The time required to cool down to ℃ was 51 minutes when using the aluminum sheet according to the present invention, while it was 67 minutes when conventionally used vinyl chloride was used. It has become clear that freezing time can be shortened.

[0011]

【Example】

Example 1 To 1 g of ubidecarenone, 1 g of octyldodecylglyceride and 2.5 ml of ethanol were added and dissolved by heating. Separately, 0.5 g of lecithin and 0 sucrose fatty acid ester
．． 5 g was added to water containing 5% ethanol and dispersed with an ultrasonic homogenizer while heating. Next, the previously prepared ubidecarenone solution was added and thoroughly emulsified and dispersed using an ultrasonic homogenizer. To this emulsified dispersion, 8 g of sucrose, 13 g of mannitol, 1.5 g of gum arabic, 2 g of skim milk powder, 0.5 g of locust bean gum and 50 g of water were added.
ml and sufficiently emulsified and dispersed using a Polytron (trademark) to obtain a filling liquid. Pour this filling liquid into a hollow aluminum seal.
The mixture was filled in 1 ml portions and freeze-dried. After the solvent has completely sublimated, an aluminum sheet is placed on the recessed aluminum sheet to serve as a lid without removing the solids, and heated to make it adhere tightly to the lower aluminum sheet, sealing the lid and allowing the freeze-dried solids to be contained. I got a new package.

Claims (5)

[Claims] Claim 1: In freeze-drying a liquid containing a drug,
A liquid is filled into the depressions of an aluminum sheet having one or more depressions, and then freeze-dried to form a freeze-dried solid that disintegrates in water in 30 seconds or more.Then, a sheet is made to cover the aluminum sheet. A freeze-drying method characterized by covering the product with an aluminum sheet and bringing it into close contact with the aluminum sheet. 2. The freeze-drying method according to claim 1, wherein the freeze-dried solid material disintegrates with water in 30 seconds or more and has a density of 250 mg/ml or more. 3. The freeze-drying method according to claim 1, wherein the aluminum sheet having depressions is made of aluminum alone or has a multilayer structure of aluminum and a film. [Claim 4] The material of the sheet forming the lid is aluminum alone, an aluminum sheet having a multilayer structure of aluminum and a film, polyvinyl chloride, polypropylene, polyvinyl chloride/polyvinylidene chloride, polyvinyl chloride/polyvinyl chloride, The freeze-drying method according to any one of claims 1 to 3, wherein the laminate is tetrafluoroethylene or polyvinyl chloride/polyvinylidene chloride/polyethylene laminate. [Claim 5] A recessed portion of an aluminum sheet having one or more recesses is filled with a freeze-dried solid material, and a sheet serving as a lid is tightly bonded to the lower aluminum sheet by heat. Featured package.