DE3712029A1 - PRINTED SHAPED BODIES - Google Patents

Abstract

A particulate, free-flowing starch based formulation comprises (i) chemically unmodified starch or a mixture of chemically unmodified starch and no greater than 50%, by weight of the chemically unmodified starch, of another hydrophilic material, said starch or mixture being present in an amount of at least 72% by weight, based on the weight of the formulation; (ii) a texturing agent in an amount of from 0.02% to 1.0% by weight, based on the weight of the formulation; (iii) one, or a combination of both of the following components: a lubricant/release agent and a melt-flow accelerator, the one component or the combination of both components being present in an amount of from 0.4% to 5.0% by weight, based on the weight of the formulation; and (iv) water in an amount of at least 10%, based on the weight of the formulation. The compositions are used for preparing moulded bodies, e.g. capsules, for filling with pharmaceuticals and other chemicals.

Description

It is known to use compression molded molded articles made from natural materials Starch, preferably by injection molding. Such moldings are preferably produced for filling with pharmaceuticals, food, chemicals, and more, especially as pharmaceutical capsules for the dosed Administration of medication. Such containers exist usually a main part and a closing part, both parts exactly in the closed state fit and result in a tightly closed container.

The manufacture of such pressure molded containers natural strength is from the European patent application No. 84 360 940.8 (Publ. No. 1 18 240).

In industrial manufacturing, it is necessary to use the compression molded Objects, especially the very thin-walled ones pharmaceutical capsule parts with the highest precision and to manufacture at high speed. In addition, at there are absolutely no defective parts during production, for subsequent checks and interruptions in the filling machine practically turn off.

Addressing this issue of workability has proven to be surprisingly difficult. In the Manufacture of very thin-walled parts, for example with wall thicknesses of less than 0.5 mm, these are reinforced Problems.  

In particular, very good flow behavior is necessary both regarding the starting powder (free flowing starch Starting mixture) as well as during the entire injection molding process to the liquid state. The melt should flow as easily as possible to avoid high pressures and should with regard to the temperature, the mixing with the Additives and the water as homogeneous as possible demonstrate.

Furthermore, the injection molded parts are said to be a good one Demouldability and good dimensional stability about wall adhesion in the tool or deformation when Avoid expulsion.

Surprisingly, the problems can be solved if one:

1. a starch that is solid and free flowing at room temperature. Starting mixture used under the processing conditions a molding with a practically amorphous wall structure gives 2. the viscosity of the melt at 90 -240 ° C and especially 140-190 ° C between 2500 and 50 Pa · s (= Pascal · second), preferably 2000 and 50 Pa · s, is in particular 1500-50 Pa · s, and 3. the glass transition point the heated in a closed room to 140-190 ° C Mix at at least 25 ° C, preferably at least 45 ° C and in particular at about 65 ° C. These Conditions are defined with the following Composition reached.

The composition given below allows Injection molding machines in continuous 24-hour operation to drive with extensive elimination of error sources or the disadvantages mentioned above.  

In this sense, the present invention relates to a Particulate suitable for pressure molding at room temperatures and free flowing base composition, thereby marked that it contains:

• Quantity (a) chemically unmodified
  Starch 72-89.58 parts (b) at least one lubricant / release agent 0-5 parts (c) at least one accelerator
  for melt flow 0-5 parts (d) texturizing agent 0.02-1 parts (e) water 10-22 parts where
• (i) components (b) and (c) together always at least 0.4 parts and at most 5 parts and
• (ii) the sum of components (a), (b), (c), (d) and (e) always add up to 100 parts.

It has been shown that these compositions for processing under pressure, e.g. B. by Printing forms, injection molding, bubbles, extrusion and the like, own.

This basic composition can contain other components included as described below. Parts always mean parts by weight.  

That is natural with chemically unmodified starch occurring vegetable carbohydrate to understand which consists mainly of amylose and amylopectin. These Starch is made from potatoes, rice, tapioca, Maize, rye, oats, wheat and other plants are obtained. This term also includes strength with modified physical structure to understand how gelled or precooked starch and highly water soluble starch, d. H. Starch with a reduced average molecular weight. Such strength or a mixture of such starches can be found in the specified composition under pressure and elevated Process temperature into compact moldings.

The proportion of physically changed starch is preferred in natural starch not higher than 50%, preferably not higher than 20%. Natural starch is preferred.

Starch (a) is preferred in the base composition in an amount of 72-89.58 parts, preferably 75- 85 parts and preferably approx. 79-83 parts available, based on 100 parts of this composition.

The starch preferably has an amylose content of 0-70% and amylopectin from 100-30%. Is preferred Potato starch.

Suitable lubricants / release agents (b) are, for example, animal and vegetable fats, individually or in a mixture, in particular hydrogenated fats, preferably those which are solid at room temperature. These preferably have a melting point of more than 50 ° C. These fats are usually triglycerides with a proportion of C ₁₄ , C ₁₆ and C ₁₈ acids, for example C ₁₈ (approx. 65%), C ₁₆ (approx. 30%), C ₁₄ (approx. 5% ).

The amount used is preferably 0-5 parts, preferably 0-3 parts, preferably 0.6-1.2 parts based on 100 parts of the base composition.

These lubricants / release agents also act as Plasticizers and viscosity-reducing agents, so that the addition of such special agents is unnecessary.

Preferred accelerators for melt flow (c) are solid mono- and diglycerides, preferably long-chain acids, preferably of C ₁₄ -, C ₁₆ -, C ₁₈ -fatty acids, and phosphatides, in particular lecithin. Preferred addition amounts are 0-5 parts, preferably 0.1-2 parts, preferably 0.2-1 part, of such individual compounds or a mixture of such compounds based on 100 parts of the base composition.

The sum of components (b) and (c) is always at least 0.4 parts and preferably 0.8-2.0 parts based on 100 parts of the base composition.

The texturing agent (d) is titanium dioxide or silicon dioxide or a mixture of these compounds. It was found that such compounds allow free flow of the Ensure the starting material as a powder at room temperature and further during the processing process prevent bridges in the funnel and on the screw form that the feeding of the starting material on the Hinder snail. By adding these compounds the dosage is achieved from cycle to cycle takes place consistently and equally quickly.

It is therefore not necessary to granulate the starting material or otherwise pre-treat.  

The amount of the texturing agent is preferably 0.02 -1 parts based on 100 parts of the base composition. The optimum addition amount for titanium dioxide is approx. 0.4 Parts and for silicon dioxide at approx. 0.1 parts (related to 100 parts of the base composition) depending on the base composition. Of course, more titanium dioxide or Silicon dioxide can be added. However, the Excess then only as a filler and can also Adversely affect the properties of the product.

The water (e) is present in an amount of 10-22 Parts, preferably 10-20 parts, preferably 15- 19 parts based on 100 parts of the base composition, the especially for thin-walled objects preferred areas apply.

The process conditions depend primarily on the used starch, components (a) to (e) and if necessary, additionally present, mentioned below Additives.

The higher the water content, the lower the temperatures and pressures can be selected in the injection molding process. The lower the water content, the higher the pressures and temperatures to be selected. The selection of the suitable pressures and temperatures is simple and can be carried out easily by any person skilled in the art. The pressures are preferably in the range from 300 × 10 ⁵ N / m ² to 3000 × 10 ⁵ N / m ² for thick-walled objects and preferably in the range from 600 × 10 ⁵ N / m ² to 3000 × 10 ⁵ N / m ² for thin-walled objects around 900 × 10 ⁵ -1500 × 10 ⁵ N / m ² . For extrusion, depending on the water content, pressures of a few 10 ⁵ N / m ² , for. B. less than 10 × 10 ⁵ N / m ² . The working temperatures are mainly in the range of 80-240 ° C, preferably 130-210 ° C and especially 150-190 ° C.

Apparatus known per se, such as, for. B. known per se Injection molding machines or extrusion presses can be used will.

Based on the same water content, potato starch can be easier, d. H. at lower pressure and Process temperature conditions as wheat starch. The Difficulty grows in the order of potato starch, Wheat starch, corn starch, rice starch. Prefers is potato starch and wheat starch, in particular Potato starch.

In the starch-based compositions described the strength can be up to 50, preferably not more than 20% through at least one other hydrophilic material be replaced. Other usable hydrophilic materials are polymers, e.g. B. gelatin, plant proteins, such as Sunflower, soybean, cottonseed, peanut and Rapeseed proteins, blood proteins, egg proteins, acrylated Proteins, water-soluble polysaccharides, such as alginates, Carrageenans, guar gum, agar agar, gum arabic and related gums, such as ghatti gum, karaya gum and Tragacanth, pectin, water-soluble cellulose derivatives, alkyl cellulose, Hydroxyalkyl cellulose and hydroxyalkyl alkyl cellulose derivatives, e.g. B. methyl cellulose, hydroxymethyl cellulose, Hydroxyethyl cellulose, hydroxypropyl cellulose, Hydroxyethyl methyl cellulose, hydroxypropyl methyl cellulose, Hydroxybutylmethyl cellulose, cellulose esters and hydroxyalkyl cellulose esters, such as cellulose acetyl phthalate (CAP), Hydroxypropyl methyl cellulose phthalate (HPMCP), carboxyalkyl cellulose, Carboxyalkylalkyl cellulose and carboxyalkyl cellulose ester derivatives, e.g. B. carboxymethyl cellulose and their alkali metal salts, water soluble synthetic Polymers, such as polyacrylic acids and polyacrylic acid esters, Polymethacrylic acids and polymethacrylic acid esters, polyvinyl acetates, Polyvinyl alcohols, polyvinyl acetate phthalate,  (PVAP), polyvinylpyrrolidone, polycrotonic acids, phthalylated Gelatin, gelatin succinate, cross-linked gelatin, shellac, water-soluble chemical starch derivatives, cationic modified acrylates and methacrylates with, for example a tertiary or quaternary amino group, e.g. B. the Diethylaminoäthylgruppe, the quaternized if desired can be, and other similar polymers.

Preferably the starch is by no more than about 3-10% of such hydrophilic materials replaced.

Furthermore, the starch can also be replaced in whole or in part be through compounds with enteric properties, d. H. such polymers that are in aqueous media with dissolve slightly basic pH, e.g. B. Hydroxypropylmethyl cellulose phthalate (HPMCP), polyvinyl acetate phthalate (PVAP), cellulose acetyl phthalate (CAP), cationically modified Acrylates and methacrylates e.g. B. with a tertiary or quaternary amino group, such as the quaternized one Diethylaminoethyl grouping; Gelatin phthalates and / or Gelatin succinate. Gelatin is preferred.

The starch is preferably at most 20% through a derivative or a mixture of these water-soluble derivatives and / or compounds with enteric properties replaced, preferably by no more than about 3-10%.

The basic composition mentioned above can additionally Plasticizers are also preferably added in an amount 0.5-10 parts, especially 0.5-5 parts to the specified 100 parts. The starting materials with liquid additives as long as possible be mixed until fully absorbed and a solid, free-flowing mixture is created. An excess or the individual mixture grains must be stuck together be avoided. Examples of such plasticizers are  Polyalkylene oxides, such as polyethylene glycols, polypropylene glycols, Polyethylene propylene glycols; low molecular weight organic plasticizers such as glycerin, glycerin mono-, di and triacetate; Propylene glycol, sorbitol, sodium diethyl sulfosuccinate, Triethyl citrate, tributyl citrate.

The sum of the parts by weight of water and plasticizer should preferably have the specified maximum levels for water do not exceed. The sum is therefore preferably of Water and plasticizer 10-22, preferably 10-20 and preferably 15-19 parts based on 100 parts of the Basic composition.

The mixture can also be colored. Suitable dyes are, for example, known azo dyes or organic or inorganic pigments, or naturally occurring Dyes. Inorganic pigments such as that are preferred known oxides of iron or titanium in one Concentration of 0.001-10%, preferably 0.5-5%, based on the weight of all those forming the container wall Components.

As already mentioned, the invention Composition of all those carried out under pressure Use the molding process. Examples of such Shaping processes are printing forms, injection molding, bubbles or extrusion. With these shaping processes can you have a wide variety of moldings, such as containers, bottles, Foils, bags, films, packaging materials, tubes, Rods, pharmaceutical capsules and the like in the produce various known variations.

The following examples illustrate the invention:  

example 1

A composition consisting of 81 parts of natural potato starch, part of the hydrogenated triglyceride containing the fatty acids C ₁₈ : C ₁₆ : C ₁₄ in a ratio of 65: 31: 4 percent by weight, 0.7 part of lecithin, 0.3 part of titanium dioxide and 17 parts of water is mixed in a powder mixer for 10 minutes. A free flowing powder is then obtained. This powder is filled into the hopper of an injection molding machine and injected at a temperature of 180 ° C and a pressure of 1500 bar into an injection molding tool for capsule main and closure parts whose mold wall temperature is 40 ° C. After cooling and removal from the mold, a dimensionally stable capsule main or closure part is obtained which can be easily processed on a filling machine.

With this mixture, the injection molding machine can be used without continue driving 24 hours a day without machine operation must be interrupted. At the same time is the number defective capsule parts drastically reduced.

Analog results are obtained when using the following compositions according to Table 1:  

Table 1

Claims (21)

1. Suitable for pressure molding, particulate at room temperatures and free-flowing base composition, characterized in that it contains

• Quantity (a) not chemically modified
  Starch 72-89.58 parts (b) at least one lubricant /
  Release agent0-5 parts (c) at least one accelerator
  for melt flow 0-5 parts (d) texturizing agent 0.02-1 parts (e) water 10-22 parts where
• (i) components (b) and (c) together always at least 0.4 parts and at most 5 parts and
• (ii) the sum of components (a), (b), (c), (d) and (e) is always 100 parts.

2. Composition according to claim 1, characterized in that the chemically unmodified starch is a natural occurring carbohydrate, which consists of potatoes, rice, Tapioca, corn, rye, oats, wheat or others Plants obtained, gelled starch, precooked Starch and / or highly water-soluble starch. 3. Composition according to one of claims 1 or 2, characterized in that the strength in one Concentration of 75-85 parts and preferably 79 Contains -83 parts, based on 100 parts of this Composition. 4. Composition according to one of claims 1-3, characterized characterized that the starch potato starch or Represents wheat starch. 5. Composition according to one of claims 1-4, characterized characterized in that component (b) in a Concentration amount of 0-3 parts, preferably 0.6 -1.2 parts based on 100 parts of the base composition is present. 6. Composition according to one of claims 1-5, characterized characterized in that component (b) is an animal and / or vegetable fat, especially those hydrogenated Fats, preferably those that are solid at room temperature are, preferably with a melting point above 50 ° C. 7. Composition according to claim 6, characterized in that these fats are a triglyceride with a proportion of C ₁₄ -, C ₁₆ - and C ₁₈ acids, preferably C ₁₈ (approx. 65%), C ₁₆ (approx. 30%) , C ₁₄ (approx. 5%). 8. Composition according to one of claims 1-7, characterized characterized in that component (c) in a Concentration of 0.1-2 parts, preferably 0.2- 1 part based on 100 parts of the base composition, is present. 9. Composition according to one of claims 1-8, characterized in that the component is a solid mono- and / or diglyceride, preferably long-chain acids, preferably of C ₁₄ -, C ₁₆ -, C ₁₈ -fatty acids, and phosphatides, in particular lecithin , represents. 10. The composition according to any one of claims 1-9, characterized characterized in that the sum of components (b) and (c) at least 0.8-2.0 parts based on 100 parts the basic composition. 11. The composition according to any one of claims 1-10, characterized characterized in that the texturing agent (d) titanium represents dioxide and / or silicon dioxide. 12. The composition according to claim 11, characterized in that that titanium dioxide in a concentration of about 0.4 parts and silicon dioxide in a concentration of approx. 0.1 Parts present based on 100 parts of the composition is. 13. The composition according to any one of claims 1-12, characterized characterized in that the water in a concentration of 10-20 parts, preferably 15-19 parts per 100 parts of the base composition. 14. The composition according to any one of claims 1-13, characterized characterized in that the strength up to 50, conveniently not more than 20, preferably 3-10% (calculated on the strength) by another hydrophilic Material is replaced.   15. The composition according to claim 14, characterized in that the hydrophilic material from gelatin, vegetable proteins, such as sunflower, soybean, cottonseed, Peanut and rapeseed proteins, blood proteins, egg proteins, acrylated proteins, water-soluble polysaccharides, such as alginates, carrageenans, guar gum, Agar-agar, gum arabic and related gums, e.g. B. ghatti gum, karaya gum and tragacanth, pectin, water-soluble cellulose derivatives, alkyl cellulose, Hydroxyalkyl cellulose and hydroxyalkyl alkyl cellulose derivatives, such as methyl cellulose, hydroxymethyl cellulose, Hydroxyethyl cellulose, hydroxypropyl cellulose, Hydroxyethyl methyl cellulose, hydroxypropyl methyl cellulose, Hydroxybutylmethyl cellulose, cellulose esters and Hydroxyalkyl cellulose esters, such as cellulose acetyl phthalate (CAP), Hydroxypropyl methyl cellulose phthalate (HPMCP), Carboxyalkyl cellulose, carboxyalkyl alkyl cellulose and Carboxyalkyl cellulose ester derivatives such as carboxymethyl cellulose and their alkali metal salts, water soluble synthetic polymers, such as polyacrylic acids and polyacrylic acid esters, Polymethacrylic acids, and polymethacrylic acid esters, Polyvinyl acetates, polyvinyl alcohols, Polyvinyl acetate phthalates (PVAP), polyvinyl pyrrolidone, Polycrotonic acids, phthalylated gelatin, gelatin succinate, cross-linked gelatin, shellac, water-soluble chemical starch derivatives, cationically modified Acrylates and methacrylates with e.g. B. a tertiary or quaternary amino group, such as the diethylaminoethyl group, the quaternized if desired can be, and other similar polymers. 16. The composition according to any one of claims 1-15, characterized characterized in that this basic composition additionally also contains plasticizers in an amount of 0.5-10 Parts, especially 0.5-5 parts, based on the specified 100 parts preferably polyalkylene oxides,  Glycerin, glycerol mono, di and triacetate; Propylene glycol, sorbitol, sodium diethyl sulfosuccinate, Triethyl citrate, tributyl citrate. 17. The composition according to any one of claims 1-16, characterized characterized in that the sum of the parts by weight of Water and plasticizer the specified maximum levels for water does not exceed. 18. Use of a composition according to any one of the claims 1-17 for processing under pressure. 19. Use of a composition according to any one of the claims 1-17 for pressure molding, injection molding, blowing or extrusion. 20. Molded parts, in particular capsule parts, are produced from a composition according to any one of the claims 1-17. 21. Pharmaceutical capsules according to claim 20.