GB2190093A

GB2190093A - Mouldable starch compositions

Info

Publication number: GB2190093A
Application number: GB08710422A
Authority: GB
Inventors: Fritz Wittwer; Ivan Tomka
Original assignee: Warner Lambert Co LLC
Current assignee: Warner Lambert Co LLC
Priority date: 1986-05-05
Filing date: 1987-05-01
Publication date: 1987-11-11
Anticipated expiration: 2007-05-01
Also published as: DE3712029C2; GB2190093B; FR2598148A1; IT8747862A0; JPS6310644A; CH669201A5; IT1205824B; JPH07711B2; GB8710422D0; FR2598148B1; DE3712029A1; BE1000461A3

Description

GB 2 190 093 A 1

SPECIFICATION

A starch based formulation This invention relates to a starch based formulation which is particu late and free-flowing and which is useful 5 in manufacturing shaped articles by pressure forming techniques.

It is known to process starch under applied pressure and to manufacture pressure-formed moulded bodies therefrom, for example by means of injection moulding. Preferably, such moulded bodies are man ufactu red to be filled with pharmaceuticals, comestibles, chemicals and other materials, but, particularly as pharmaceutical capsules for the dosed administration of medicaments. Such capsules consist, as a rule, of a 10 body part and a cap part, which telescopically engage to provide a tightly sealed container.

The manufacture of such pressure-formed capsulesfrom natural starch is described in European Patent Application No. 84 360 940.8 (Publication. No. 118 240).

In industrial fabrication it is necessaryto manufacture pressure-formed articles, in particularvery thin-walled pharmaceutical capsule parts, with the greatest precision and at high speed. In addition, during 15 manufacture, a minimum number of defective parts should arise in orderto minimize subsequent controls and interruptions in the capsulefilling operation machine.

Mastering these processing problems has proved to be surprisingly difficult. With the manufacture of very thin-walled parts, forexample with wall thicknesses of lessthan 0.5 mm, the problems intensify.

In particular a very good flow behaviourof the composition to be moulded is necessary, both with 20 referenceto the starting powder (freelyflowing starch starting mixture), aswell as during the injection-moulding process uptothe momentatwhich the moulding composition reaches thefluid state.

The molten mass should, to avoid high pressures, flow as easily as possible and should, with regard tothe temperature, and the intermixing with additives and water, show as homogenous a distribution as possible.

Furthermore, the injection-moulded parts should be easily removed from the mould, as well as having 25 good dimensional stability, in orderto avoid adherenceto thewall in thetool ordeformation on ejection.

It has, surprisingly, been found thatthe problems can be solved, if the following requirements are satisfied:

1. a starch starting mixture which is particulate and free-flowing at room temperature is used, which results, underthe processing conditions employed, in a moulded article with a practically amorphous wall 30 structure; 2. the viscosity of the molten mass at 90 - 240'C, particularly 140 - 190'C lies between 2500 and 50 Pas(= Pascal x second), preferably between 2000 and 50 Pa s, and more preferably between 1500 - 50 Pa s; and 3. the glass transition point of the mixture heated in a closed space up to 140 - 1190'C should beat least 25'C, preferable at least 450C and most preferably about 65'C. 35 According to the present invention there is provided a particulate, free- flowing starch based formulation comprising (i) chemically unmodified starch ora mixture of chemically unmodified starch and no greaterthan 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 theformulation; 40 (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 orthe combination of both components being present in an amount of from 0.40% to 5.0% by weight, based on the weight of the formulation; and 45 (M water in an amount of at least 10%, based on the weight of the form u lation. This formulation enables the requirements specified above to be satisfied.

The formulation specified above permits injection-moulding machines to be driven in continuous 24-hour operation, with minimal errors and without the disadvantages mentioned above.

It has been found that these formulations are suitable for use in processing under applied pressureJor 50 example pressure-moulding, injection-moulding, blow-moulding, extrusion etc.

The basic formulation can include further components, as is described further below.

The chemically unmodified starch employed in this invention maybe a vegetable carbohydrate, which mainlyconsists of arnylose and arnylopectin. This vegetable starch may be obtained, forexample,from potatoes, rice,tapioca, corn, rye, oats, wheatand other plants. Alternatively, or in addition,the chemically 55 unmodified starch may be a starch which has a physically modified structure, such as gelatinized or pre-cooked starch and highly water-soluble starch. Such a starch or a mixture of such starches can be processed in the specified formulation under pressure and raised temperatureto form compact moulded bodies.

Preferablythe proportion of physically altered starch to natural starch is not higherthan 50%, preferably 60 not higherthan 20%. Most preferred is natural starch.

The starch is present in the basic somposition in a quantity no lessthan about72% byweight based onthe weight of theformulation, preferably no greaterthan 89%to 58%, more preferably in the range of from 75% to 85% byweight based on theweight of theformulation and most preferably between 79% to 83% byweight based on the weight of theformulation. 65 2 GB 2 190 093 A 2 The starch preferably has an arnylose contentof from 0-70% and arnylopectin of 100 -30%. Mostpreferred is potato starch.

Suitable asthe lubricant/release agent are animal and vegetablefats, individually or in a mixture, in particular such fats which are hydrated and, preferably those which aresolid at room temperature. Preferably they havea melting pointof over50'C. Thesefats are, asa rule, triglycerides with a proportion OfC14-, C16-and 5 C113-acids, for example C18 (around 65%), C16 (around 30%), C14 (around 5%).

Thequantityof lubricant/release agentemployed is preferablyO-5% more preferablyO-3% and most preferably 0.8 - 1.2% byweight based on theweightof theformulation.

These iubricant/release agents act simultaneously as softening agents, and viscosity depressants so that the addition of such special agents is unnecessary. 10 The melt-flow accelerator is preferably a mono-or a diglyceride, more preferably a long-chained acid preferably OfC14-, C16-, C18-fatty acids and phosphatides, in particular lecithin. The melt-flow accelerator is preferably employed in an amount of from 0 - 5%, preferably 0.1 - 2%, more preferably 0.2 - 1 % byweight based on the weight of the formulation.

The sum of the amounts of the lubricant/releasing agent and the melt-flow accelerator should amountto at 15 least 0.4%, and preferably from 1 - 2.2% byweight based on the weight of the formulation.

The texturing agent is preferably titanium dioxide or silicondioxide or a mixture of these compounds. It has been found that such compounds guarantee a free fowing of the starting material as a powder at room temperature and further preveritthe formation of bridges in the funnel and atthe screw during processing, which hinderthefeed of the starting material onto the screw. Through the addition of the texturing agent,the 20 dosing takes place constantly and evenly, and equallyfastfrom cycle to cycle.

It is thus not necessary to granulate or otherwise pretreatthe starting material.

The quantity of the texturing agent should be 0.02 - 1 % by weight based on the weight of theformulation.

Fortitanium dioxide, the optimum addition quantity lies at about 0.25%, and for silicon dioxide, around 0.1 % byweight based on the weight of the formulation. Naturally more titanium oxide or silicon oxide can also be 25 added, though the excess then acts simply as a filler and may negatively influence the properties of the product.

The water is present in a quantity of 10 - 22%, preferably 10 - 20%, more preferably 15 - 19% by weight based on the weight of the formulation. Forthin-walled articles the preferred ranges are applicable.

The process conditions depend principally on the starch used; the other components of the formulation 30 and the additives mentioned further below, which may be included if necessary.

The higherthe water content, the loliverthe temperatures and pressures which can be chosen in the injection-moulding process. The lower the water content, the higherthe pressures and temperatures to be chosen. The selection of suitable pressures and temperatures is simple and can be carried out easily bythe expert. The pressures lie, forthicker-walled articles, in the range of from 300 X 1 05N1M2 to 3000 x 105 N/M2 35 and, forthinner-wal led articles, in the range 600 = 105N1M2 to 3000 x 105NIM2, preferably at about 900 x 105 - 1500 x 105 N/M2. For extrusion,. pressures of afew bars may be used, forexample lessthan 10 bars, depending on the water content. The working temperatures lie predominantly in the range of from 80 -240'C, preferably 130-210'C and most preferably at 150-1900C.

Devices known perse, for example injection moulding machines known perse, can be used. 40 With formulations having the same water content, potato starch can be processed more easily, i.e.with lowerpressure and temperature conditions, than wheat starch. The degree of difficulty increases intheorder potato starch, wheat starch, corn starch, rice starch. Preferred is potato starch and wheatstarch, in particular potato starch.

Inthe above-mentioned starch formulations, upto 50% of the starch can be replaced by one or moreofthe 45 other hydrophilic materials for example, gelatin, vegetable proteins such as: sunflower protein,soybean proteins, cotton seed proteins, peanut proteins, rapeseed proteins, blood proteins, egg proteins, acrylated proteins; water-soluble polysaccharides such as: alginates, carrageenans, guargum, agar-agar, gum arabic and related gums (gum ghatti, gum karaya, gumtragacanth), pectin; water- soluble derivatives of cellulose:

alkylcelluloses hydroxyalkylcel 1 u loses and hydroxyal kylalkylcel lu loses, such as: methylcell u lose, 50 hydroxymethylcellulose, hydroxyethylcel 1 u lose, hydroxypropylcellulose, hyd roxyethyl methyl cell u lose, hydroxpropyl methylcel lu lose, hydroxybutyimethylcellulose, celluloseesters and hydroxyalkylcelluloseesters such as: celluloseacetylphthalate (CAP), hyd roxypropyl methylcel 1 u losephtha late (HPC1VIP); carboxyalkylcelluloses, carboxyalkylalkylcel lu loses, carboxyalkylceliuloseesters such as: carboxymethylcellulose and their alkli metal salts; water-soluble 55 synthetic polymers such as: polyacrylic acids and polyacrylic acid esters, polymethacrylic acids and polymethacrylic acid esters, polyvinylacetates, polyvinylalcohols, polyvinylacetatephthalates (PVAP), polyvinylpyrrolidone, polycrotonic acids; suitable are also phthalated gelatin, gelatin succinate, crosslinked gelatin, shellac, water soluble chemical derivatives of starch, cationically modified acrylates and methacrylates possessing, for example, a tertiary or quaternary amino group, such as the diethylaminoethyl 60 group, which may be quaternized if desired; and othersimilar polymers.

Preferablythe starch is replaced by not more than 3 - 10% of one of these hydrophilic materials.

To the above-mentioned basic formulations can be added a softening agent in a quantity of, preferably, 0.5 - 10% by weight based on the weight of the formulation. In addition, the starting materials may be mixed with liquid additives until they are completely absorbed and firm pourable mixture arises. An excess or a sticking 65 3 GB 2 190 093 A 3 together of the individual mix grains must be avoided. Such softening agents are, for example, polyalkylene oxides, such as polyethyleneglycols, polypropyleneglycols, polyethylenepropyleneglycols; low-molecular organic softening agents I ike glycerine, glycerin mono-,di- and triacetate; propyleneglycol,sorbitol,sodiu m diethyl sulfosuccin ate, triethylcitrate,tributyleitrate.

The sum of the weight parts of water and softening agent should preferably not exceed the specified 5 maximum contents for water. Preferably, therefore, the sum of water and softening agents amounts to 10 22%, preferably 10 -20%, most preferably 15-19% by weight based on the weight of the formulation.

The mixture can also be dyed. Suitable dyestuffs are, for example, known azo dyes or organic or inorganic pigments, or naturally occurring dyestuffs. Preferred are inorganic pigments, such as iron or titanium oxides in amounts of from 0.001 - 10%, preferably 0.5-5%, by weight based on the weight of the formulation. 10 As mentioned above, the formulation of the present invention can be used in a I I types of molding techniques under applied pressures such as pressure-molding, injection-molding, blow-molding or extrusion and it is possible to produce such articles as containers, bottles, sheets, sacks, films, packaging materials, tubes, rods, pharmaceutical capsules etc, in all the numerous variations known.

The present invention wi I I now be il I ustrated by reference to the following Examples: 15 Example 1

Acomposition consisting of 81 parts of natural potato starch, one part of hydrated triglyceride containing thefatty acids C18:C16:C14in a ratio of 65:31:4 weight percent, 0.7 parts lecithin,0.3 partstitanium dioxideand 17 partswater is mixed in a powder mixerfor 10 minutes. Thereafter a freely flowing powderis obtained.This 20 powder isfilled intothefunnel of an injection-moulding machine and, at atemperature of 1180'C and a pressure of 1500 bar, injected into an injection moulding toolforcapsule main and sealing partswhose mouldwall temperature lies at40'C. After cooling and ejecting from the mould a dimensionally stable capsule main orsealing part is obtained,which can easily be processed on afilling machine.

With this mixturethe injection moulding machine can easily be driven in 24-hour operation without 25 interruptions to the machine ordetectable defectstothe capsule parts being produced.

Analogous resultswere obtained using different compositions, the details of which are setforth in Table 1:

No. Starch Componentb) Componentc) Componentd) Water Others Type % Type % Type % Type % % Type % 30 1 Potato 75,00 hydrated vege- 1.25 Lecithin 1.5 Ti02 0.25 22.0 tablefat

2 Potato 80.00 hydrated veg e- 1.0 Lecithin 0.9 Ti02 0.1 18.0 table fat 35

3 Potato 88.6 hydrated vege- '0.8 Lecithin 0.5 SiO, 0.1 10.0 table fat

4 Wheat 78.0 hydrated vege- - Monoglycerid, 5.0 Si02 3.04 19.0 dyestuff 0. 96 tablefat C18

Wheat 79.0 hydrated veg e- 2.05 TiO2/ 0.95 18.0 - - tablefat Si02 1:1 40 6 Wheat 85.0 hydrated 480 Ti02 0.20 12.0 - - animal fat 7 Maize 75.0 hydrated 4.80 Monoglycerid, 0.2 Ti02 0.15 17.0 pre-cooked 2. 85 animal fat C18 starch 8 Maize 78.0 hydrated 3.0 Monoglycerid 1.0 Ti02 0.05 14.0 pre-cooked 3.95 45 animalfat C18 starch 9 Rice 79.0 Monoglycerid 2.0 Si02 1.0 17.5 dyestuff 0.5 C18 Rice 80.25 hydrated 0.9 Diglyceride, 0.6 Si02 0.25 15.0 Glycerin 3 animal fat C18,C16 11 Tapioca 75.2 hydrated 0.9 Diglyceride, 0.6 Si02 0.3 21.0 HM12CP 2 50 animalfat C18, C16 12 Potato 73.96 hydrated 2.0 Diglyceride, 2.0 Si02 0.04 17.0 PEG 1000 5 animal fat C18,C16 13 Potato 75.25 hydrated 1.5 Diglyceride, 1.0 Ti02 0.25 18.0 PEG 4000 4 animal fat C18,C16 55 14 Potato 75.25 vegetablefat 1.5 Lecithin 1.0 TiO, 0.25 18.0 Sorbitol 4 Wheat 60.00 vegetablefat 1.5 Lecithin 1.2 Ti02 0.25 17.0 Polyacrylic 20. 05 acid

Claims

CLAIMS 60

1. A particulate,free-flowing starch based formulation comprising 4 GB 2 190 093 A 4 (i) chemically unmodified starch ora mixture of chemically unmodified starch and no greaterthan 50%, by weightof the chemically unmodified starch, of another hydrophilic material,said starch or mixture being presentin an amountof atleast72% byweight, based on theweightof theformulation; (H) atexturing agent in an amountof from 0.02%to 1.0% byweight, based on theweightof theformulation; (iii) one, ora combination of both,of thefollowing components: a 1 u bricant/rel ease agent and a melt-flow 5 accelerator,the one componentorthe combination of both components being present in an amountoffrom 0.40/6to 5.0% byweight, based on the weight of the formulation; and (M waterin an amountof atleast 10%, based ontheweightof theformulation.

2. Aformulation according to Claim 1, wherein the chemically unmodified starch is a naturally occurring carbohydrate, obtained from one or more of the following sources: potatoes, rice, tapioca, corn, rye, oats, 10 wheat or other plants, gelatinized starch, pre-cooked starch and highlywater-soluble starch.

3. A formulation according to Claim 1 or 2, wherein the starch is potato starch or wheatstarch.

4. A formulation according to Claim 1, 2 or 3 wherein the starch is present in an amount no greaterthan about 90% by weight, based on the weight of the formulation.

5. Aformulation according to Claim 4, wherein the starch is present in an amount of from 75 to 851/6 by 15 weight, based on the weight of the formulation.

6. A formulation according to Claim 5, wherein the starch is present in an amount of from 79 to 83% by weight, based on the weight of the formulation.

7. A formulation according to any preceding claim wherein the lu bricant/release agent, when present, is present in an amount no greaterthan 3% by weight, based on the weight of theformulation. 20

8. A formulation according to any preceding claim, wherein the lu bricant/release agent is present in an amount of from 0.6% to 1.2% by weight, based on the weight of the formulation.

9. Aformulation according to any preceding claim, wherein the lubricant/release agent is an animal and/or vegetable fat.

10. Aformulation according to Claim 9, wherein the lubricant/release agent is a hydrated animal or 25 vegetablefat.

11. A formulation according to Claim 9 or 10, wherein the animal or vegetable fat is solid at room temperature.

12. Aformulation according to Claim 9, 10 or 11, wherein the animal orvegetable fat has a melting point above 50T. 30

13. Aformulation according to anyone of Claims 9 to 12, wherein the animal or vegetable fat is a triglyceride having a proportion Of C14-, C16, C18 fatty acids.

14. A formulation according to Claim 13, wherein the proportion of each fatty acid is as follows:

C18 - approximately 65%; C16 - approximately 30%; and 35 C14approximately 5%.

15. A formulation according to any preceding claim wherein the melt-flow accelerator is present in an amount of from 0.1 to 2% by weight, based on the weight of theformulation.

16. Aformulation to any preceding claim, wherein the melt-flow accelerator is present in an amountof from 0.2 to 1 %by weight, based on the weight of the formulation. 40

17. A formulation according to any preceding claim wherein the meittYlow accelerator is a solid mono andlordiglyceride.

18. A formulation according to any preceding claim, wherein the melt flowaccelerator is along chained fatty acid, for example a C14-, C16- or C18fatty acid or a phosphatide.

19. Aformulation according to any preceding claim, wherein the melt-flow accelerator is lecithin. 45

20. Aformulation according to any preceding claim, wherein the combined amount of the lubricant/release agent and the melt-flow accelerator is in the range of from 1 to 2.2% by weight, based on the weight of the formulation.

21. Aformulation according to any preceding claim, wherein the texturing agent is titanium oxide and/or silicon dioxide. 50

22. Aformulation according to Claim 21, wherein the titanium dioxide is present in an amount of about 0.25% and the silicon dioxide in an amount of about 0.1 %,both percentages being by weight, based on the weight of the formulation.

23. Aformulation according to any preceding claim, wherein the water is present in an amount no greater than 22% byweight based on the weight of the formulation. 55

24. Aformulation according to any preceding claim, wherein the water is present in an amount of from 10 to 20% byweight, based on the weight of the formulation.

25. A formulation according to any preceding claim, wherein the water is present in an amount of from 15 to 19% byweight, based on the weight of the formulation.

26. Aformulation according to any preceding claim, wherein component (i) of the formulation isthe 60 mixture of a chemically unmodified starch and another hydrophilic material in which the other hydrophilic material is present in an amount no greater than 20% byweight of the chemically unmodified starch.

27. A formulation according to Claim 26, wherein the other hydrophilic material is present in an amount of from 3 to 10% by weight of the chemically unmodified starch.

28. Aformulation according to any preceding claim wherein the hydrophilic material is selected from: 65 GB 2 190 093 A 5 gelatin, vegetable proteins such as: sunflower protein, soybean proteins, cotton seed proteins, peanut proteins, rape seed proteins, blood proteins, egg proteins, acrylated proteins; water-soluble polysaccharides such as: alginates, carrageenans, guar gum, agar-agar, gum arabic and related gums (gum ghatti, gum karaya, gum tragacanth), pectin; water-soluble derivatives of cellulose: alkylcelluloses hydroxyalkylcelluloses and hydroxyalkylaikycelluloses, such as: methylcellulose, hydroxymethycellulose, 5 hydroxyethylcel 1 u lose, hydroxypropylcel 1 u lose, hydroxyethyimethylcellu lose, hyd rexpropyl methylcell u lose, hyd roxybutyl methyl cell u lose, cellulose.esters and hydroxyalkylcellulose esters such as: cell u loseacetyl phthalate (CAP), hyd roxypropyl methyl cell u 1 osephtha late (HPC1VIP); carboxyal kylcel 1 u loses, carboxyalkylalkylcel lu loses, carboxyalkylcelluloseesters such as:

carboxymethylcellulose and their alkli metal salts; water-soluble synthetic polymers such as: polyacrylic 10 acids and polyacrylic acid esters, polymethacrylic acids and polymethacrylic acid esters, po lyvi nyl acetates, polyvinylalcohols, polyvinylacetatephthalates WVAP), polyvinylpyrrolidone, polycrotonic acids; suitable are also phthalated gelatin, gelatin succinate, crosslinked gelatin, shellac, watersoluble chemical derivatives of starch, cationically modified acrylates and methacrylates possessing, forexample, a tertiary orquaternary amino group, such asthe diethylaminoethyl group, which may be quaternized if desired; and othersimilar 15 polymers.

29. Aformulation according to any preceding claim, further comprising a softening agent in an amount of from 0.5 to 10% by weight, based on the weight of theformulation.

30. Aformulation according to Claim 29, wherein the softening agent is present in an amount of from 0.5 formulation. 20

31. Aformulation according to Claim 29 to 30, wherein the softening agent is chosen from polyalkylene oxides, glycerin, glycerin mono-, di-, and triacetate; propylene glycol, sorbitol, sodi u m -d iethyl su Ifosu cci n ate, triethylcitrate, tri butylcitrate.

32. Aformulation according to any preceding claim, wherein the total weight percentage of the water and softening agent does not exceed 22% by weight based on the weight of the formulation. 25

33. The use of a formulation according to any preceding claim in processing under applied pressure.

34. The use of a formulation according to anyone of Claims 1 to 32 in pressure moulding, injection moulding, blow moulding or extrusion.

35. An article made under applied pressure from a formulation as claimed in anyone of Claims 1 to 32.

36. An article according to Claim 35 being a pharmaceutical capsule. 30 Printed for Her Majesty's Stationery Office by Croydon Printing Company (L1 K) Ltd,9187, D8991685. Published by The Patent Office, 25 Southampton Buildings, London WC2A l AY, from which copies maybe obtained.

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