FR2775979A1 - Polyvinyl alcohol film forming compositions - Google Patents

Abstract

A new film forming composition contains polyvinyl alcohol and a setting system.- DETAILED DESCRIPTION - INDEPENDENT CLAIMS are included for (i) containers for unit dosage forms for agrochemicals, seeds, herbs, foodstuffs, dyestuffs, pharmaceuticals or flavouring agents produced from the novel composition; (ii) caplets encapsulated in the novel composition; (iii) aqueous solns. of the novel composition for manufacturing capsules; (iv) use of aqueous gelatin solutions of the novel composition for manufacturing hard capsules in a dip moulding process

Description

 The present invention relates to polyvinyl alcohol (PVA) compositions for use in products such as pharmaceutical, veterinary, food, cosmetic or the like, for wrapping food, aspic or jelly products, preferably for formulations pre-dosed as soft or hard capsules. Compared to hard gelatin capsules (HGC), PVA capsule films have extremely low water vapor permeability and much lower water content.

 According to a second embodiment, the present invention relates to the use of film compositions for the manufacture of hard capsules by conventional dip molding methods normally used for the manufacture of conventional hard gelatin capsules.

 For the industrial manufacture of pharmaceutical capsules, gelatin is particularly preferred for its gelling, film-forming and surface-active properties.

The manufacture of hard gelatin capsules by immersion molding processes fully utilize these gelling and film forming abilities. These capsules are made by dipping molding pins into a hot gelatin solution, removing the pins from the gelatin solution, allowing the gelatin solution retained by the pins to cool, drying and separating the resulting shells. some pins. Taking the solution on the dip molding pins is the critical step in achieving a uniform thickness of the capsule shell.

 A primary limitation of the use of hard gelatin capsules is the exchange of moisture between the capsules and their liner. Gelatin naturally has hygroscopic properties and hard gelatin capsules usually contain about 10 to 16% by weight of water. This water content is a function of the relative humidity (RH) of the environment. When the capsules are filled and stored in a vapor-tight container, the moisture will be redistributed between the various constituents until a uniform relative humidity is reached in the vapor phase of the shell of the capsule, the filling and the environment.

 Another disadvantage of gelatin films and an undesirable limitation of its use, is its high permeability to water vapor, which leads to a high speed of water vapor transport through the gelatin shell of the capsules when the filling is hygroscopic or when the capsules are stored in a moist environment. Experimental test results show that at 22 ° C, for a relative humidity difference of 50% between the two sides of a 100 μm thick gelatin film in a 24 hour period, a permeation at 2 times the weight of the gelatin film per 24 hours, therefore, when the capsules are exposed to an open environment, the liner will absorb moisture from the environment through permeation through the shell of the capsule until we reach equilibrium.

 The moisture absorption of a capsule liner by moisture exchange or permeation through the shell of the capsule can adversely affect the properties of the liner.

The powder packings may agglomerate or, more seriously, the packings may undergo chemical degradation, for example by hydrolysis. In general, it is necessary to store pharmaceutical gelatin capsules in a dry environment.

 The affinity of the capsules and their fillings for water and the exchange of moisture between the capsules and their filling can be determined by the sorption-desorption isotherms. For gelatin, this is well described in the literature, for example in K. Ito et al., Chem. Pharm. Bull. 17 (3) 1969, 1134-37. M.J. Kontny & al., Int. J. Pharm. 54, 1989, 79-85 discloses a mathematical model for predicting the final relative water vapor pressure in a closed system for a multicomponent mixture of solids if the aqueous content of each of the constituents is known. From the relative final pressure and the sorption-desorption isotherms, it is then possible to estimate the amount of redistribution of moisture through the vapor phase between the various constituents.

 There are few published studies on the permeability of hard gelatine capsules for water vapor. W. A. Strickland et al., J. Pharm. Sci., 51 (10) 1962, 1002-5, discloses the diffusion of water vapor through the hard gelatin capsules and concludes that the gelatin capsules have only poor protection to a microscopic screw liner. with respect to atmospheric water vapor. To overcome this disadvantage, it has been suggested in WO 97/04755 to incorporate a polyol additive into the gelatin film composition or hard gelatin capsules.

 It is well known that PVA film compositions exhibit extremely low water vapor permeability, the lowest of known water-soluble film-forming products and it is widely used for coating compositions, particularly for pharmaceutical formulations. as tablets as described in WO 96/01874.

EP-A-0 180 287 discloses the use of PVA in combination with cellulose ethers in hard capsule film compositions. In these compositions, the setting of the immersion solution is obtained by thermal gelation of cellulose ether such as hydroxypropyl methylcellulose (HPMC). However, to obtain acceptable setting properties of the film-forming composition, the content of
HPMC must be extremely high, and even higher than the PVA content. Therefore, the advantages of PVA properties will be significantly lowered in these compositions.

 The present invention relates to film-forming compositions consisting of polyvinyl alcohol and setting system.

 According to one embodiment, the setting system consists of hydrocolloids and cations.

 According to another embodiment, the setting system optionally contains sequestering agents.

 According to yet another embodiment, the polyvinyl alcohol is present in a proportion of 90 to 97% by weight, the water content is 2 to 7% by weight and the hydrocolloids are present in a proportion of 0.01 to 10%. preferably 0.05 to 5% by weight, and the cations in an amount of 0.001 to 5%, preferably 0.01 to 3% by weight.

 According to yet another embodiment, the setting system optionally contains sequestering agents in a proportion of 0.01 to 5%, preferably 0.01 to 3% by weight of the composition.

 According to one embodiment of the invention, the hydrocollolds of the setting system are chosen from polysaccharides, and more particularly, the hydrocolloids of the setting system are chosen from alginates, agar gum, guar gum, carob bean gum (carob), carrageenan, tara gum, gum arabic, ghatti gum, Khaya grandifolia gum, tragacanth gum, karaya gum, pectin, arabian (arabic) ), xanthan, gellan, starch, Konjac mannan, galactomannan or funorane.

 According to another embodiment, the hydrocolloids of the setting system are chosen from xanthan, acetan, gellan, wélane, rhamsane, furcellerane, succinoglycan, scleroglycan, schizophyllane, tamarind gum, curdlan, pullulan or dextran, gellan gum or kappa-carrageenan.

 According to yet another embodiment, the possible sequestering agents CLI mixtures of sequestering agents of the setting system are chosen from ethylenediamine tetraacetic acid, acetic acid, boric acid, citric acid, acid and the like. edetic, gluconic acid, lactic acid, phosphoric acid, tartaric acid and their salts, metaphosphates, dihydroxyethylglycine, lecithin or betacyclodextrin, or the salts of the acids mentioned.

 The film-forming compositions according to the invention may also contain plasticizers in a proportion of approximately 0 to 40% relative to the weight of PVA.

 According to one embodiment of the invention, the plasticizer or the mixture of plasticizers is chosen from polyethylene glycol, glycerol, sorbitol, sucrose, corn syrup, fructose, dioctylsulphosuccinate sodium, triethyl citrate, tributyl citrate, 1,2-propylene glycol , glycerol mono-, di- or triacetate, or natural gums.

 The film-forming compositions according to the invention may also contain coloring agents in a proportion of approximately 0 to 10%, expressed relative to the weight of the PVA.

According to one embodiment of the invention, the coloring agent or the mixture of coloring agents is chosen from azo, quinophthalone, triphenylmethane, xanthene or indigo dyes, iron oxides or hydroxides, titanium dioxide or dyes. natural, and more particularly the coloring agent or mixture of coloring agents is chosen from patent blue V, brilliant green acid BS, red 2G, azorubine, culvert 4R, maroon, red D + C 33, the red
D + C 22, red D + C 26, red D + C 28, yellow D + C 10, yellow 2 G, yellow
FD + C 5, yellow FD + C 6, red FD + C 3, red FD + C 40, blue FD + C 1, blue FD + C 2, green FD + C 3 or glossy black BN, carbon black, iron oxide black, iron oxide red, iron oxide yellow, titanium dioxide, riboflavin, carotenes, anthocyanins, curcumin, cochineal extract, chlorophyllin, xanthaxanthin, caramel or betanin.

 The present invention relates to containers for unit dosage forms for agronomic chemicals, seeds, herbs, foodstuffs, colorants, pharmaceuticals or flavoring agents obtained from the compositions presented, said containers consisting of a pharmaceutical capsule possibly comprising a coating. .

According to one embodiment, the coating is chosen from cellulose acetate phthalate, polyvinyl phthalate acetate, methacrylic acid gelatins, hypromellose phthalate, hydroxypropyl methylcellulose phthalate, hydroxyalkyl methylcellulose phthalate or mixtures thereof.
the subject of the present invention is also the film-forming compositions as described above.

 The capsules according to the invention are preferably formed of half-capsules sealed with one or more layers of compositions as described above, and preferably sealed by a liquid melting operation.

 The invention also relates to aqueous solutions of compositions as described above, for the manufacture of capsules, these aqueous solutions preferably containing polyvinyl alcohol in a proportion of 10 to 60%, preferably 20 to 40 % by weight, hydrocolloids in a proportion of 0.01 to 5%, preferably 0.03 to 1% by weight, and cations in an amount of 0.001 to 3%, preferably 0.01 to 1% by weight of the aqueous solution, and optionally containing sequestering agents in an amount of 0.001 to 5%, preferably 0.01 to 1% by weight of the aqueous solution.

 The invention further relates to the use of aqueous PVA solutions, for the manufacture of hard capsules by an immersion molding process and the manufacture of hard capsules from aqueous polyvinyl alcohol solutions, by a molding method. immersion using equipment and manufacturing parameters of conventional hard gelatin capsules.

 The object of the present invention is therefore to obtain polyvinyl alcohol (PVA) compositions for use in pharmaceutical, veterinary, food, cosmetic or other products, such as films for packaging foods, aspics or jellies, preferably for pre-dosed formulations such as soft and hard gelatin capsules and wherein the PVA composition has sufficient curing capacity in aqueous solution.

 It has surprisingly been found that the addition of a very small amount of a setting system, preferably consisting of hydrocollolds, more preferably polysaccharides, greatly improves the curing ability of PVA solutions for the manufacture of capsules. Hard PVA by conventional immersion molding methods.

The present invention therefore aims to obtain compositions of
PVA / curing system, preferably for films intended for pharmaceutical, veterinary, food, cosmetic or other products, particularly preferred for the preparation of capsules for premixed formulations, in particular hard capsules.

 The addition of a setting system, preferably based on polysaccharides, to PVA solutions allows the adaptation of the particular and desired gelling properties to the production of hard PVA capsules by conventional immersion methods. In making these capsules, it is extremely important that the film-forming PVA solution remaining on the molding pins after immersion is prevented from flowing out of the pins. Otherwise, the films obtained do not have the desired uniform thickness.

 Therefore, hard PVA capsules can be made with the same equipment used for the manufacture of conventional hard gelatin capsules in the same range of the same manufacturing conditions. In addition, the capsules obtained from the compositions of the present invention have the same dimensional specifications and allow the use of the same existing filling facilities and do not require special and novel equipment for filling operations.

 The PVA capsules obtained from the film-forming compositions of the present invention consist mainly of PVA and therefore have the properties of pure PVA as very low water vapor permeability, low hygroscopicity, excellent perforation behavior in a low relative humidity and, in addition, the benefits of the gelatin capsules that have been cited.

 The concentration of PVA in the molding solution is between 10 and 60%, preferably between 20 and 40% by weight.

 The setting system consists of a hydrocolloid or hydrocolloid mixtures and may additionally contain cations and / or sequestering agents.

 Colloids or suitable mixtures producing synergistic properties may be chosen from natural marine plants, natural seed gums, exudates from natural plants, natural fruit extracts, bio-synthetic gums, gelatins, and starches treated by the same route. bio-synthetic or cellulosic products, preferably polysaccharides.

 The preferred polysaccharides are alginates, agar gum, guar gum from carob bean gum (carob), carrageenan tara gum, gum arabic, ghatti gum, Khaya grandifolia gum, tragacanth gum, karaya gum, pectin, arabian (araban), xanthan, gellan, starch, Konjac mannan, galactomannan, funorane, and other exocellular polysaccharides. Exocellular polysaccharides are preferably used.

 Preferred exocellular polysaccharides are xanthan, acetan, gellan, wielane, rhamsane, furcellerane, succinoglycan, scleroglycan, schizophyllan, tamarind gum, curdlan, pullulan and dextran.

 The preferred hydrocolloids are kappa-carrageenan or gellan gum. or combinations such as xanthan and locust bean gum or xanthan with Konjac mannan.

 Of the above-mentioned setting systems, kappa-carrageenin systems with a cation and gellan gum with a cation are particularly preferred. They give high strength gels at low concentration and have excellent compatibility with PVA.

The amount of hydrocolloid is preferably in the range of 0.01 to 5% by weight and most preferably 0.03 to 1.0% in the aqueous solution of
PVA.

 Preferably, the cations are selected from K +, Na + Li +, NH4 +, Ca ++ or, for kappa-carrageenin, K +, NH4 + or Ca ++ are preferred. The amount of cation is preferably from 0.001 to 3%, in particular from 0.01 to 1% by weight in the aqueous PVA solution.

The preferred sequestering agents are ethylenediamine tetraacetic acid,
Acetic acid, Boric acid, Citric acid, Edetic acid, Gluconic acid,
Lactic acid, phosphoric acid, tartaric acid or their salts, methaphosphates, dihydroxyethylglycine, lecithin or beta-cyclodextrin and combinations thereof. Particularly preferred is ethylene diamine tetraacetic acid or its salts or citric acid and its salts. The amount is preferably from 0.001 to 3%, in particular from 0.01 to 1% by weight of the immersion solution.

 In addition, it is possible to incorporate a small amount of an antifoaming agent into the PVA solution to prevent the formation of bubbles that can lead to visual imperfections of the capsules.

 The PVA capsules obtained from the solutions as described will therefore contain by weight 2 to 7% water, 90 to 97% PVA, 0.01 to 100%, preferably 0.05 to 5%. hydrocolloids, 0.001 to 5%, preferably 0.01 to 3% of cations depending on the hydrocolloids used and, where appropriate, 0.001 to 5%, preferably 0.01 to 3% of sequestering agents.

The PVA compositions of the present invention may contain, in another aspect, additional pharmaceutically or food-acceptable coloring agents at 0 to 10% based on the weight of PVA. The coloring agents may be chosen from azo, quinophthalone, triphenylmethane, xanthene or indigoid dyes, iron oxides or hydroxides, titanium dioxide or natural dyes, or mixtures thereof. As examples, mention may be made of patented blue V, brilliant green acid BS, red 2G, azorubine, culvert 4R,
Amaranth, red D + C 33, red D + C 22, red D + C 26, red D + C 28, yellow D + C 10, yellow 2 G, yellow FD + C 5 , yellow FD + C 6, red FD + C 3, red FD + C 40, blue FD + C blue FD + C 2, green FD + C 3, glossy black
BN, carbon black, iron oxide black, iron oxide red, iron oxide yellow, titanium dioxide, riboflavin, carotenes, anthocyanins, curcumin, cochineal extract, chlorophyllin, xanthaxanthin, caramel or betanin.

 The PVA capsules of the present invention may be coated with a suitable coating agent such as cellulose acetate phthalate, polyvinyl acetate phthalate, methacrylic acid gelatin, hypromellose phthalate, hydroxypropylmethylcellulose phthalate, hydroxyalkylmethylcellulose phthalate or mixtures thereof, to obtain, for example, enteric properties.

 The PVA capsules of the present invention can be used for the manufacture of containers to obtain unit dosage forms, for example in the agrochemical field of seeds, herbs, food products, coloring products, pharmaceuticals, flavoring agents and the like.

 The PVA compositions according to the invention are of interest for the encapsulation of grains in a capsule, in particular in a form protected from manipulation. The encapsulation of grains in a capsule is preferably effected by cold crimping together the capsule elements, which are filled with grains, which comprises the steps of taking empty capsule elements, filling at least one of the capsules. said capsule elements with one or more grains, assembling said capsule elements and treating the combined capsule elements by cold crimping.

 The PVA capsules of the present invention are also useful for encapsulating and sealing the two half-capsules in a process wherein one or more layers of a bonding agent are applied to the junction of the cap body, or by a melting operation in which the capsules filled are wet with a PVA solvent which enters the space where the cap covers the body and then dried.

 Capsules or films having the PVA composition of the present invention can be made using conventional machines by conventional methods such as extrusion molding, injection molding, casting or dip molding.

The production and properties of PVA capsules will be illustrated in the following examples and tests
EXAMPLE 1
Making a hard PVA capsule
To 3.50 kg of demineralized water, 5 g of potassium acetate (0.10% by weight in the solution) are added, followed by the addition of 10 = kappa-carrageenan (0.20% by weight). ) and 2% of Montane 80 (as anti-foaming agent, 0.04%) with stirring at about 70 ° C. When the kappa-carrageenan is dissolved, 1.35 kg (27% by weight) are added. ) of PVA (having a viscosity of 5 cps in aqueous solution at 4/0 to 20 ° C) at 600C with slow stirring until complete dissolution of the PVA and until the solution is no longer foaming.

 The thus prepared PVA solution is then poured into the molding cell of a pilot machine of conventional hard gelatin capsule manufacturing equipment.

While maintaining the temperature of the molding PVA solution at about 60 ° C., natural size transparent PVA capsules of size 0 and size 3 are made according to a conventional method with the same dimensional specifications as conventional hard gelatin capsules. As can be expected from the very low water vapor permeability of PVA, the drying time of the capsules is quite long.

EXAMPLE 2
Water vapor sorption of hard PVA capsules
The sorption isotherm of the PVA capsules of Example 1 was investigated and compared with the isotherm of hard gelatin capsules. Experiments show that PVA capsules have a much lower hygroscopicity than HGC.

 The results are shown in Figure 1.

EXAMPLE 3
Absorption of moisture from hard capsule fillings
The moisture absorption of packings encapsulated in PVA or HGC capsules was studied. The capsules were equilibrated at 22 ° C and 50% RH and then filled with dry polyvidone or dry corn starch After closure, the capsules were stored at 22 ° C and 50% relative humidity. Moisture absorption by the caps of the capsules was evaluated by increasing the weight of the full capsule. The experiments demonstrate that PVA capsules have an extremely low water vapor permeability.

 The kinetics of moisture absorption are shown in Figure 2.

Table 1 shows the ratio of the permeabilities of
PVA and hard gelatin capsule
Table 1

<tb><SEP> Filling <SEP> Polyvidone <SEP> Starch <SEP> of <SEP> but
<tb> Permeability <SEP> (capsule <SEP> of <SEP> PVA)
<tb><SEP> 0.017 <SEP> 0.027 <SEP>
<tb><SEP> Permeability <SEP> (HGC)
<Tb>
EXAMPLE 4
Behavior with perforation
In the BIL inhaler test conditions, size 3 capsules were perforated and their behavior examined. PVA capsules do not show any breakage or cracks in contrast to hard gelatin capsules and therefore have excellent piercing behavior even at low RH.

The test results are shown in Table 2
Table 2

<tb> RH <SEP> to <SEP> equilibrium <SEP> (%) <SEP> 50 <SEP> 10 <SEP> 2.5
<tb> HGC <SEP> broken <SEP> (%) <SEP> 0 <SEP> 30 <SEP> 100
<tb> Capsule <SEP> of <SEP> PVA <SEP> broken <SEP> (%) <SEP> 0 <SEP> 0 <SEP> 0
<Tb>
EXAMPLE 5
Dissolution test
Under USP 23 dissolution test conditions, the behavior was evaluated.
of size 0 and size 3 PVA capsules filled with acetaminophen in water
demineralized at 37 C. The PVA capsules have good properties of
dissolution.

 The results of the dissolution tests are shown in FIG.

Claims (30)

 1.- Film-forming compositions consisting of polyvinyl alcohol and setting system.  2. Film-forming compositions according to claim 1, wherein the setting system consists of hydrocolloids and cations.  3. Film-forming compositions according to claim 1, wherein the setting system optionally contains sequestering agents.  4. Film-forming compositions according to claim 1, wherein the polyvinyl alcohol is present in a proportion of 90 to 97% by weight, the water content is 2 to 7% by weight and the hydrocolloids are present in a proportion of 0, 0.1 to 10%, preferably 0.05 to 5% by weight, and the cations in a proportion of 0.001 to 5%, preferably 0.01 to 3% by weight.  5. Film-forming compositions according to claim 1, wherein the setting system optionally contains sequestering agents in a proportion of 0.01 to 5%, preferably 0.01 to 3% by weight of the composition.  6. Film-forming compositions according to claim 1, wherein the hydrocolloids of the setting system are selected from polysaccharides.  7. Film-forming compositions according to claim 1, wherein the hydrocolloids of the setting system are chosen from alginates, agar gum, guar gum, carob bean gum (carob), carrageenan, gum tara, gum arabic, ghatti gum, Khaya grandfolia gum, gum tragacanth, karaya gum, pectin, araban (araban), xanthan, gellan, starch, mannan Konjac, galactomannan or funorane.  8. Film-forming compositions according to claim 1, wherein the hydrocolloids of the setting system are selected from exocellular polysaccharides.  9. The film-forming compositions according to claim 1, wherein the hydrocolloids of the setting system are selected from xanthan, acetan, gellan, welan, rhamsane, ferrarane, succinoglycan, scleroglycan, schizophyllan, tamarind gum, curdlan, pullulan or dextran.  10. The film-forming compositions according to claim 1, wherein the hydrocolloids of the setting system are selected from gellan gum or kappa-carrageenan.  11. Film-forming compositions according to claim 1, in which the possible sequestering agents or sequestering agent mixtures of the setting system are chosen from ethylenediamine tetraacetic acid, acetic acid, boric acid, citric acid, Edetic acid, gluconic acid, lactic acid, phosphoric acid, tartaric acid or their salts, metaphosphates, dihydroxyethylglycine, lecithin or betacyclodextrin.  12. Film-forming compositions according to claim 11, wherein the sequestering agent or mixture of sequestering agents are chosen from ethylenediamine tetraacetic acid or its salts, or citric acid or its salts.  13. Film-forming compositions according to claims 1 to 12, further containing plasticizers in an amount of 0 to about 40% based on the weight of PVA.  14. Film-forming compositions according to claim 13, in which the plasticizer or the mixture of plasticizers is chosen from polyethylene glycol, glycerol, sorbitol, sucrose, corn syrup, fructose, sodium dioctyl sulfosuccinate, triethyl citrate and tributyl citrate. propylene glycol, mono-, di- or triacetate of glycerol, or natural gums.  15.- Film-forming compositions according to claims 1 to 14, further containing coloring agents in an amount of about 0 to 10% based on the weight of the PVA.  16. Film-forming compositions according to claim 15, in which the coloring agent or the mixture of coloring agents is chosen from azo, quinophthalone, triphenylmethane, xanthene or indigo dyes, iron oxides or hydroxides, titanium dioxide or natural dyes.  17. Film-forming compositions according to claim 16, in which the coloring agent or mixture of coloring agents is chosen from blue patent V, brilliant green acid BS, red 2G, azorubine, culvert 4R, amaranth, the red D + C 33, red D + C 22, red D + C 26, red D + C 28, yellow D + C 10, yellow 2 G, yellow FD + C 5, yellow FD + C 6, FD + C 3 red, FD + C 40 red, FD + C 1 blue, FD + C 2 blue, FD + C 3 green or BN brilliant black.  18. Film-forming compositions according to claim 15, in which the coloring agent or the mixture of coloring agents is chosen from carbon black, iron oxide black, iron oxide red, yellow d iron oxide, titanium dioxide, riboflavin, carotenes, anthocyanins, curcumin, cochineal extract, chlorophyllin, xanthaxanthin, caramel or betanin.  19.- Unit dosage form containers for agricultural chemicals, seeds, herbs, food products, coloring products, pharmaceuticals or flavoring agents obtained from the compositions according to any one of claims 1 to 18.  20. The container of claim 19, which is a pharmaceutical capsule.  21.- container according to claims 19 or 20, characterized in that it comprises a coating.  22. The coated container of claim 21, wherein the coating is selected from cellulose acetate phthalate, polyvinyl acetate phthalate, methacrylic acid gelatin, hypromellose phthalate, hydroxypropyl methylcellulose phthalate, hydroxyalkyl methylcellulose phthalate, or mixtures thereof.  23.- Grains encapsulated in film-forming compositions according to claims 1 to 18.  24.- Capsules according to claims 19 or 20, characterized in that the half-capsules are sealed with one or more layers of compositions according to claims 1 to 18.  Capsules according to claims 19 or 20, characterized in that the half-capsules are sealed by a liquid melting operation.  26. Aqueous solutions of compositions according to claims 1 to 18 for the manufacture of capsules.  27.- Aqueous solutions according to claim 26, containing polyvinyl alcohol in a proportion of 10 to 60%, preferably 20 to 40% by weight, hydrocolloids in a proportion of 0.01 to 5%, preferably 0, 03 to 1% by weight, and cations in an amount of 0.001 to 3%, preferably 0.01 to 1% by weight of the aqueous solution.  28. - Aqueous solutions according to claims 26 or 27, optionally containing sequestering agents in an amount of 0.001 to 5%, preferably 0.01 to 1% by weight of the aqueous solution.  29. The use of aqueous PVA solutions according to claims 26 to 9S for the manufacture of hard capsules by an immersion molding process.  30.- Manufacture of hard capsules from aqueous polyvinyl alcohol solutions according to claims 26 to 28, by a conventional equipment immersion dipping molding method and conventional hard gelatin capsule manufacturing parameters.