Title:  Polymer film compositions for capsules

United States Patent:  6,517,865

Issued:  February 11, 2003

Inventors:  Cade; Dominique (Colmar, FR); Scott; Robert (Sint-Niklaas, BE); He; Xiongwei (Colmar, FR)

Assignee:  Warner-Lambert Company (Morris Plains, NJ)

Appl. No.:  157428

Filed:  May 28, 2002

The present invention relates to non-animal polymer compositions suitable for film forming, particularly hard and soft capsules, comprising water soluble cellulose ethers, hydrocolloides and sequestering agents.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Suitable cellulose ethers for the present invention are alkyl and/or hydroxyalkyl substituted cellulose ether with 1 to 4 carbon atoms in the alkyl chains, preferably methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxyethylmethyl cellulose, hydroxyethylethyl cellulose, hydroxypropylmethyl cellulose or the like. Especially preferred is HBPMC. The amount of the cellulose ether or mixture of cellulose ethers is preferably 95 to 99.98% by weight. The viscosity of the cellulose ether or blend is 3 to 15 cps in 2% aqueous solution at 20^oC., preferred 5 to 10, especially preferred 6 cps.

Suitable hydrocolloids include such items as synthetic gums which are capable of gelling without the addition of alkaline or alkaline earth metal ions. The preferred gum for this purpose is gellan gum. Such gum, particularly including gellan gum, may be combined in mixtures producing synergistic properties which mixtures may also include natural seaweeds, natural seed gums, natural plant exudates, natural fruit extracts, bio-synthetic gums, bio-synthetic processed starch or cellulosic materials. More specifically, the mixture may include alginates, agar gum, guar gum, locust 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, funoran, and other exocellular polysaccharides of which are preferred the exocellular polysaccharides, such as xanthan, acetan, gellan, welan, rhamsan, furcelleran, succinoglycan, scieroglycan, schizophyflan, tamarind gum, curdlan, pullulan, dextran. The amount of gum present is preferably 0.01 to 2% by weight and especially preferred 0.1 to 1.0%.

The preferred sequestering agents are ethylenediaminetetraacetic acid, acetic acid, boric acid, citric acid, gluconic acid, lactic acid, phosphoric acid, tartaric acid or salts thereof methaphosphates, dihydroxyethylglycine, lecithin or beta cyclodextrin and combinations thereof Especially preferred is ethylenediaminetetraacetic acid or salts thereof or citric acid or salts thereof The amount is preferably 0.01 to 3%, especially 0.1 to 2% by weight.

The sequestering mechanism can be adjusted by addition of either monovalent or divalent cations, such a Ca++, Mg++, K+, Na+, Li+, NH4+ or the like.

Capsules or films with the inventive polymer composition may be manufactured with conventional machines by the conventional processes like extrusion moulding, injection moulding, casting or dip moulding.

The capsules and films have a non-animal polymer composition, an improved dissolution behavior, an enhanced elasticity and show higher transparency. The enhanced elasticity makes the capsules more useful for inhalation products. Furthermore the capsules are not sensitive to formaldehyde, for e.g. from a contaminated fill and they have a better temperature stability compared to gelatin capsules, because a crosslinking at storage on elevated temperatures does not occur.

The inventive polymer composition may contain additionally acceptable plasticizers in a range from about 0 to 40% based upon the weight of the cellulose ether. Suitable plasticizers are polyethylene glycol, glycerol, sorbitol, sucrose, corn syrup, fructose, dioctyl-sodium sulfosuccinate, triethyl citrate, tributyl citrate, 1,2-propylenglycol, mono-, di- or triacetates of glycerol, natural gums or the like as well as mixtures thereof.

The inventive polymer composition may contain in a further aspect additionally pharmaceutically or food acceptable coloring agents in the range of from about 0 to about 10% based upon the weight of the cellulose ether. The coloring agents may be selected from azo-, quinophthalone-, triphenylmethane-, xanthene- or indigoid dyes, iron oxides or hydroxides, titanium dioxide or natural dyes or mixtures thereof. Examples are patent blue V, acid brilliant green BS, red 2G, azorubine, ponceau 4R, amaranth, D+C red 33, D+C red 22, D+C red 26, D+C red 28, D+C yellow 10-, yellow 2G, FD+C yellow 5, FD+C yellow 6, FD+C red 3, D+C red 40, FD+C blue 1, FD+C blue 2, FD+C green 3, brilliant black BN, carbon black, iron oxide black, iron oxide red, iron oxide yellow, titanium dioxide, riboflavin, carotenes, anthocyanines, turmeric, cochineal extract, clorophyllin, canthaxanthin, caramel, or betanin.

The shaped polymer composition of the invention or the final product thereof may be coated with a suitable coating agent like cellulose acetate phthalate, polyvinyl acetate phthalate, methacrylic acid polymers, hypromellose phthalate, hydroxypropylmethyl cellulose phthalate, hydroxyalkyl methyl cellulose phthalates or mixtures thereof to provide e.g. enteric properties.

The polymer composition of the invention may be used for the production of containers for providing unit dosage forms for example for agrochemicals, seeds, herbs, foodstuffs, dyestuffs, pharmaceuticals, flavoring agents and the like.

The improved elasticity of the inventive polymer composition makes it useful for the encapsulation of caplets in a capsule, especially in a tamper-proof form. The encapsulation of a caplet in a capsule is preferred processed by cold shrinking together capsule parts, which are filled with a caplet, which comprises the steps providing empty capsule parts, filling at least one of said capsule parts with one or more caplets, putting said capsule parts together, and treating the combined capsule parts by cold shrinking.

The inventive polymer composition is also useful for encapsulating and sealing the two capsule halves in a process in which one or more layers of the composition are applied over the seam of the cap and body, or by a liquid fusion process wherein the filled capsules are wetted with a hydroalcoholic solution that penetrates into the space where the cap overlaps the body, and then dried.

Claim 1 of 21 Claims

What is claimed is:

1. A capsule material based on a polymer composition comprising:

a) 90 to 99.98% by weight of at least one cellulose ether having a water content of 2 to 10% and a viscosity of 3 to 15 cps measured in a 2% aqueous solution at 20^oC.;

b) 0.01 to 5% by weight of gellan gum; and

c) 0.01 to 8% by weight of a sequestering agent selected from the group consisting of ethylenediaminetetraacetic acid, sodium citrate, citric acid and combinations thereof.
 

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