Title:  High strength capsules, process of preparing and using the same

United States Patent:  6,165,503

Assignee:  FMC Biopolymer A.S. (Drammen, NO)

Filed:  July 1, 1998

Foreign Application Priority Data:  Jul 07, 1997[GB] (9714293)

In the formation of capsules having a polyanionic polysaccharide core and a polycationic polysaccharide membrane layer, improved binding of the polycationic polysaccharide is achieved by including polyvalent ions, especially calcium ions, at the membrane forming step.

SUMMARY OF THE INVENTION

It has now surprisingly been found that higher strength capsules of the type having a polyanionic polysaccharide core and a polycationic polysaccharide membrane can be formed by adding or providing a polyvalent ion, such as Ca²⁺, in the polyanion-polycation membrane forming step.

Accordingly, a first aspect of the present invention provides a process for preparing high strength capsules comprising the steps of:

(a) preparing gelled beads of a polyanionic polysaccharide which are cross-linked with a polyvalent cation,

(b) forming capsules having a polycation-polyanion membrane layer on the gelled beads by adding the beads to a solution comprising a polycationic polysaccharide,

(c) optionally forming one or more additional polycationic or polyanionic layers on the capsules, and

(d) harvesting the resulting capsules, characterised in that the process further includes the step of

(e) providing a polyvalent cation in the polycationic polysaccharide solution of step(b).

In a first embodiment of this aspect of the invention, step (a) comprises:

(i) providing a first solution comprising the polyanionic polysaccharide,

(ii) providing a second solution comprising the cross-linking polyvalent ions and a non-gelling ion, preferably sodium ions, and

(iii) adding the first solution in drops to the second solution, thereby to prepare homogeneous capsules.

In a second embodiment of this aspect of the is invention, the process of the invention further comprises providing a solution of a non-gelling ion, preferably sodium ions, and immersing the beads of step (a) in the solution of non-gelling ion, thereby to prepare homogeneous capsules.

In other preferred embodiments of this aspect of the invention, the process further comprises including an active ingredient, material or substance in the gelled bead of step (a). The active ingredient material or substance may advantageously be encapsulated in the gelled bead.

In a further embodiment of this aspect of the invention, the polyvalent cation in the membrane forming step (step (e)) is present at a concentration of from 50 mM to 400 mM, preferably 100 mM to 300 mM.

In preferred variations of the first and second embodiments of this aspect of the invention, the non-gelling ion is present at a concentration of at least 10 mM, more preferably 100 mM to 300 mM.

In another preferred variation of the first and second embodiments of this aspect of the invention, the membrane forming step (step (b)) proceeds for at least 15 minutes, preferably 2 to 5 hours, more preferably 30 minutes to 1 hour. Where a non-gelling ion is not employed, the membrane forming step (step (b)) preferably proceeds for at least 30 minutes, more preferably 2 to 5 hours and especially 1 to 2 hours.

A second aspect of the invention provides capsules obtainable by the process of the first aspect of the invention.

In preferred embodiments of this second aspect of the invention, the capsules contain a pharmaceutically active ingredient or composition. In further preferred embodiments of this aspect of the invention, the pharmaceutically active ingredient is selected from acid neutralising agents, local anaesthetics, histamine H₂ -receptor antagonists and antimicrobial agents.

Further aspects of the invention comprise the use of the capsules of the second aspect in therapy, more especially in the treatment of one or more of gastro-oesophageal reflux, sore throat, dyspepsia and/or heartburn, and Heliobacter pylori infections.

Additional aspects of the invention comprise the use of the capsules of the second aspect in the preparation of a medicament for the treatment of one or more of gastro-oesophageal reflux, sore throat, dyspepsia and/or heartburn, and Heliobacter pylori infections.

Claim 1 of 45 Claims

What is claimed is:

1. A process for preparing high strength capsules comprising:

(a) preparing gelled beads of a polyanionic polysaccharide which are cross-linked with a polyvalent cation,

(b) forming capsules having a polycation-polyanion membrane layer on the gelled beads by adding the beads to a solution comprising a polycationic polysaccharide,

(c) optionally forming one or more polycationic or polyanionic layers on the capsules, and

(d) harvesting the resulting capsules, wherein the process further comprises providing a polyvalent cation in the polycationic polysaccharide solution of (b).

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