Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Particulate form
Reexamination Certificate
2000-02-28
2002-07-09
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Particulate form
C424S499000, C424S501000, C424S502000
Reexamination Certificate
active
06416787
ABSTRACT:
THIS INVENTION relates to a quick-release composition. In particular, it relates to a method of making a water-dispersable composition, to an extrudable composition and to a dosage form suitable for the quick delivery in an aqueous environment such as the mouth, of an adjunct such as a medicine, flavourant, or the like.
According to a first aspect of the invention there is provided a method of making a water-dispersable composition, the method including
admixing together a polysaccharide, an enzyme capable of splitting the polysaccharide into smaller portions thereof, and a liquid, to form an admixture;
extruding the admixture at an elevated temperature to form an extrudate; and
cooling the extrudate, with the liquid evaporating from the extrudate as it cools, thereby forming a porous composition capable of disintegration when exposed to an aqueous environment.
The water-dispersable composition may be a quick-release composition, and may thus be capable of rapid disintegration when exposed to an aqueous environment.
By “quick-release composition” is meant a composition which will disintegrate rapidly, i.e. within 2 minutes when saturated with water; and the constituents, and the proportions thereof, should be selected by routine experimentation, to achieve this object.
According to a second aspect of the invention, there is provided a method of making a water-dispersable quick-release composition, the method including
extruding an at least partially destructurised starch at an elevated temperature in the presence of a blowing agent to form an extrudate; and
cooling the extrudate to form a porous composition capable of rapid disintegration when exposed to an aqueous environment.
The at least partially destructurising of the starch may be by means of the elevated temperature at which the extrusion is effected, by means of an enzyme capable of splitting the starch, by means of an acid or a base, or by a combination of two or more of these methods.
The partially destructurised starch may be in admixture with a pharmaceutically active agent or an adjunct. The blowing agent may be water.
The method may include admixing a pharmaceutically active agent into the admixture prior to or during the extrusion of the admixture.
Cooling the extrudate may include allowing the extrudate to cool at room temperature.
The method may include admixing an adjunct, such as a flavourant or the like, into the admixture prior to or during the extrusion of the admixture. More particularly, the adjunct may be selected from the group consisting of a flavourant, a preservative, an anti-oxidant, a surfactant, a colouring agent, a pH modifier, a sweetener, a taste masking agent, a plasticizer, a porosity modifying agent, or two or more thereof. The flavourant, when present, may be a mint flavourant, a lemon flavourant, an orange flavourant, a caramel flavourant, a vanilla flavourant, or the like. The pH modifier, when present, may be citric acid, tartaric acid, or the like. The taste masking agent, when present, may be sodium bicarbonate, an adsorbate, or the like, The plasticizer, when present, may be soya bean oil, polyethylene glycol, polyoxyethylene mono stearate, a light mineral oil, or an at least partially hydrated vegetable oil.
The polysaccharide may be starch and the liquid may be water, which may act as a blowing agent. The enzyme may be of the type which requires an aqueous environment to render it capable of splitting the starch.
The method may include cutting the extrudate, eg with a die face cutter, to provide discs or tablets or rods of the quick-release composition.
The starch and the enzyme may be initially present in the admixture, in a mass ratio of starch:enzyme from 10000;1 to 10:1. Preferably, the mass ratio of the starch to the enzyme in the admixture is from 10000:3 to 100:1, and most preferably, the mass ratio of the starch to the enzyme in the admixture is from 10000:5 to 1000:5.
The starch may be selected from the group consisting of corn starch, rice starch, wheat starch, oat starch, potato starch, or two or more thereof.
The water may be added to the admixture during the extruding by means of a pump. The water and starch may be Initially present, in the admixture, in a mass ratio of water:starch of 20:80 to 55:45. Preferably, the Initial mass ratio of the water to starch in the admixture is from 20:80 to 50:50, and most preferably, the initial mass ratio of the water to starch in the admixture is from 20:30 to 40:60, e.g. 30:70.
The polysaccharide or starch forms a carrier or excipient for the adjunct, and the carrier may also include sweeteners, e.g. sugars such as sucrose, dextrose, galactose and lactose. The sweetener may also be aspartame. Thus, the method may include adding a sugar to the admixture.
The enzyme is preferably a thermostable enzyme, such as the enzymes available in South Africa under the trade names THERMAMYL 120L and THERMAMYL 60 DT available from Enzymes South Africa (Proprietary) Limited, and manufactured by Novo Industri A/S, Denmark.
The pharmaceutically active agent may be a drug, such as theophylline, prochlorperazine maleate, paracetamol, or loperamyd, a vitamin such as vitamin A, B, C, D or E, and/or a mineral salt, such as calcium lactate, calcium phosphate, magnesium carbonate or magnesium lactate. The pharmaceutically active agent may function as an antacid, an antidepressant, an antihypertensive, an antimigraine, a hormone, or a urinary agent. The adjunct may be micro-encapsulated, so that It is substantially water-insoluble but soluble in the gut of a mammal, to mask the taste of the adjunct.
The elevated temperature at which the extruding of the admixture may be effected is from 80° C. to 135° C., preferably from 90° C. to 120° C. and most preferably from 100° C. to 120° C., e.g. 110° C.
Typically, extrusion of the admixture is with a screw extruder such as a twin-screw extruder, having a screw speed of from 50 to 200 rpm. The die cutter typically has a cutter speed of from 20 to 100 rpm. eg from 50 to 80 rpm and a diameter size of from 2 to 8 mm.
According to a third aspect of the invention, there is provided an extrudable composition comprising, in admixture with each other, a polysaccharide, a blowing agent and an enzyme capable of splitting the polysaccharide into smaller portions thereof.
The polysaccharide may be starch and the blowing agent may be water. The admixture may include a pharmaceutically active agent.
The composition may include an adjunct, which may be as hereinbefore described.
The enzyme may be present in the admixture at a concentration of from 0.01 to 10% m/m, based on the total admixture mass. Preferably, the concentration of the enzyme in the admixture is from 0.03 to 1% m/m, based on the total admixture mass, and most preferably, the concentration of the enzyme in the admixture is from 0.05 to 0.5% m/m, based on the total admixture mass, e.g. 0.1% m/m based on the total admixture mass.
The enzyme, starch and adjunct may be as hereinbefore described. The pharmaceutically active agent may be present in a concentration of up to 60% m/m, based on the total admixture mass.
The pharmaceutically active agent may be micro-encapsulated, so that it is substantially water-insoluble but dissolves when ingested by a mammal.
The admixture may include a sugar, such as dextrose, galactose and lactose or an artificial sweetener such as aspartame,
The invention extends to a dosage form obtained by extruding, at elevated temperature, an admixture comprising a pharmaceutically active agent and the extrudable composition as hereinbefore described.
The dosage form may have a diameter of from 5 to 10 mm and may comprise from 2 to 50 mg of the pharmaceutically active agent.
The pharmaceutically active agent may be as hereinbefore described.
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Le Hir, Abrégé de Pharmacie Galénique, formes pharmaceu
Dilova Emilia Dimitrova
Truter Patricia-Ann
van der Merwe Thilo Lothar
Frommer William S.
Frommer & Lawrence & Haug LLP
Implico B.V.
Page Thurman K.
Russell Mark W.
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