GB2390541A - Medicinal composition comprising fibre or saccharide bulking agents - Google Patents

Medicinal composition comprising fibre or saccharide bulking agents Download PDF

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Publication number
GB2390541A
GB2390541A GB0216147A GB0216147A GB2390541A GB 2390541 A GB2390541 A GB 2390541A GB 0216147 A GB0216147 A GB 0216147A GB 0216147 A GB0216147 A GB 0216147A GB 2390541 A GB2390541 A GB 2390541A
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United Kingdom
Prior art keywords
ingestible
ingestible composition
surfactant
composition
silica
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Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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GB0216147A
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GB0216147D0 (en
Inventor
Peter William Dettmar
Michael Edward Havler
Kevin Mckie
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Reckitt Benckiser Healthcare UK Ltd
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Reckitt Benckiser Healthcare UK Ltd
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Application filed by Reckitt Benckiser Healthcare UK Ltd filed Critical Reckitt Benckiser Healthcare UK Ltd
Priority to GB0216147A priority Critical patent/GB2390541A/en
Publication of GB0216147D0 publication Critical patent/GB0216147D0/en
Priority to PCT/GB2003/003040 priority patent/WO2004006692A1/en
Priority to DE60303449T priority patent/DE60303449T2/en
Priority to EP03738345A priority patent/EP1521535B1/en
Priority to US10/520,672 priority patent/US20050244519A1/en
Priority to AT03738345T priority patent/ATE316763T1/en
Priority to AU2003244869A priority patent/AU2003244869B2/en
Priority to MXPA05000549A priority patent/MXPA05000549A/en
Priority to ES03738345T priority patent/ES2256759T3/en
Publication of GB2390541A publication Critical patent/GB2390541A/en
Priority to ZA200409416A priority patent/ZA200409416B/en
Withdrawn legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/20—Reducing nutritive value; Dietetic products with reduced nutritive value
    • A23L33/21—Addition of substantially indigestible substances, e.g. dietary fibres
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/20—Reducing nutritive value; Dietetic products with reduced nutritive value
    • A23L33/21—Addition of substantially indigestible substances, e.g. dietary fibres
    • A23L33/22—Comminuted fibrous parts of plants, e.g. bagasse or pulp
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/20—Reducing nutritive value; Dietetic products with reduced nutritive value
    • A23L33/21—Addition of substantially indigestible substances, e.g. dietary fibres
    • A23L33/29—Mineral substances, e.g. mineral oils or clays
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/40—Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/734—Alginic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/68—Plantaginaceae (Plantain Family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/143—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/10—Laxatives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Abstract

An ingestible composition comprising a fibre or saccharide bulking agent, silica, and a surfactant, the composition being dispersable in water. Preferably, the fibre is plant-derived selected from cellulose or derivative thereof, a bran, or most preferably, ispaghula, a natural material of benefit in promoting good bowel function. The saccharide bulking agent is preferably polysaccharide-containing, more preferably an algin. Preferably, the surfactant is polyethylene-, polypropylene-, or polyoxyethylene-based. The preferred polyethylene-based surfactant is polyethylene glycol or a glycerol polyethylene glycol oxystearate. The preferred polyoxyethylene-based surfactant is a polyoxyethylene sorbitan fatty acid ester or a polyoxyethylene monostearate. Also, a method of making such an ingestible composition, the method comprising blending of the ingredients, preferably without the employment of isopropanol (or other solvent) or polyvinyl pyrrolidone (or any other granulating agent). The composition may help alleviate constipation and other digestive dysfunctions.

Description

Improvements In and Relating to Medicinal Compositions The present
invention relates to medicinal compositions comprising fibre or saccharine bulking agents.
Ingestible fibre- or saccharide-containing compositions for the relief of gastric and digestive dysfunctions are known. Examples of such compositions include granular psyllium husk fibre (ispaghula) intended to be stirred in 10 measured amounts into a volume of liquid, usually water or soft drinks. After stirring, the drinking composition is intended to be quickly imbibed due to the propensity of the ispaghula to absorb water readily and swell to form a viscous gel-like mass. It is the property of water 15 absorption which has the desired characteristic of fibre or saccharide-containing ingestible compositions for gastric and digestive dysfunctions. Once the fibre or saccharide-containing composition has absorbed water to produce the gel-like mass, the mass is relatively 20 insoluble and fibrous, and is transported through the gut quickly with minimal digestion, helping to alleviate constipation and other digestive dysfunctions.
Other forms, such as capsules forms for ingestion, are 25 also available, such capsules being designed to be broken down in the gut, wherein the released fibre or saccharine bulking agent absorbs water from the gut to form the viscous mass.
30 However, for beneficial ease-of-use properties, a particulate form is particularly advantageous to the end user, as this can be stirred into a volume of liquid, for a more pleasant taste, and the granular form of the fibre
or saccharide absorbs water from the gut more quickly than a capsule form. However, there are a number of problems involved in using a granular form of the fibre- or saccharide-containing ingestible compositions.
Primarily, it is desirable for the ingestible compositions to disperse easily in liquid, for the user's convenience and/or so that the resultant drink is more palatable and/or easier to swallow. Any new composition must be as lo good as or, preferably, better than, existing compositions in this respect.
Secondly, the handling of some ingestible fibre- or saccharide-containing compositions is not straightforward.
15 For example in commercial production ispaghula is milled then isopropyl alcohol and a granulating agent polyvinyl pyrollidone are added. These steps aid handling of the compositions during manufacturing, before the isopropyl alcohol is removed prior to packaging the product for 20 sale. The granulation also aids the dispersion of the ispaghula into a volume of liquid, prior to ingestion.
However, the use of the granulating agent and isopropyl alcohol increases the cost of production and the use of the isopropyl alcohol is undesirable from an environmental 25 and a health and safety perspective.
Thus, from the foregoing, it is apparent that there is a need for the provision of an ingestible composition which comprises a fibre or saccharide bulking agent, in which 30 the ingestible composition disperses easily in an aqueous liquid and/or is of improved manufacture.
It has now been determined that an ingestible composition comprising a fibre or saccharide bulking agent, which also includes an ingestible silica in conjunction with an ingestible surfactant, can offer benefit in the s manufacture of the ingestible composition, and can increase the rate at which the ingestible composition disperses in water or other ingestible liquid.
Therefore, according to the present invention there is lo provided an ingestible composition comprising a fibre or saccharine bulking agent, an ingestible silica, and an ingestible surfactant.
The presence of both an ingestible silica and an 15 ingestible surfactant can confer significant, eg synergistic, benefits. For example when the fibre or saccharide bulking agent is ispaghula the ternary composition has outstanding nettability properties, and is easy to manufacture, for example by simple blending.
Suitably the fibre or saccharide bulking agent is a natural ingestible fibre (by which term we include herein fibre extracts). Plant-derived fibre bulking agents are preferred, such as cellulose or derivatives thereof; 25 psyllium husk fibre (ispaghula); or brans such as corn, oat, wheat or rice brans. Animal-derived fibre, fruit-
derived fibre and/or synthetic ingestible fibres may also be used.
30 Particularly preferred as a fibre bulking agent is ispaghula.
The ispaghula may comprise whole ispaghula seeds, but preferably at least part of the ispaghula comprises separated ispaghula seed husks. More preferably the ispaghula comprises at least 50% wt separated ispaghula 5 husks, most preferably at least 95% wt separated ispaghula husks. Suitably the remainder of the ispaghula comprises other seed parts and/or other ispaghula plant materials.
In preferred compositions the seed kernels themselves have been substantially removed to leave the husks.
If the bulking agent is a saccharide-containing bulking agent it is suitably a polysaccharide, preferably an algin, especially alginic acid or a salt derivative thereof, such as calcium alginate, magnesium alginate, 5 sodium alginate or potassium alginate.
Algins may be found in and isolated from various organisms, in particular from algae belonging to the order Phaeophyceae and soil bacteria such as Azotobacter 20 vinelandii and Azotobacter crococcum and from several strains of Pseudomonas bacteria. Common algal sources of algins include Laminaria digitata, Ecklonia maxima, Macrocystis pyrifera, Lessonia nigrescens, Ascophyllum nodosum, Laminaria japonica, Durvllea antartica, 25 Durvillea potatorum and, especially, Laminaria hyperborea.
Alginic acid is a linear hetero-polyeaccharide comprising units of B-Dmannuronic acid and a-L-guluronic acid.
Alginic acid may comprise homopolymeric sequences of 30 mannuronic acid, homopolymeric sequences of guluronic acid, and mixed sequences of mannuronic acid and guluronic acid units.
Salts of alginic acid used may include alkali metal salts, for example sodium and potassium salts, and ammonium and alkanolamine salts. Alkali metal salts are of particular interest. The term "algins" as used herein includes alginic acid and salts of alginic acid, irrespective of the relative proportion of mannuronic and guluronic units, and is intended to include glycolated or alkoxylated derivatives, 0 especially those derivatised with propylene glycol.
However, preferred compounds are not alkoxylated or glycolated. Suitably the silica is fumed or precipitated synthetic or 15 natural silica. The silica may be amorphous or crystalline. Suitably the mean particle size of the silica is at least 5nm, preferably at least lOnm.
Suitably the mean particle size of the silica is up to 5pm, preferably up to 0.75pm, more preferably up to 0.5pm, and most preferably up to 0.2pm.
25 The silica material that is used may typically contain 0.1 to 2.5wt% alumina (A12O3), preferably 0.5 to 2wt' alumina, and most preferably about lwt% alumina, based on the weight of the silica.
30 One suitable silica material is Syloid 244 which is amorphous silica, has a mean particle size of about 3pm and is provided by W R Grace & Co. Another suitable
silica materials is Silox 15,also from W R Grace & Co., and which has a mean particle size of about 4pm.
Another suitable silica material is Huber Zep 49 which is 5 amorphous silica from J M Huber Corporation and contains about 1 wt' alumina.
Another suitable silica is Aerosil 200 from Degussa Company. It contains less than 0.05 wt% alumina and has a lo mean particle size of 12 nm.
Preferably the silica is colloidal silica, and a preferred silica is a colloidal silica which is sold under the trade mark CAB-O-SIL, by Cabot Inc. USA.
Suitably the specific surface area of the silica is at least 50m2 gl, preferably at least 150m2 gl.
Suitably the specific surface area of the silica is up to 20 400m2 gl' preferably up to 300m2 gl most preferably up to 200m2 g1 Suitably the silica is present in the ingestible composition in an amount at least O. Olwt%, preferably at 25 least 0.05wt%, more preferably at least O.lwt% and most preferably at least 0.25wt%, of the total weight of the ingestible composition.
Suitably the silica is present in the ingestible 30 composition in an amount up to 5wt%, preferably up to 2wt%, more preferably up to lwt, and most preferably up -
to 0.6wt%, of the total weight of the ingestible composition.
Preferably the ingestible surfactant is a polyethylene-, polypropylene-, or polyoxyethylene-based surfactant.
Suitable polyethylene or polyoxyethylene-based surfactants 5 include polyethylene glycols and polyoxyethylene sorbitan fatty acid esters (polysorbates).
Suitable polyethylene glycols have a molecular weight of between 200 and 40,000, preferably between 200 and 1,000, 10 and more preferably between 200 and 600. Suitable polyethylene glycols include MACROGOLD and MACROGOLUM polyethylene glycols sold by ICI Surfactants, UK. Other suitable surfactants include polyoxyethylene monostearates and glycerol polyethylene glycol oxystearates.
Suitably the surfactant is present in the ingestible composition in an amount at least 0.01wt%, preferably at least 0.05wt%, more preferably at least 0.1wt%, and most preferably at least 0.2wt%, of the total weight of the 20 ingestible composition.
Suitably the surfactant is present in the ingestible composition in an amount up to 5wt%, preferably up to 3wt%, more preferably up to 2wt% and most preferably up to 25 lwt%, of the total weight of the ingestible composition.
When the surfactant is polyethylene glycol it is preferably present is an amount at least 0.1wt%, more preferably at least 0.3wt%, of the total weight of the 30 ingestible composition.
When the surfactant is polyethylene glycol it is preferably present is an amount up to 2wt%, more
preferably up to 1.5wt%, of the total weight of the ingestible composition.
When the surfactant is a polyoxyethylene sorbitan fatty 5 acid ester it is preferably present in an amount at least O.Olwt%, more preferably at least 0.05wt%, and most preferably at least 0.08wt%, of the total weight of the ingestible composition.
lO When the surfactant is a polyoxyethylene sorbitan fatty acid ester it is preferably present in an amount up to 2wt%, more preferably up to lwt%, and most preferably up to 0.5wt%, of the total weight of the ingestible composition. The percentages stated represent the total complement of the silica and surfactant, that is, summated if there is more than one silica or surfactant in the composition.
20 The ingestible composition may further comprise ingestible coingredients such as a bicarbonate for example sodium bicarbonate, an ingestible acid, for example citric acid, a flavouring, or a colouring, for example.
25 Preferably the ingestible composition does not contain a granulating agent.
Most preferably the ingestible composition does not contain polyvinyl pyrollidone.
Preferably the ingestible composition does not contain any residue of polyvinyl alcohol.
Suitably the composition is provided in a particulate solid form, for example as a powder or flakes, intended to be mixed with water, prior to ingestion by a user.
Alternatively the composition may be provided as a capsule 5 for dispersal in a liquid, for drinking by a user.
Preferably the composition is provided in a particulate form. In accordance with a second aspect of the present lo invention there is provided a method of making an ingestible composition comprising a fibre or saccharide bulking agent, an ingestible silica, and an ingestible surfactant, the method comprising the step of blending the fibre or saccharide bulking agent with the ingestible 15 silica and the ingestible surfactant.
Preferably no isopropyl alcohol is used in the manufacture. 20 More preferably no solvent of any type is used in the manufacture. Preferably no polyvinyl pyrollidone is used in the manufacture. More preferably no granulating agent of any type is used in the manufacture.
The fibre or saccharide bulking agent may be milled prior 30 to the blending step, suitably to a mean particle size in the range 250-450pm.
Preferably the method does not include the granulation of the bulking agent.
The fibre or saccharide bulking agent may be subjected to 5 a sterilization step prior to the blending step.
Irradiation may employ steam or, preferably, a radioactive source, for example a y-radiation source, for example from a Cobalt-60 or Caesium-137 source. A suitable radiation dosage is up to 13 kGy, preferably 5-10 kGy.
The invention will now be described by way of example in which the following materials are used throughout: Ispaghula - Ispaghula husk material obtained from Plantago 15 ovate, broken down to enable the seed kernels to be removed. The material was dried, irradiated with y-
radiation from a Caesium-137 source at a dosage rate of about 7 kGy, as described in PCT/GBO1/02040, and milled to a mean particle size of 300400pm.
CAB-O-SIL (Trade Mark) - A colloidal silica having a specific surface area in the range 175-225m2g manufactured by Cabot Inc. USA.
25 TWEEN 60 (Trade Mark) - A polyoxyethylene sorbitan fatty acid ester, manufactured by ICI.
TWEEN 80 (Trade Mark) - A polyoxyethylene sorbitan fatty acid ester, manufactured by ICI.; Propylene glycol.
Cremophore RH40 - Glycerol polyethylene glycol oxysterate, manufactured by BASF.
Pricerine - Porcine glyerine, supplied by Uniquema.
PEG 200 - Polyethylene glycol, molecular weight approximately 200, manufactured by Clariant.
Liquid surfactants were added slowly to the ispaghula as 10 it was being mixed in a domestic-style MAGIMIXER (Trade Mark). Mixing was continued until the ispaghula appeared evenly covered (dampened).
Solid surfactants were ground in a pestle and mortar and 15 then added to the ispaghula and placed in an oven (60-
70 C) for 30 minutes. The samples were then quickly blended in the MAGIMIXER as above.
To the ispaghula blended with surfactant as described 20 above was added a colloidal silica sample (CAB-O-SIL) in an attempt to dust the samples dry and improve flow characteristics (but also - as will be seen - with the unexpected result that the wetting characteristics of the final product were greatly improved).
No granulation step took place; no granulating agent was used.
Test methods 1. Wettability (dispersion in water) This was the most important test used to assess the effectiveness of each treatment and simply involved slowly spreading an amount of the formulation containing 3.5g ispaghula onto the surface of 150ml of cold tap water lo contained in a 200ml Pyrex beaker, and recording the time taken for all the material to become fully wetted without using any agitation to quicken the process.
2. Water absorbency/swell volume This test determines the swell volume (ml) or ability of a product to take up water. This is a key property for the mechanism of action of ispaghula, and hence disruption/reduction to this effect would certainly impact 20 on efficiency.
The method is as follows: Add lg of ispaghula (or the equivalent wt of product 25 containing lg ispaghula) to lOOml of tap water in a lOOml measuring cylinder, mix thoroughly by shaking and allow to stand. At 1 and 2 hours mix again by gentle inversion, and allow to stand for a further 2 hours. At the end of this period (4 hours from start), record the level of 30 mucilage/gel in the measuring cylinder. Typically, this will be 40-50ml per gramme of ispaghula.
3. Gel/flow rate on hydration This method is used to gain an insight into the rate of gel/mucilage formation. Although gelling is an important 5 attribute, the initial onset has been delayed in ingestible ispaghula compositions to allow the consumer to ingest it, over a period of a few minutes, as a palatable drink. lo A weight of sample containing 3.5g ispaghula is mixed into 150ml cold tap water in a 200ml beaker. At 5 minute intervals after making up, the time taken for lOOml of the sample to run through a Flow Cup (No. 5) viscometer is recorded. This is basically a brass cup which holds 15 exactly lOOml, with a tapered bottom leading to a standard-sized hole. As a sample gels, then the time taken for lOOml to flow through increases.
4. Carr's Index Carr's index is a measurement of bulk density of pharmaceutical powders, measured in a Copley Erweka Tapped Volumeter, model SVM-22. Powder is placed in a vertical cylinder which is "tapped" in the machine to aid the 25 settlement of the powder, and the percentage change in volume measured, over the predetermined test period/regime, identical for each sample.
Example 1
In this series of tests the wetting ability of ternary ispaghula + PEG 200 + CAB-O-SIL compositions was assessed, and compared with non-ternary compositions. The
Nettability was measured after 5 minutes, 16-24 hours and 8 days; there is reason from work on other compositions to believe that Nettability can decrease as the interval from manufacture increases.
As will be seen, there were three replicates All three results are given in Tables 1-3 below.
In each test the measurement was of time (sees) for a dose lo of treated ispaghula (3.5g) to disperse.
Tables 1-3
PEG 200 CAB-O-SIL 5 mine after manufacture CAB-O-SIL level" (wt%) PEG 200 _ _ _
levels (wt%) 0.3 0.5 0.4 -- - 5,5,5 7,5,6
_ _ 0.8 7,8,7 6,5,5
__ 1.2 6,4,4 6,7,7
_ Comparisons: no PEG 200, no CAB-O-SIL: 270, 310, 330 no PEG 200, 0.3 wt% CAB-O-SIL: 165, 170, 165 0.4 wet PEG 200, no CAB-O-SIL: 120, 130, 135
PEG 200 + CAB-O-SIL 16-24 hour" after manufacture CAB-O-SIL level" (wt%) PEG 200
levels (wt%) 0.3 0.5 0.4 6,6,6 7,5,7
0.8 20,20,20 6,5,6
_ 1.2 11,12,11 12,11,12
5 Comparisons: no PEG 200, no CAB-O-SIL: not measured no PEG 200, 0.3 wt% CAB-O-SIL: 330, 330, 350 0.4 wt% PEG 200, no CAB-O-SIL: 305, 320, 320 PEG 200 CAB-O-SIL 8 days after manufacture CAB-O-SIL levels (wt%) PEG 200
levels (wt%) 0.3 0.5 0.4 11,12,11 10,6,7
0.8 25,25,30 8,8,8
1.2 22,30,26 15,17,15
Comparisons: no PEG 200, no CAB-O-SIL: 310, 300, 280 no PEG 200, 0.3 wt% CAB-O-SIL: 1800, 1200, 15 0.4 wt% PEG 200, no CAB-O-SIL: 470, 480, 510 Example 2
This series of tests were as Example 1, but used TWEEN 80 20 instead of PEG 200, and different time intervals. In
these tests ispaghula alone was not tested. The results are given in Tables 4-6 below. Again, in each test the measurement was of time (sees) for a dose of treated ispaghula (3.5g) to disperse (n=3).
Tables 4-6
TWEEN 80 + C8-O-SIL 5 mins after manufacture CAB-O-SIL levels (wt%) _ _ _ _
TWEEN 80
level (wt%) 0.3 0.5 0.09 21,16,17 20,17,20
0.14 7,7,8 8,5,8
_... _ _
0.20 4,4,5 4,4,4
- Comparisons: no TWEEN 80, no CAB-O-SIL: not measured no TWEEN 80, 0.3 wt% CAB-O-SIL: 180, 215, 225 O.O9wt% TWEEN 80, no CAB-O-SIL: 75, 80, 75 15 TWEEN 80 + CAB-O-SIL 72 hours after manufacture CAB-O-SIL levels (wt%) _ __ _ _
TWEEN 80
levels (wt%) 0.3 0.5 _. ...
0.09 25,25,30 30,22,25
_._ 0.14 10,13,11 10,10,9
0.20 - 6,5,4 - 4,5,5
Comparisonn: no TWEEN 80, no CAB-O-SIL: not measured no TWEEN 80, 0.3 wt% CAB-O-SIL: 495, 450, 480 20 O.O9wt% TWEEN 80, no CAB-O-SIL: 63, 70, 60
TWEEN 80 + CAB-O-SIL 7 days after manufacture CAB-O-SIL levels (wt%) TWEEN 80 0.3 0.5
levels (wt%) 0.09 36,27,32 35.35,35
- 0.14 10,10,12 10,9,8
0.20 7,7,6 4,5,5
5 Comparisons: no TWEEN 80, no CAB-O-SIL: not measured no TWEEN 80, 0.3 wt% CAB-O-SIr: 735, 795, 930 0.09wt TWEEN 80, no CAB-O-SIL: 75, 67, 78 Again the results for the ternary system are remarkable, 10 much better than either binary system.
Example 3
This test was used primarily to assess long term 5 Nettability properties. Obviously such properties are extremely important for a commercial product.
As before, each experiment employed 3.5g of ispaghula in the composition, except that for the swell volume test lg 20 of composition was used.
The compositions were placed in a cycling oven, cycling between 4 C and 30 C. The samples were tested immediately on preparation, after 5 weeks incubation in the cycling 25 oven, and after 3 months incubation the cycling oven. As an exception, compositions including CAB-O-SIL and PEG 200
were tested immediately and after 9 weeks incubation only.
The results of the experiment are shown in Table 7.
- R.,,:
3 Ail E! 4)to m ul or o or 54 ffl 6 U H N H N N r 1,_' N r N 1 H R H = ul an _ 34)E4, at u, Hi N m^ Rffl.3 o u, 3 C Ala __ C U N N N
- 1 'A 4) U or m O In D v r N N N U7 H o H _' N O O O O d. H C r4 R R 0 3 3 U 3 3 0 R u 3 R R RCRl o3 o 0 tO ffl dP 3 dP 3 a 3 3 3 0 3 h + H O + H O 3 h N E ul | I I 0 1 o 1 1 0 1 H + o | + o | + + |
The results show that the addition of all of the tested combinations of ingestible silica in combination with an ingestible surfactant, substantially reduces the time taken for the ispaghula to disperse in a 150ml beaker of 5 cold water (wet/ability). The Nettability time is significantly reduced on initial testing and remains reduced through the 5 week samples and the 3 month samples. 10 In particular, polyethylene glycol and TWEEN in combination with CAB-O-SIL show a marked ability to reduce the Nettability time of untreated ispaghula husk compared to other combinations of surfactant with CAB-O-SIL. The results therefore indicate that ingestible compositions 15 comprising surfactant plus CAB-O-SIL mixed with ispaghula husk are also shelf stable at ambient temperatures (between 4 C and 30 C) over a sustained period of time.
Example 4
The tests corresponded to those of Example 3 but the compositions were tested by incubating at 40 C in an incubating oven. The samples were tested immediately on preparation, after 5 weeks incubation and after 3 months 25 incubation. AS an exception, compositions containing CAB-
O-SIL and PEG 200 were tested immediately and after 9 weeks incubation only. The results of the experiment are shown in Table 8.
_ _ O r N O '- U iD O 0 tar {D u 0 v E m <A or u m^ 3 m O N O O m Al u, u, in 0 v E co or into or 3 > E O O O O
0 U H on An AD to to01 _ _ 10 A; I a; of 1 oP + oP + O I R v 3 3 3 o 0 3 3 0 0 0 0 la 3 P0 3 =03 =3 3 3 h U o + + H a 3 u v3 O O Ve O O O H E co _ z)- +CDO +DO + +U) +C.)o +ChO + +U)

Claims (18)

Claims
1. An ingestible composition comprising a fibre or saccharide bulking agent, an ingestible silica, and an ingestible surfactant.
2. An ingestible composition as claimed in claim 1 wherein the composition comprises a plant-derived fibre bulking agent selected from: cellulose or a derivative thereof; ispaghula; or a bran.
3. An ingestible composition as claimed in claim 1 or 2 wherein the fibre bulking agent is ispaghula.
4. An ingestible composition as claimed in claim 1 wherein the bulking agent is a polyeaccharide-containing bulking agent comprising an algin.
5. An ingestible composition as claimed in any preceding claim wherein the particle size of the silica is between 5nm and 5pm.
6. An ingestible composition as claimed in any preceding claim wherein the specific surface area of the silica is between 50 and 400gm2.
7. An ingestible composition as claimed in any preceding claim wherein the silica is present in an amount of between O.Olwt% and 5wtt of the total weight of the ingestible composition.
8. An ingestible composition as claimed in any preceding claim, wherein the ingestible surfactant is a
polyethylene-, polypropylene-, or polyoxyethylene-based surfactant.
9. An ingestible composition as claimed in claim 8 wherein the polyethylenebased surfactant is a polyethylene glycol.
10. An ingestible composition as claimed in claim 9 wherein the polyethylene glycol has a molecular weight of between 200 and 40,000, preferably between 200 and 1,000.
11. An ingestible composition as claimed in claim 8 wherein the polyoxyethylene-based surfactant is a polyoxyethylene sorbitan fatty acid ester.
12. An ingestible composition as claimed in claim 8, wherein the surfactant is a polyoxyethylene monostearate or a glycerol polyethylene glycol oxystearate.
13. An ingestible composition as claimed in any preceding claim wherein the ingestible surfactant is present in an amount of between O.Olwtt and 5wt% of the total weight of the ingestible composition,
14. An ingestible composition as claimed in claim 13 wherein the ingestible surfactant is polyethylene glycol and is present in an amount of between O.lwt% and 2wt% of the total weight of the ingestible composition.
15. An ingestible composition as claimed in claim 13 wherein the surfactant is a polyoxyethylene sorbitan fatty acid ester and is present in an amount of between lwt% and 2wt% of the total weight of the ingestible composition.
16. A method of making an ingestible composition comprising a fibre or saccharine bulking agent, an ingestible silica, and an ingestible surfactant, the method comprising the step of blending the fibre or saccharide bulking agent with the ingestible silica and the ingestible surfactant; preferably without the employment of isopropyl alcohol or more preferably of any solvent; and preferably without the employment of polyvinyl pyrollidone or more preferably of any granulating agent.
17. An ingestible composition or its manufacture substantially as described herein.
Is A'' Amendmente to the claims have been filed as follows Claims 1. An ingestible composition comprising a fibre bulking agent selected from ispaghula or a bran, an ingestible, silica, and an ingestible surfactant.
2. An ingestible composition in particulate or granular form comprising a fibre or saccharide bulking agent, an ingestible silica, and an ingestible surfactant.
3. An ingestible composition as claimed in claim 1 or wherein the fibre bulking agent is ispaghula.
4. An ingestible composition as claimed in claim 2 wherein the bulking agent is a polysaccharide-containing bulking agent comprising an algin.
5. An ingestible composition according to claim 2 wherein the fibre bulking agent is cellulose or a derivative thereof. 6. An ingestible composition as claimed in any preceding claim wherein the particle size of the silica is between 5nm and 5pm.
7. An ingestible composition as claimed in any preceding claim wherein the specific surface area of the silica is between 50 and 400gm2.
8. An ingestible composition as claimed in any preceding claim wherein the silica is present in an amount of between O.Olwt% and 5wtt of the focal weight of the ingestible composition.
fit L À 1: 1
I I, c c L I L À C À
C e C
2k 9. An ingestible composition as claimed in any preceding claim, wherein the ingestible surfactant is a polyethylene-; polypropylene-, or polyoxyethylene-based surfactant. 10. An ingestible composition as claimed in claim wherein the polyethylene-based surfactant is a -
polyethylene glycol.
11. An ingestible composition as claimed in claim 10 wherein the polyethylene glycol has a molecular weight of between 200 and 40,000, preferably between 200 and 1,000.
12. An ingestible composition as claimed in claim 9 wherein the polyoxyethylene-based surfactant is a polyoxyethylene sorbitan fatty acid ester.
13. An ingestible composition as claimed in claim 9, wherein the surfactant is a polyoxyethylene monostearate or a glycerol polyethylene glycol oxystearate.
14. An ingestible composition as claimed in any preceding -
claim wherein the ingestible surfactant is present in an amount of between O.Olwt% and 5wt% of the total weight of the ingestible composition.
15. An ingestible composition as claimed in claim 14 wherein the ingestible surfactant is polyethylene glycol and is present in an amount of between O.lwt% and 2wt% of the total weight of the ingestible composition.
L I t C C t t I C t C L e C t L L. L ( L L L t c t t C L À t t L
t l 16. An ingestible composition as claimed in claim 14 wherein the surfactant is a polyoxyethylene sorbitan fatty acid ester and is present in an amount of between lwt% and 2wt% of the total weight of the ingestible composition'.
17. A method of making an ingestible composition comprising a fibre or saccharide bulking agent, an I ingestible silica, and an ingestible surfactant, the method comprising the step of blending the fibre or saccharide bulking agent with the ingestible silica and the ingestible surfactant; preferably without the employment of isopropyl alcohol or more preferably of any solvent) and preferably without the employment of polyvinyl pyrollidone or more preferably of any granulating agent.
18. An ingestible composition or its manufacture substantially as described herein.
C L L L L:
À À I L L I
L L I I C I L L
C L I
À À À I À I L
À À L L
GB0216147A 2002-07-12 2002-07-12 Medicinal composition comprising fibre or saccharide bulking agents Withdrawn GB2390541A (en)

Priority Applications (10)

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GB0216147A GB2390541A (en) 2002-07-12 2002-07-12 Medicinal composition comprising fibre or saccharide bulking agents
ES03738345T ES2256759T3 (en) 2002-07-12 2003-07-11 COMPOSITION OF IMPROVED VOLUME INCREASE AGENT.
US10/520,672 US20050244519A1 (en) 2002-07-12 2003-07-11 Bulking agent compositions
DE60303449T DE60303449T2 (en) 2002-07-12 2003-07-11 IMPROVED FILLING COMPOSITIONS
EP03738345A EP1521535B1 (en) 2002-07-12 2003-07-11 Improved bulking agent composition
PCT/GB2003/003040 WO2004006692A1 (en) 2002-07-12 2003-07-11 Improved bulking agent compositions
AT03738345T ATE316763T1 (en) 2002-07-12 2003-07-11 IMPROVED FILLER COMPOSITIONS
AU2003244869A AU2003244869B2 (en) 2002-07-12 2003-07-11 Improved bulking agent compositions
MXPA05000549A MXPA05000549A (en) 2002-07-12 2003-07-11 Improved bulking agent compositions.
ZA200409416A ZA200409416B (en) 2002-07-12 2004-11-23 Improved bulking agent compositions

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IL187793A0 (en) * 2005-06-23 2008-08-07 Martek Biosciences Corp Process for obtaining lipid from cells
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US4731246A (en) * 1985-10-31 1988-03-15 Product Resources International, Inc. Liquid bran drink
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GB2258810A (en) * 1991-08-12 1993-02-24 Euro Celtique Sa Pharmaceutical combination formulation of diltiazem and hydrochlorothiazide
US6030988A (en) * 1996-04-23 2000-02-29 Janssen Pharmaceutica, N.V. Immediate release pH-independent solid dosage form of cisapride

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US20050244519A1 (en) 2005-11-03
ATE316763T1 (en) 2006-02-15
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