WO2005051347A2 - A simple process and formulation for making taste- masked ibuprofen liquid preparations and similar good-tasting preparation of other pharmaceutically active or bitter, poor tasting compounds for the production of liquid preparations - Google Patents
A simple process and formulation for making taste- masked ibuprofen liquid preparations and similar good-tasting preparation of other pharmaceutically active or bitter, poor tasting compounds for the production of liquid preparations Download PDFInfo
- Publication number
- WO2005051347A2 WO2005051347A2 PCT/GB2004/004424 GB2004004424W WO2005051347A2 WO 2005051347 A2 WO2005051347 A2 WO 2005051347A2 GB 2004004424 W GB2004004424 W GB 2004004424W WO 2005051347 A2 WO2005051347 A2 WO 2005051347A2
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- WIPO (PCT)
- Prior art keywords
- pharmaceutically active
- paste
- surfactant
- tasting
- liquid preparations
- Prior art date
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- Ceased
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Classifications
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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
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- 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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- 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
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- 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
- A61K9/10—Dispersions; Emulsions
Definitions
- TITLE A SIMPLE PROCESS AND FORMULATION FOR MAKING TASTE- MASKED IBUPROFEN LIQUID PREPARATIONS AND SIMILAR GOOD- TASTING PREPARATION OF OTHER PHARMACEUTICALLY ACTIVE OR BITTER, POOR TASTING COMPOUNDS FOR THE PRODUCTION OF LIQUID PREPARATIONS
- the present invention concerns a method and formulation for the simple and rapid manufacture of good-tasting liquid preparations of the analgesic ibuprofen and or other pharmaceutically active compounds (PAC).
- the method of formulation is straight forward and quick to manufacture.
- Ibuprofen is a very common, safe and widely available medicine, typically sold as coated tablet or caplets for adult consumption and as a very sweet syrup for the relief of pain and or fever in children.
- the invention is versatile because it is simple, of low cost and can taste- mask numerous insoluble PACs, whilst ensuring that in paste, syrup or ready to drink liquid delivery formats the PAC has the required stability for sale as licensed medicines or are otherwise fit for purpose EG as a soft drink format offering.
- the invention is the concept, process and formulation for the use of simple surfactants to completely taste-mask such poor-tasting PACs, of which ibuprofen is one example of many.
- Ibuprofen is a powerful and safe commonly used analgesic, with a wide range of uses, with more than 3 billion doses per annum sold in the USA. Ibuprofen when taken without coating or encapsulation is unpalatable; it delivers a powerful and unacceptable burning sensation to the roof of the mouth and the back of the throat. The sensation is not dissimilar to the consumption of hot chilli peppers, but with the burning sensation limited to two sites mentioned above. This organoleptic characteristic of the medicine has restricted the formats in which it can be delivered to consumers. An unacceptable taste is not unique to ibuprofen; many medicines, as well as other PACs (for example, the B6 vitamins or iron) share this draw back.
- PACs for example, the B6 vitamins or iron
- the current invention is a simple and novel means of delivering a stable PAC preparation in various liquid forms: ready to drink, paste and or syrup formulations, using a surfactant to form micelles around the pharmaceutically active compound and then further dispersing the micelles into a dilute solution of hydrocoUoid, for example carboxymethyl cellulose (CMC).
- CMC carboxymethyl cellulose
- the present invention is a very simple process for taste-masking a broad range of insoluble PACs for use in liquid preparations such as pastes, syrups and ready to drink formats.
- the process involves the simple dispersion of the PAC in a surfactant (or a similar or functionally analogous compound) to form micelles.
- This initial paste is then dispersed into a solution which contains a hydrocoUoid.
- This colloidal solution can then be directly homogenised, dispersed or stirred into a further solution containing all the typical ingredients necessary for flavouring liquids, for example flavourings, sweeteners, preservatives, colourings, antioxidants etc.
- the invention is the process and base formulation that allows the low cost and rapid preparation of a broad range of insoluble poor-tasting PACs to be treated such that when formulating low cost good-tasting pastes, syrups or ready to drink liquid PAC preparations.
- the process involves three steps: A) The homogeneous dispersion of the PAC(s) in a typically equal mass a surfactant, e.g. Tween 80 B) The further dispersion of the above paste into twice the final volume of water, containing a hydrocoUoid such as carboxymethyl cellulose, again using homogenisation or an analogous technique to effect a double coated micelle with hydrophobic, containing PAC and hydrophillic (miscibility in water) characteristics.
- a surfactant e.g. Tween 80
- this invention cannot be used as a replacement for the so-called slow-release tablets/extended-release (long- acting) tablets or capsules or enteric coated tablets or capsules to be administered sub-lingually and can only be applied to PACs normally administered orally.
- These Ready-to-Drink liquid medications can only be applied to those medicines that must pass through the stomach and be absorbed in the intestine for efficacy and excretion via the gastro-enteric route.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Biochemistry (AREA)
- Inorganic Chemistry (AREA)
- Dispersion Chemistry (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention involves the quick and simple dispersion of the pharmaceutically active compound, using a surfactant to form a paste with micelles that is subsequently dispersed into a solution of hydrocolloid. The resulting solution forms a base for the manufacture of a wide range of good-tasting pastes, syrups and ready to drink stable liquid pharmaceutically active preparations.
Description
PATENT APPLICATION
TITLE: A SIMPLE PROCESS AND FORMULATION FOR MAKING TASTE- MASKED IBUPROFEN LIQUID PREPARATIONS AND SIMILAR GOOD- TASTING PREPARATION OF OTHER PHARMACEUTICALLY ACTIVE OR BITTER, POOR TASTING COMPOUNDS FOR THE PRODUCTION OF LIQUID PREPARATIONS
ALL RIGHTS ARE EXCLUSIVELY OWNED BY: DR D.E Marshall (11 Hamilton Rd., Newmarket Suffolk CB8 ONQ)
FIELD OF THE INVENTION
The present invention concerns a method and formulation for the simple and rapid manufacture of good-tasting liquid preparations of the analgesic ibuprofen and or other pharmaceutically active compounds (PAC). The method of formulation is straight forward and quick to manufacture.
Ibuprofen is a very common, safe and widely available medicine, typically sold as coated tablet or caplets for adult consumption and as a very sweet syrup for the relief of pain and or fever in children.
All methodology currently available dramatically adds to the development time, manufacturing cycle and cost of goods. Also they are unsuitable for producing a good-tasting liquid preparation of ibuprofen in a therapeutic dose, especially in a ready to drink format, for example 400mg in 250ml, where the consumer simply opens a bottle and drinks the whole of its contents, as opposed to the inconvenient dispensing of 5ml or so of a syrup from a bottle containing numerous doses of the medicine. Such a ready to drink dose format does not exist in the market anywhere in the world today and is very distinct and new as a consumer proposition.
The invention is versatile because it is simple, of low cost and can taste- mask numerous insoluble PACs, whilst ensuring that in paste, syrup or ready to drink liquid delivery formats the PAC has the required stability for sale as licensed medicines or are otherwise fit for purpose EG as a soft drink format offering.
The invention is the concept, process and formulation for the use of simple surfactants to completely taste-mask such poor-tasting PACs, of which ibuprofen is one example of many.
BACKG OUND OF THE INVENTION
Ibuprofen is a powerful and safe commonly used analgesic, with a wide range of uses, with more than 3 billion doses per annum sold in the USA. Ibuprofen when taken without coating or encapsulation is unpalatable; it delivers a powerful and unacceptable burning sensation to the roof of the mouth and the back of the throat. The sensation is not dissimilar to the consumption of hot chilli peppers, but with the burning sensation limited to two sites mentioned above. This organoleptic characteristic of the medicine has restricted the formats in which it can be delivered to consumers. An unacceptable taste is not unique to ibuprofen; many medicines, as well as other PACs (for example, the B6 vitamins or iron) share this draw back.
Consumers are now placing more and more demand on convenience and speed of action. In addition, there is a strong and increasing demand for many products to be taken as a drink: the bottled water market continues to grow at nearly 20% per annum and bottled water consumption in the US is approaching beer consumption.
The only available liquid preparations of medicines are in syrup format, targeting the treatment of the very young and the very old: those that have difficulty with taking tablets or capsules. One of the key factors that restrict the development of ready to drink liquid formats of medicines has been the ability to delivery a good-tasting and stable preparation of PACs in water. Ibuprofen serves to illustrate this matter. Further the costs of taste-masking such compounds are usually comparable with the cost of the PAC in the preparation and this excludes such technology, normally
associated with tablets and capsules, from use in ready to drink liquid formulations.
The current invention is a simple and novel means of delivering a stable PAC preparation in various liquid forms: ready to drink, paste and or syrup formulations, using a surfactant to form micelles around the pharmaceutically active compound and then further dispersing the micelles into a dilute solution of hydrocoUoid, for example carboxymethyl cellulose (CMC). The effectiveness of the taste-masking, and its broad scope for use with numerous poor-tasting PACs over broad pHs, makes this simple process, which has been tested for manufacture, of significant commercial worth.
SUMMARY OF THE INVENTION
The present invention is a very simple process for taste-masking a broad range of insoluble PACs for use in liquid preparations such as pastes, syrups and ready to drink formats. The process involves the simple dispersion of the PAC in a surfactant (or a similar or functionally analogous compound) to form micelles. This initial paste is then dispersed into a solution which contains a hydrocoUoid. This colloidal solution can then be directly homogenised, dispersed or stirred into a further solution containing all the typical ingredients necessary for flavouring liquids, for example flavourings, sweeteners, preservatives, colourings, antioxidants etc.
3. DESCRIPTION OF THE INVENTION The invention is the process and base formulation that allows the low cost and rapid preparation of a broad range of insoluble poor-tasting PACs to be treated such that when formulating low cost good-tasting pastes, syrups or ready to drink liquid PAC preparations.
The process involves three steps: A) The homogeneous dispersion of the PAC(s) in a typically equal mass a surfactant, e.g. Tween 80 B) The further dispersion of the above paste into twice the final volume of water, containing a hydrocoUoid such as carboxymethyl cellulose, again using homogenisation or an analogous technique to effect a double coated micelle with hydrophobic, containing PAC and hydrophillic (miscibility in water) characteristics. C) The final dilution of the above dispersion into the finished beverage, or syrup possibly containing typically all known acidity regulators, flavourings or flavour enhancers, sweeteners, antioxidants, preservatives and other agents typical of such preparation and of the beverage industry D) Bottling and packing of the above solution into an appropriate container
4. LIMITATIONS
It is quite clear and obvious that this invention cannot be used as a replacement for the so-called slow-release tablets/extended-release (long- acting) tablets or capsules or enteric coated tablets or capsules to be administered sub-lingually and can only be applied to PACs normally administered orally.
These Ready-to-Drink liquid medications can only be applied to those medicines that must pass through the stomach and be absorbed in the intestine for efficacy and excretion via the gastro-enteric route.
EXAMPLE
The following specific example illustrate how the invention is or may be carried out, but should not be considered as limiting thereof in anyway.
The production of an ibuprofen liquid ready to drink aqueous solution with 400mg of ibuprofen in 250ml of finished product can be achieved very simply:
1) Disperse 400mg of 25 micron particle size ibuprofen (BASF) in 250mg of Tween 80 surfactant, using a Silverstone homogeniser.
2) Next add an equal volume of purified water containing a hydrocoUoid, for example carboxymβthyl cellulose, at concentration of Ig per 1000 ml of the final finished product.
3) Disperse again using the above apparatus or something analogous. The paste is now stable indefinitely at 4 degrees Celsius.
4) To prepare a finished beverage first disperse an aliquot of paste containing 400mg of ibuprofen into 125ml of an aqueous solution of anhydrous citric acid at 0.4% w/v, for the purpose of flavouring. Simple stirring will facilitate the dispersion of the ibuprofen paste. Next add a further amount to make up to 250ml final volume of a good- tasting beverage. For example, in batches of five litres:
Orange flavour at Ig/litre Fructose syrup at 560g in 5 litres Sodium benzoate at 0.75g in 5 litres Potassium sorbate at l.Og in 5 litres
This procedure has been checked for manufacturability in larger batch sizes and is clearly very simple and straight forward.
Claims
1. The dispersion of pharmaceutically active substances in a surfactant alone for subsequent use in the production of a liquid preparation, for example a paste, syrup or ready to drink beverage
2. As in 1 above where the surfactant is Tween 80 or an analogous surfactant
3. As in 1 and 2 above where the pharmaceutically active substance is ibuprofen or one of its active analogues
4. As in claims 1 to 3 inclusive where a paste is produced by combining the pharmaceutically active compound, or ensemble of one or more pharmaceutically active compounds in a preferred ratio of 1 : 1 w/w combination of pharmaceutically active ingredient to surfactant
5. As in claims 1 to 5 where the ratio stated in claim 4 lies between 1000: 1 to 1 : 1 and 1 : 1 to 1: 1000
6. As in claims 1 to 5 where combinations of non-surfactants are combined to produce a surfactant-like effect
7. As in claims 1 to 6 where additional compounds are added to aid the stability of the resulting paste, for example germicides, antibiotics, preservatives or any combination of substances with analogous function
8. As in any or all claims 1 to 8 where the resulting paste is further diluted to produce a more dilute paste which contains a hydrocoUoid
9. As in any or all claims 1 to 8 where the resulting paste is further diluted to produce a syrup
10. As in any or all claims 1 to 9 where the resulting paste is further diluted to produce a ready to drink beverage
11. As in claims 8 to 10 where the hydrocoUoid is carboxymethycellulose Ϊ2.AS in claims 8 to 11 where the hydrocoUoid is present in the finished product at lOOg/litre, more preferred at between 50g-5g/litre, even more preferred 5g-lg/litre, <lg/litre and most preferred at Ig per litre 13.As in claims 1 to 12 where at least one of the surfactants is Tween 80
4.As in claims 1 to 13 where these intermediates are subsequently made into a product for direct consumption by human or animals and containing acidity regulators (citric acid), flavourings, sweeteners, antioxidants, preservatives and other agents typically used in liquid or paste preparations
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0325321A GB2407497A (en) | 2003-10-30 | 2003-10-30 | Method and formulation for the rapid and stable taste-masking of insoluble pharmaceutically active compounds using a surfactant and a hydrocolloid |
| GB0325321.8 | 2003-10-30 | ||
| GB0400069.1 | 2004-01-03 | ||
| GB0400069A GB0400069D0 (en) | 2004-01-03 | 2004-01-03 | Process and formulation for taste-masking ibuprofen and other pharmaceutically active substances for the production of liquid preparations |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO2005051347A2 true WO2005051347A2 (en) | 2005-06-09 |
| WO2005051347A3 WO2005051347A3 (en) | 2006-01-05 |
Family
ID=34635426
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/GB2004/004424 Ceased WO2005051347A2 (en) | 2003-10-30 | 2004-10-19 | A simple process and formulation for making taste- masked ibuprofen liquid preparations and similar good-tasting preparation of other pharmaceutically active or bitter, poor tasting compounds for the production of liquid preparations |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2005051347A2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9205041B2 (en) | 2011-05-03 | 2015-12-08 | Aponia Laboratories, Inc. | Transdermal compositions of ibuprofen and methods of use thereof |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0179583A1 (en) * | 1984-10-04 | 1986-04-30 | Merck & Co. Inc. | A system for enhancing the water dissolution rate and solubility of poorly soluble drugs |
| GB8630273D0 (en) * | 1986-12-18 | 1987-01-28 | Til Medical Ltd | Pharmaceutical delivery systems |
| GB9625589D0 (en) * | 1996-12-10 | 1997-01-29 | Boots Co Plc | Therapeutic agents |
-
2004
- 2004-10-19 WO PCT/GB2004/004424 patent/WO2005051347A2/en not_active Ceased
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9205041B2 (en) | 2011-05-03 | 2015-12-08 | Aponia Laboratories, Inc. | Transdermal compositions of ibuprofen and methods of use thereof |
| US9849080B2 (en) | 2011-05-03 | 2017-12-26 | Aponia Laboratories, Inc. | Transdermal compositions of ibuprofen and methods of use thereof |
| US10821071B2 (en) | 2011-05-03 | 2020-11-03 | Aponia Laboratories, Inc. | Transdermal compositions of ibuprofen and methods of use thereof |
| US11419814B2 (en) | 2011-05-03 | 2022-08-23 | Aponia Laboratories, Inc. | Transdermal compositions of ibuprofen and methods of use thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2005051347A3 (en) | 2006-01-05 |
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