WO2002009670A1 - Liquid or semi-solid pharmaceutical excipient and pharmaceutical composition comprising the same - Google Patents
Liquid or semi-solid pharmaceutical excipient and pharmaceutical composition comprising the same Download PDFInfo
- Publication number
- WO2002009670A1 WO2002009670A1 PCT/EP2000/007248 EP0007248W WO0209670A1 WO 2002009670 A1 WO2002009670 A1 WO 2002009670A1 EP 0007248 W EP0007248 W EP 0007248W WO 0209670 A1 WO0209670 A1 WO 0209670A1
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- WIPO (PCT)
- Prior art keywords
- pharmaceutical excipient
- castor oil
- pharmaceutical
- weight
- pharmaceutical composition
- Prior art date
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Classifications
-
- 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
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- 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
- A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
Definitions
- Liquid or semi-solid pharmaceutical excipient and pharmaceutical composition comprising the same
- the present invention relates to a liquid or semi-solid pharmaceutical excipient and a pharmaceutical composition comprising this excipient and a medicament.
- Excipients are additives used in the manufacture of pharmaceutical compositions, which allow the active ingredient or medicament to be incorporated in a pharmaceutical or galenic formulation which provides for the necessary bioavailability of the medicament upon the administration of the pharmaceutical composition.
- compositions may be administered to the patient to be treated in a number of ways, such as by oral, parenteral, intravenous, na- sal, topical, transdermal, rectal, perlingual, ocular or resperatorical administration.
- oral parenteral, intravenous, na- sal, topical, transdermal, rectal, perlingual, ocular or resperatorical administration.
- non-invasive ones are preferred, specifically the oral application, which allows a simple and easy use of the ' medicament by the patient himself.
- a number of medicaments are not suited for the oral application, specifically peptide medicaments, which are degraded upon oral administration during the gastro-intestinal passage, so that specifically with higher molecular medicaments, such as insulin, it is not possible to by oral application provide for the desired bio- availibility of the medicament.
- the object of the present invention therefore is the provision of a pharmaceutical excipient which allows for the manufacture of pharmaceutical for- mulations which enable the peroral administration of not only low molecular weight but also high molecular weight proteinaceous and specifically peptide medicaments, such as insulin etc.
- Subject-matter of the present invention therefore is the liquid or semi-solid pharmaceutical excipient according to claim 1.
- the subclai s comprise specific embodiments thereof and pharmaceutical compositions comprising this pharmaceutical excipient and a medicament.
- the present invention thus relates to a liquid or semi-solid pharmaceutical excipient comprising 0.1 to 98 % by weight, more preferably 5 to 75 % and specifically 38 to 45 % by weight of amphiphilic, nonionic, polyethoxylated castor oil mono-, di- or tri-esterified with a saturated or unsaturated, linear or branched C ⁇ -Ci8"f a t y acid (hereinafter termed "castor oil ester”) and the remainder water and/or one or more vegetable oils.
- castor oil ester a saturated or unsaturated, linear or branched C ⁇ -Ci8"f a t y acid
- Said castor oil preferably has a HLB value of 7 to 10.
- R ⁇ , R2 and R3 independently are hydrogen or saturated or unsaturated, linear or branched C 1 -C i s-fatty acid residues and 1, m and n independently are integers of from 1 to 20, with the proviso that at least one of R j , R2 and R3 is a saturated or unsaturated, linear or branched C1 - Cis'fa-tt acid residue and the sum 1+m+n is at least 15, preferably at least 20.
- R ⁇ , R2 and R3 independently are hydrogen or groups of formula:
- said castor oil ester is polyethoxylated glycerol oleoricinoleate comprising up to 20 and specifically 20 oxyethylene groups.
- This castor oil ester can be mixed with pharmaceutically acceptable vegetable oils to provide a clear mixture and which, as has been shown, is not toxic upon peroral administration to healthy adults as has been shown by corresponding clinical tests.
- Said castor oil esters can be manufactured according to the methods disclosed in for example U.S. -patents 4,597,906, 5 ,618,779 and 5 ,237,080, or are available on the market, such as the product sold by Th. Gold- schmidt AG, Essen, under the trade name TAGAT® V 20, having a Hess- Ives colour number of ⁇ 30, ahydroxyl value of 43 to 53, an acid value of ⁇ 7 and a saponification value of 100 to 120.
- the pharmaceutical excipient comprises 25 to 50 % by weight, more preferably 38 to 45 % by weight of said castor oil ester and 75 to 50 % by weight of one or more mono-, di- or tri-glycerides of saturated or unsaturated, linear or branched natural fatty acids. More preferably the excipient comprises said castor oil and said mono-, di- or tri-glycerides in a weight ratio of 10: 1 to 1 : 1 , more preferably in a weight ratio of 7.5:2.5.
- Said mon-, di- or tri-glyceride preferably is castor oil, peanut oil, almond oil and/or corn oil.
- the pharmaceutical excipient additionally comprises one or more physiologically acceptable synthetic or semi-synthetic ester oils, preferably esters of saturated Cg-C ⁇ g fatty acids, if desired in combination with linoleic acid and succinic acid with glycerol or propylene glycol, specifically caprylic/capric triglyce- rides, caprylic/capric /linoleic triglycerides, caprylic/capric /succinic tri- glycerides and propylene glycol dicaprylates/dicaprates, such as the products obtainable from CONDEA CHEMIE GmbH under the tradenames Miglyol® 810, 812, 829 and 840, or 4-methyl- l ,3-dioxalan-2-one.
- one or more physiologically acceptable synthetic or semi-synthetic ester oils preferably esters of saturated Cg-C ⁇ g fatty acids, if desired in combination with linoleic acid and succinic acid with gly
- the pharmaceutical excipient can further comprise 0.1 to 5 % by weight, more preferably 0.2 to 2 % by weight of a physiologically acceptable co-surfactant and/or a natural phospholipid.
- co-surfactant polyethoxylated sorbitan esters may be used, more preferably Polysorbate 60 or natural, semi-synthetic or synthetic phospholipids, preferably those which can provide liposomes.
- a physiologically acceptable antioxidant preferably a tocopherol derivative, such as tocopherol acetate.
- the above pharmaceutical excipient allows the manufacture of orally administrable pharmaceutical compositions comprising a medicament or ac- tive agent.
- Subject-matter of the present invention therefore is as a further embodiment a pharmaceutical composition
- a pharmaceutical composition comprising the above pharmaceutical excipient and a medicament.
- said pharmaceutical composition is perorally administrable and comprises the medicament dissolved or dispersed in said excipient.
- said pharmaceutical composition comprises the medicament in a hydrophilic ethanol/water phase dis- persed by said emulsifying castor oil ester as a water-in-oil emulsion, preferably in the form of a microdispersion in the hydrophobic vegetable oil phase.
- the medicament is a peptide type medicament, more preferably human or animal insulin, such as human or animal insulin in the form of an ethanol/water solubilized insulin preparation. It has been found by means of clinical tests on healthy adults that the oral administration of such an insulin dispersion applied in the form of an oral gelatine capsule comprising unit doses of up to 50 I.E. yields for 70 % of the test persons in comparison to placebo formulations a pharmacologically relevant and quick and very good reproducable reduction of the blood glucose level combined with a long activity duration.
- the pharmaceutical excipient of the present invention allows for the manufacture of a perorally administrable insulin formulation providing the desired bioavailability of the active agent in that obviously the formulation enables a large percentage of the intact molecules of the active agent to transgress the biological barriers of the intestine.
- the invention is explained in more detail on the basis of the following examples.
- the following components are used for the manufacture of the insulin microdispersion:
- Component Amount (% by weight)
- Polyethoxylated glycerol oleorizinoleate comprising 20 oxyethylene groups (TAGAT® V20) 36.85
- a 150 ml beaker is charged with the glycerol oleorizinoleate, the Polysorbitan 60 and the castor oil and is heated to 30°C while stirring with a magnetic stirrer to provide a clear mixture.
- the mixture is cooled to room tempera- ture following which the corn oil is added under stirring with the magnetic stirrer to provide a golden yellow transparent surfactant-oil-phase.
- a 20 ml beaker is charged with the purified water whereafter the sodium chloride is added and dissolved under stirring with a magnetic stirrer at room temperature. Thereafter the absolute alcohol is added at room temperature to provide a clear colorless solution to which the porcine insulin is added in 2 to 3 portions at room temperature while stirring with the magnetic stirrer until a homogenous, weakly opalescent insulin solubilisate is obtained.
- step I. The product of step I. is introduced in a beaker following which the hydrophilic insulin solubilisate is added slowly and continuously by means of a plastic syringe below the liquid surface under stirring at room temperature. Upon a preliminary turbidity a homogenous, weakly opalescent dispersion of the active agent is obtained, comprising 1.4 ml porcine insulin per gram of said dispersion.
- Said dispersion can be incorporated into gelatine capsules for the peroral administration of the medicament.
- Polyethoxylated glycerol oleorizinoleate comprising 20 oxyethylene groups (TAGAT® V 20) 37.70
- Oleum rizini (Ph. EU II) 25.20
- a 150 ml beaker is charged with the castor oil ester, the oleum rizini and corn oil in this sequence and is mixed at room temperature with a magnetic stirrer to provide a clear surfactant-oil-phase.
- the cetyl al- cohol is added to said mixture while heating to 40°C and stirring by means of a magnet stirrer to provide a clear solution, following which the silica is added in 4 to 5 portions under stirring, whereafter any air bubbles are removed, if necessary by applying a vacuum.
- microdisperse insulin formulation for peroral administration the following components are used:
- Components Amount (% by weight)
- Anhydrous lipogel (as manufactured in step I. above) 99.65 solid Porcine Insulin (28.5 I.U. / mg) 0.35
- the anhydrous lipogel For the manufacture of the pharmaceutical formulation 1 /3 of the anhydrous lipogel is introduced into a 150 ml beaker, whereafter the solid porcine insulin is added in small portions while stirring by means of a RPG- stirrer. Thereafter the residual amount of the anhydrous lipogel is added while stirring at room temperature and is then homogenized.
Abstract
Described are a liquid or semi-solid pharmaceutical excipient comprising 01 to 98 % by weight of amphiphilic, nonionic. polyethoxylated castor oil mono-, di- or tri-esterified with a saturated or unsaturated, linear or branched C14-C18-fatty acid and the remainder water and/or one or more vegetable oils and a pharmaceutical composition comprising an excipient and a medicament.
Description
Liquid or semi-solid pharmaceutical excipient and pharmaceutical composition comprising the same
Description
The present invention relates to a liquid or semi-solid pharmaceutical excipient and a pharmaceutical composition comprising this excipient and a medicament.
Excipients are additives used in the manufacture of pharmaceutical compositions, which allow the active ingredient or medicament to be incorporated in a pharmaceutical or galenic formulation which provides for the necessary bioavailability of the medicament upon the administration of the pharmaceutical composition.
Pharmaceutical compositions may be administered to the patient to be treated in a number of ways, such as by oral, parenteral, intravenous, na- sal, topical, transdermal, rectal, perlingual, ocular or resperatorical administration. Of these possibilities the non-invasive ones are preferred, specifically the oral application, which allows a simple and easy use of the ' medicament by the patient himself. However, a number of medicaments are not suited for the oral application, specifically peptide medicaments, which are degraded upon oral administration during the gastro-intestinal passage, so that specifically with higher molecular medicaments, such as insulin, it is not possible to by oral application provide for the desired bio- availibility of the medicament. The reason being that too high a number of the molecules of the medicament cannot pass the biological barriers of the intestine and will not provide for the necessary serum or tissue level. This is specifically problematic in case where exact levels of the medicament must be provided in the serum or tissue, such as in case of insulin.
Irrespective of the large amount of work done in view of trying to substitute the invasive forms of pharmaceutical formulations comprising higher molecular active agents by formulations which allow for the peroral application, this up to now has only been successful with respect to low molecular
weight peptide medicaments, such as cyclosporine.
The object of the present invention therefore is the provision of a pharmaceutical excipient which allows for the manufacture of pharmaceutical for- mulations which enable the peroral administration of not only low molecular weight but also high molecular weight proteinaceous and specifically peptide medicaments, such as insulin etc.
It has now been found that this problem can be solved by the use of a specif - ic liquid or semi-solid surfactant which can be used as a dispersant, solu- bilizer and/ or essential component of a perorally administrable pharmaceutical formulation, namely by the pharmaceutical excipient according to claim 1.
Subject-matter of the present invention therefore is the liquid or semi-solid pharmaceutical excipient according to claim 1. The subclai s comprise specific embodiments thereof and pharmaceutical compositions comprising this pharmaceutical excipient and a medicament.
The present invention thus relates to a liquid or semi-solid pharmaceutical excipient comprising 0.1 to 98 % by weight, more preferably 5 to 75 % and specifically 38 to 45 % by weight of amphiphilic, nonionic, polyethoxylated castor oil mono-, di- or tri-esterified with a saturated or unsaturated, linear or branched C ^ -Ci8"fat y acid (hereinafter termed "castor oil ester") and the remainder water and/or one or more vegetable oils.
Said castor oil preferably has a HLB value of 7 to 10.
An especially preferred embodiment of said castor oil corresponds to the following general formula (I):
wherein R^ , R2 and R3 independently are hydrogen or saturated or unsaturated, linear or branched C 1 -C i s-fatty acid residues and 1, m and n independently are integers of from 1 to 20, with the proviso that at least one of Rj , R2 and R3 is a saturated or unsaturated, linear or branched C1 - Cis'fa-tt acid residue and the sum 1+m+n is at least 15, preferably at least 20.
More preferably substitutents R} , R2 and R3 independently are hydrogen or groups of formula:
O
- C— (CH2)7— CB= CH- (CH2)7-CH3
Preferably said castor oil ester is polyethoxylated glycerol oleoricinoleate comprising up to 20 and specifically 20 oxyethylene groups.
This castor oil ester can be mixed with pharmaceutically acceptable vegetable oils to provide a clear mixture and which, as has been shown, is not toxic upon peroral administration to healthy adults as has been shown by corresponding clinical tests.
Said castor oil esters can be manufactured according to the methods disclosed in for example U.S. -patents 4,597,906, 5 ,618,779 and 5 ,237,080, or are available on the market, such as the product sold by Th. Gold-
schmidt AG, Essen, under the trade name TAGAT® V 20, having a Hess- Ives colour number of ≤ 30, ahydroxyl value of 43 to 53, an acid value of ≤ 7 and a saponification value of 100 to 120.
According to a preferred embodiment of the present invention the pharmaceutical excipient comprises 25 to 50 % by weight, more preferably 38 to 45 % by weight of said castor oil ester and 75 to 50 % by weight of one or more mono-, di- or tri-glycerides of saturated or unsaturated, linear or branched natural fatty acids. More preferably the excipient comprises said castor oil and said mono-, di- or tri-glycerides in a weight ratio of 10: 1 to 1 : 1 , more preferably in a weight ratio of 7.5:2.5.
Said mon-, di- or tri-glyceride preferably is castor oil, peanut oil, almond oil and/or corn oil.
According to a further preferred embodiment, the pharmaceutical excipient additionally comprises one or more physiologically acceptable synthetic or semi-synthetic ester oils, preferably esters of saturated Cg-C^g fatty acids, if desired in combination with linoleic acid and succinic acid with glycerol or propylene glycol, specifically caprylic/capric triglyce- rides, caprylic/capric /linoleic triglycerides, caprylic/capric /succinic tri- glycerides and propylene glycol dicaprylates/dicaprates, such as the products obtainable from CONDEA CHEMIE GmbH under the tradenames Miglyol® 810, 812, 829 and 840, or 4-methyl- l ,3-dioxalan-2-one.
If necessary the pharmaceutical excipient can further comprise 0.1 to 5 % by weight, more preferably 0.2 to 2 % by weight of a physiologically acceptable co-surfactant and/or a natural phospholipid. As such co-surfactant polyethoxylated sorbitan esters may be used, more preferably Polysorbate 60 or natural, semi-synthetic or synthetic phospholipids, preferably those which can provide liposomes.
It is in certain cases preferred to incorporate into the pharmaceutical excipient 0.1 to 0.5 % by weight of a physiologically acceptable antioxidant,
preferably a tocopherol derivative, such as tocopherol acetate.
The above pharmaceutical excipient allows the manufacture of orally administrable pharmaceutical compositions comprising a medicament or ac- tive agent.
Subject-matter of the present invention therefore is as a further embodiment a pharmaceutical composition comprising the above pharmaceutical excipient and a medicament. Preferably said pharmaceutical composition is perorally administrable and comprises the medicament dissolved or dispersed in said excipient.
According to a preferred embodiment said pharmaceutical composition comprises the medicament in a hydrophilic ethanol/water phase dis- persed by said emulsifying castor oil ester as a water-in-oil emulsion, preferably in the form of a microdispersion in the hydrophobic vegetable oil phase.
According to a preferred embodiment, the medicament is a peptide type medicament, more preferably human or animal insulin, such as human or animal insulin in the form of an ethanol/water solubilized insulin preparation. It has been found by means of clinical tests on healthy adults that the oral administration of such an insulin dispersion applied in the form of an oral gelatine capsule comprising unit doses of up to 50 I.E. yields for 70 % of the test persons in comparison to placebo formulations a pharmacologically relevant and quick and very good reproducable reduction of the blood glucose level combined with a long activity duration.
Thus, the pharmaceutical excipient of the present invention allows for the manufacture of a perorally administrable insulin formulation providing the desired bioavailability of the active agent in that obviously the formulation enables a large percentage of the intact molecules of the active agent to transgress the biological barriers of the intestine.
Hereinafter the invention is explained in more detail on the basis of the following examples.
EXAMPLE 1
Insulin Microdispersion
The following components are used for the manufacture of the insulin microdispersion:
Component Amount (% by weight)
Polyethoxylated glycerol oleorizinoleate comprising 20 oxyethylene groups (TAGAT® V20) 36.85
Polysorbitan 60 (Ph. EU II) 2.30
Castor oil (Ph. EU II) 25.35
Corn oil 27.65
Aqua purificata 3,45 NaCl (Ph. EU II) 0.46
Absolute Ethanol 3.80
Porcine Insulin (28.5 I.U. /mg) 0.14
100.00
I. Manufacture of a castor oil ester-oil-phase
A 150 ml beaker is charged with the glycerol oleorizinoleate, the Polysorbitan 60 and the castor oil and is heated to 30°C while stirring with a magnetic stirrer to provide a clear mixture. The mixture is cooled to room tempera- ture following which the corn oil is added under stirring with the magnetic stirrer to provide a golden yellow transparent surfactant-oil-phase.
II. Manufacture of a hydrophilic insulin solubilisate
A 20 ml beaker is charged with the purified water whereafter the sodium chloride is added and dissolved under stirring with a magnetic stirrer at room temperature. Thereafter the absolute alcohol is added at room temperature to provide a clear colorless solution to which the porcine insulin is added in 2 to 3 portions at room temperature while stirring with the magnetic stirrer until a homogenous, weakly opalescent insulin solubilisate is obtained.
III. Manufacture of the perorally administrable insulin dispersion
The product of step I. is introduced in a beaker following which the hydrophilic insulin solubilisate is added slowly and continuously by means of a plastic syringe below the liquid surface under stirring at room temperature. Upon a preliminary turbidity a homogenous, weakly opalescent dispersion of the active agent is obtained, comprising 1.4 ml porcine insulin per gram of said dispersion.
Said dispersion can be incorporated into gelatine capsules for the peroral administration of the medicament.
EXAMPLE 2
Anhydrous, perorally administrable insulin lipogel formulation
I. The following components are used for the manufacture of the lipogel:
Component Amount (% by weight)
Polyethoxylated glycerol oleorizinoleate comprising 20 oxyethylene groups (TAGAT® V 20) 37.70
Oleum rizini (Ph. EU II) 25.20
Corn oil 29.70
Cetyl alcohol (Ph. EU II) 1.70
Silica (Aerosil 200) (Ph. EU II) 5.70 100.00
A 150 ml beaker is charged with the castor oil ester, the oleum rizini and corn oil in this sequence and is mixed at room temperature with a magnetic stirrer to provide a clear surfactant-oil-phase. Following that, the cetyl al- cohol is added to said mixture while heating to 40°C and stirring by means of a magnet stirrer to provide a clear solution, following which the silica is added in 4 to 5 portions under stirring, whereafter any air bubbles are removed, if necessary by applying a vacuum.
II. For the manufacture of the anhydrous, microdisperse insulin formulation for peroral administration the following components are used:
Components Amount (% by weight)
Anhydrous lipogel (as manufactured in step I. above) 99.65 solid Porcine Insulin (28.5 I.U. / mg) 0.35
100.00
For the manufacture of the pharmaceutical formulation 1 /3 of the anhydrous lipogel is introduced into a 150 ml beaker, whereafter the solid porcine insulin is added in small portions while stirring by means of a RPG- stirrer. Thereafter the residual amount of the anhydrous lipogel is added while stirring at room temperature and is then homogenized.
Claims
1. A liquid or semi-solid pharmaceutical excipient comprising 0. 1 to 98 % by weight of amphiphilic, nonionic, polyethoxylated castor oil mono-, di- or tri-esterified with a saturated or unsaturated, linear or branched C 4-C ^g -fatty acid and the remainder water and/or one or more vegetable oils.
2. The pharmaceutical excipient according to claim 1 , wherein said castor oil ester has a HLB value of 7 to 10.
3. The pharmaceutical excipient according to claim 1 or 2, wherein said castor oil ester corresponds to the following general formula (I):
wherein Rj , R2 and R3 independently are hydrogen or saturated or unsaturated, linear or branched C^-Cjg-fatty acid residues and 1, m and n independently are integers of from 1 to 20, with the proviso that at least one of Rj , R2 and R3 is a saturated or unsaturated, linear or branched C24- C 28 -fatty acid residue and the sum 1+m+n is at least 15 , preferably at least 20.
4. The pharmaceutical excipient according to claim 3, wherein Rj , R2 and R3 independently are hydrogen or groups of formula:
P
- (CH2)7— CH= CH- (CH2)7-CH3
5. The pharmaceutical excipient according to any one of the preceeding claims, wherein said castor oil ester is polyethoxylated glycerol oleoricino- leate comprising 20 oxyethylene groups.
6. The pharmaceutical excipient according to any one of the preceeding claims, characterized in that it comprises 25 to 50 % by weight of said castor oil ester and 75 to 50 % by weight of one or more mono-, di- or tri-glycerides of saturated or unsaturated, linear or branched natural fatty acids.
7. The pharmaceutical excipient according to claim 6, characterized in that it comprises said castor oil ester and said mono-, di- or tri-glycerides in a weight ratio of 10: 1 to 1 : 1 , preferably 7.5 :2.5.
8. The pharmaceutical excipient according to claims 6 or 7, character- ized in that it comprises as said mono-, di- or tri-glyceride castor oil, peanut oil, almond oil and/ or corn oil.
9. The pharmaceutical excipient according to claim 6 to 8, characterized in that it further comprises one or more physiologically acceptable synthetic or semi-synthetic ester oils, preferably triglycerides and propylene glycol diesters with Cg-Cio fatty acids, if desired in combination with linoleic acid and succinic acid, and 4-methyl- l ,3-dioxaIan-2-one.
10. The pharmaceutical excipient according to any one of claims 1 to 9, characterized in that it further comprises 0.1 to 5 % by weight, preferably
0.2 to 2 % by weight of a physiologically acceptable co-surfactant and/or a natural, semi-synthetic or synthetic phospholipids, preferably those which can provide liposomes.
11. The pharmaceutical excipient according to claim 10, characterized in that it comprises as said co-surfactant a polyethoxylated sorbitan ester, preferably Polysorbate 60.
12. The pharmaceutical excipient according to any one of claims 1 to 1 1 , characterized in that it further comprises 0.1 to 0.5 % by weight of a physiologically acceptable antioxidant, preferably a tocopherol derivative, such as tocopherol acetate.
13. A pharmaceutical composition comprising a pharmaceutical excipient according to any one of claims 1 to 12 and a medicament.
14. The pharmaceutical composition according to claim 13, characterized in that it is perorally administrable.
15. The pharmaceutical composition according to claim 13 or 14, characterized in that it comprises the medicament dissolved or dispersed in said excipient.
16. The pharmaceutical composition according to claims 13 to 15, characterized in that it comprises the medicament in a hydrophilic ethanol/water phase dispersed by the emulsifying castor oil ester as a water- in-oil emulsion in the hydrophobic vegetable oil phase.
17. The pharmaceutical composition according to claims 13 to 16, characterized in that it comprises a peptide type medicament.
18. The pharmaceutical composition according to claim 17, characterized in that it comprises as said peptide type medicament human or animal insulin.
19. The pharmaceutical composition according to claim 18, characterized in that it comprises said peptide human or animal insulin as an ethanol/water solubilized insulin preparation.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/EP2000/007248 WO2002009670A1 (en) | 2000-07-27 | 2000-07-27 | Liquid or semi-solid pharmaceutical excipient and pharmaceutical composition comprising the same |
| AU2000261604A AU2000261604A1 (en) | 2000-07-27 | 2000-07-27 | Liquid or semi-solid pharmaceutical excipient and pharmaceutical composition comprising the same |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/EP2000/007248 WO2002009670A1 (en) | 2000-07-27 | 2000-07-27 | Liquid or semi-solid pharmaceutical excipient and pharmaceutical composition comprising the same |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2002009670A1 true WO2002009670A1 (en) | 2002-02-07 |
Family
ID=8164040
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP2000/007248 WO2002009670A1 (en) | 2000-07-27 | 2000-07-27 | Liquid or semi-solid pharmaceutical excipient and pharmaceutical composition comprising the same |
Country Status (2)
| Country | Link |
|---|---|
| AU (1) | AU2000261604A1 (en) |
| WO (1) | WO2002009670A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8062676B2 (en) * | 2005-08-02 | 2011-11-22 | Thomas Besendorfer | Pesticide composition |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0872542A2 (en) * | 1997-04-15 | 1998-10-21 | Th. Goldschmidt AG | Emulsified low-viscosity alkaline cleaners |
-
2000
- 2000-07-27 WO PCT/EP2000/007248 patent/WO2002009670A1/en active Application Filing
- 2000-07-27 AU AU2000261604A patent/AU2000261604A1/en not_active Abandoned
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0872542A2 (en) * | 1997-04-15 | 1998-10-21 | Th. Goldschmidt AG | Emulsified low-viscosity alkaline cleaners |
Non-Patent Citations (1)
| Title |
|---|
| MULLER, FELIX ET AL: "Thickening by dilution. New attempts for alkaline gel cleansers", SOFW J. (1997), 123(11), 746,748,750,752-753, XP000990080 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8062676B2 (en) * | 2005-08-02 | 2011-11-22 | Thomas Besendorfer | Pesticide composition |
| US20120064171A1 (en) * | 2005-08-02 | 2012-03-15 | Bedo Holding Ag | Pesticide Composition |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2000261604A1 (en) | 2002-02-13 |
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