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WO2013115746A1 - A production method for (effervescent) pharmaceutical compositions comprising an alpha - glucosidase inhibitor (miglitol) and metformin - Google Patents

A production method for (effervescent) pharmaceutical compositions comprising an alpha - glucosidase inhibitor (miglitol) and metformin Download PDF

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Publication number
WO2013115746A1
WO2013115746A1 PCT/TR2013/000055 TR2013000055W WO2013115746A1 WO 2013115746 A1 WO2013115746 A1 WO 2013115746A1 TR 2013000055 W TR2013000055 W TR 2013000055W WO 2013115746 A1 WO2013115746 A1 WO 2013115746A1
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Prior art keywords
production method
formulation
miglitol
metformin
effervescent
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PCT/TR2013/000055
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French (fr)
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Mahmut Bilgic
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    • 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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/133—Amines having hydroxy groups, e.g. sphingosine
    • 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
    • A61K31/13—Amines
    • A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • 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
    • A61K31/702—Oligosaccharides, i.e. having three to five saccharide radicals attached to each other by glycosidic linkages
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
    • A61K9/0007—Effervescent

Definitions

  • the present invention relates to a process used in production of the effervescent formulations comprising an alpha-glucosidase inhibitor and metformin as the active agent that shall be used in improving glycemic control in adults suffering from non-insulin dependent diabetes (type 2) wherein hyperglycaemia cannot be controlled by diet or exercise.
  • Alpha-glucosidase inhibitors are a group of active agents which affect blood sugar level positively by preventing the digestion of carbohydrates and therefore production of monosaccharides which are absorbed through the intestine.
  • the active agents belonging to said group are principally voglibose, acarbose and miglitol.
  • Voglibose (Basen®) is in 0.2 and 0.3 mg tablet dosage forms on the market. As for Miglitol (Glyset®) and acarbose (PRECOSE®), they are in 25, 50 and 100 mg tablet dosage form on the market.
  • Tablet dosage form frequently used in the prior art has disadvantages for pediatric and geriatric patients and for those who have swallowing difficulties and therefore alternative dosage forms are needed.
  • suspension forms are not mostly preferred for the reasons that they carry the possibility of uncontrolled dose intake, their production costs are high, they have physical and chemical instability problems, they cause problem during use and carrying phases.
  • suspension forms have higher bioavailability values as compared to solid dosage forms, it is seen that they are more inconvenient than solid dosage forms when viewed in terms of stability and shelf-life.
  • Effervescent dosage forms can overcome the problems encountered in solid dosage forms in the prior art.
  • Effervescent formulations comprise high amount of effervescent acid and effervescent base in order to obtain sufficient dispersion in water. This situation considerably increases unit dosage weight.
  • this type of formulations having high unit dosage weight is compressed in tablet form, various problems are encountered.
  • said effervescent tablet dosage forms are obtained by dry methods such as dry blending or dry granulation, the formulations cannot be formed into dosage forms which have desired hardness value after tablet compression and this poses problems for the manufacturers during packaging and carrying.
  • the wet granulation method that can be used as an alternative to dry methods in production of the effervescent formulations may cause undesirable results since it causes the effervescent acid and effervescent base to react during production. This results in obtainment of pretty large granules, failure to dry the granules efficiently and problems in stability of the product obtained due to the reaction.
  • the present invention relates to a method for production of effervescent formulations comprising miglitol and metformin as the active agent.
  • a characteristic feature of the method preferred for production of the effervescent formulations of the present invention is that metformin is subjected to granulation process in said production method.
  • Another characteristic feature of the method preferred for production of the effervescent formulations of the present invention is that metformin is granulated separately from the excipients comprised in the formulation in said production method.
  • the effervescent tablets with sufficient tablet hardness and the formulations having superior stability characteristics are obtained by producing metformin by wet granulation method and by preventing the contact of the active agent with the other substances comprised in the formulations during production.
  • the present invention relates to a method that shall be used in production of the effervescent formulations comprising miglitol and metfomin as the active agent, characterized in that said method is composed of the following steps:
  • the production method of the present invention is composed of the following steps:
  • the granulation solvent in the granulation solution prepared in the I st and V th steps of the production method water, ethanol, methanol, acetone, ethyl acetate, hexane, heptane, n-octane, n-butyl acetate, propanol, t-butyl alcohol, dichloromethane or aqueous HCI solution, aqueous NaOH solution or a combination thereof can be used.
  • water is used as the granulation solvent.
  • At least one pharmaceutically acceptable excipient that can be used in the V th and VIII th steps of the production method can be selected from a group comprising binder, lubricant, sweetener, flavouring agent.
  • At least one pharmaceutically acceptable excipient that shall be used in the I st and II nd steps of the production method is preferably binder.
  • the binders that shall be used in these two steps can be identical or different binders.
  • Metformin used in the effervescent formulations produced by the production method of the present invention is in the form of a pharmaceutically acceptable salt thereof, preferably in the form of metformin hydrochloride.
  • the effervescent formulations produced by the production method of the present invention comprise miglitol in the range of 1% to 80%, preferably in the range of 1% to 70%, more preferably in the range of 1% to 50% in proportion to unit dosage weight and metformin in the range of 1% to 80%, preferably in the range of 1% to 70%, more preferably in the range of 1% to 50% in proportion to unit dosage weight.
  • the ratio of miglitol to metformin used as the active agent in the effervescent formulations produced by the production method of the present invention is in the range of 0.01-8 by weight, preferably in the range of 0.03-5 by weight, more preferably in the range of 0.05-1 by weight.
  • the present invention relates to a production method for the effervescent formulations which dissolve or disperse in water or a similar solvent in less than 10 minutes, preferably in the range of 1 to 8 minutes, more preferably in the range of 1 to 5, for instance in the range of 1.5, 2, 2.5, 3 to 3.5, 4, 4.5 minutes and which comprise miglitol and metformin as the active agent.
  • the effervescent acid that can be used in the effervescent formulations produced by the production method of the present invention and comprising miglitol and metformin as the active agent can be selected from a group comprising organic acids such as malic acid, citric acid, tartaric acid, fumaric acid; the effervescent base can be selected from a group comprising agents such as sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate or combinations thereof.
  • the lubricant that can be used in the effervescent formulations produced by the production method of the present invention and comprising miglitol and metformin as the active agent can be selected from a group comprising calcium stearate, magnesium stearate, polyethylene glycol, sodium benzoate, potassium benzoate, sodium lauryl sulphate, talc, stearic acid, zinc stearate or combinations thereof.
  • the binder that can be used in the effervescent formulations produced by the production method of the present invention and comprising miglitol and metformin as the active agent can be selected from a group comprising carboxymethyl cellulose sodium, ethyl cellulose, gelatine, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hypromellose, magnesium aluminium silicate, maltodextrin, methyl cellulose, povidone, starch or combinations thereof.
  • the sweetener and/or taste-regulating agent that can be used in the effervescent formulations produced by the production method of the present invention and comprising miglitol and metformin as the active agent can be selected from a group comprising acesulphame, aspartame, dextrose, fructose, maltitol, maltose, mannitol, saccharin, saccharin sodium, sodium cyclamate, sorbitol, sucralose, sucrose, xylitol, sodium chloride or combinations thereof.
  • the flavouring agent that can be used in the effervescent formulations produced by the production method of the present invention and comprising miglitol and metformin as the active agent can be selected from menthol, lemon, orange, vanilla, strawberry, raspberry, caramel and similar flavours or combinations thereof.
  • Another characteristic feature of the formulations produced by the production method of the present invention is that said formulations comprise miglitol and metformin as the active agent and their tablet hardness value is in the range of 3 kP to 50 kP.
  • formulations produced by the production method of the present invention comprise miglitol and metformin as the active agent and their tablet hardness value is in the range of 4 kP to 40 kP.
  • formulations produced by the production method of the present invention comprise miglitol and metformin as the active agent and their tablet hardness value is in the range of 5 kP to 30 kP.
  • EXAMPLE 1 Effervescent formulation comprising the combination of miglitol and metformin and production method
  • the first granulation The granulation solution comprising the granulation solvent and the binder is prepared.
  • the mixture obtained by mixing the effervescent acid, the effervescent base and the binder is granulated with the granulation solution; the granules are dried and sieved.
  • the second granulation The granulation solution comprising the granulation solvent and the sweetener is prepared. Metformin is granulated with this granulation solution. The granules are dried and sieved.
  • the granules obtained by the first and the second granulation processes are mixed with miglitol, the lubricant and the flavouring agent and compressed in tablet dosage form.

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Description

A PRODUCTION METHOD FOR (EFFERVESCENT) PHARMACEUTICAL COMPOSITIONS COMPRISING AN ALPHA-GLUCOSIDASE INHIBITOR (MIGLITOL) AND METFORMIN
The present invention relates to a process used in production of the effervescent formulations comprising an alpha-glucosidase inhibitor and metformin as the active agent that shall be used in improving glycemic control in adults suffering from non-insulin dependent diabetes (type 2) wherein hyperglycaemia cannot be controlled by diet or exercise.
Alpha-glucosidase inhibitors are a group of active agents which affect blood sugar level positively by preventing the digestion of carbohydrates and therefore production of monosaccharides which are absorbed through the intestine. The active agents belonging to said group are principally voglibose, acarbose and miglitol.
Voglibose (Basen®) is in 0.2 and 0.3 mg tablet dosage forms on the market. As for Miglitol (Glyset®) and acarbose (PRECOSE®), they are in 25, 50 and 100 mg tablet dosage form on the market.
Tablet dosage form frequently used in the prior art has disadvantages for pediatric and geriatric patients and for those who have swallowing difficulties and therefore alternative dosage forms are needed.
An alternative for solid oral dosage forms such as tablet may be to formulate the pharmaceutical formulation in suspension form. However suspension forms are not mostly preferred for the reasons that they carry the possibility of uncontrolled dose intake, their production costs are high, they have physical and chemical instability problems, they cause problem during use and carrying phases. Although suspension forms have higher bioavailability values as compared to solid dosage forms, it is seen that they are more inconvenient than solid dosage forms when viewed in terms of stability and shelf-life.
Thanks to the studies they conducted, the inventors have found that effervescent dosage forms can overcome the problems encountered in solid dosage forms in the prior art. Effervescent formulations comprise high amount of effervescent acid and effervescent base in order to obtain sufficient dispersion in water. This situation considerably increases unit dosage weight. When this type of formulations having high unit dosage weight is compressed in tablet form, various problems are encountered. In the case that said effervescent tablet dosage forms are obtained by dry methods such as dry blending or dry granulation, the formulations cannot be formed into dosage forms which have desired hardness value after tablet compression and this poses problems for the manufacturers during packaging and carrying. On the other hand, it has been seen that this type of formulations comprising one of the alpha-glucosidase inhibitors such as voglibose, acarbose or miglitol as the active agent has low compressibility and this situation poses some problems in tableting.
The wet granulation method that can be used as an alternative to dry methods in production of the effervescent formulations may cause undesirable results since it causes the effervescent acid and effervescent base to react during production. This results in obtainment of pretty large granules, failure to dry the granules efficiently and problems in stability of the product obtained due to the reaction.
When the prior art is taken into consideration, there is still need for new production methods that can be used in production of effervescent formulations comprising miglitol and metformin as the active agent wherein stabile products having the required hardness value are obtained. According to this, the present invention relates to a method for production of effervescent formulations comprising miglitol and metformin as the active agent.
A characteristic feature of the method preferred for production of the effervescent formulations of the present invention is that metformin is subjected to granulation process in said production method. Another characteristic feature of the method preferred for production of the effervescent formulations of the present invention is that metformin is granulated separately from the excipients comprised in the formulation in said production method.
In the scope of the present invention, it has been seen that the effervescent tablets with sufficient tablet hardness and the formulations having superior stability characteristics are obtained by producing metformin by wet granulation method and by preventing the contact of the active agent with the other substances comprised in the formulations during production.
In another aspect, another characteristic feature of the method preferred for production of the effervescent formulations of the present invention is that miglitol is not subjected to granulation process in said production method. The formulations obtained this way minimize the stability problems arising from the reaction of migl itol with the other substances comprised in the formulation. According to this, the present invention relates to a method that shall be used in production of the effervescent formulations comprising miglitol and metfomin as the active agent, characterized in that said method is composed of the following steps:
• Granulating the mixture comprising at least one effervescent acid, at least one effervescent base and at least one pharmaceutically acceptable excipient with the granulation solution comprising a granulation solvent and optionally one or more excipients and drying them,
• Granulating metformin with the granulation solution optionally comprising one or more excipients, drying them and • Mixing miglitol and at least one excipient with the granules obtained in the first two steps.
The production method of the present invention is composed of the following steps:
I. Preparing a granulation solution comprising a granulation solvent and optionally one or more excipients,
II. Mixing at least one effervescent acid, at least one effervescent base and at least one excipient,
III. Granulating the mixture obtained in the IInd step with the granulation solution prepared in the Ist step,
IV. Drying the granules,
V. Preparing a granulation solution comprising a granulation solvent and optionally one or more excipients,
VI. Granulating metformin with the granulation solution prepared in the Vth step,
VII. Drying the granules,
VIII. Adding miglitol and at least one excipient into the granules obtained in the IVth and VIIth steps and mixing them,
IX. Compressing the formulation obtained in tablet dosage form.
As the granulation solvent in the granulation solution prepared in the Ist and Vth steps of the production method; water, ethanol, methanol, acetone, ethyl acetate, hexane, heptane, n-octane, n-butyl acetate, propanol, t-butyl alcohol, dichloromethane or aqueous HCI solution, aqueous NaOH solution or a combination thereof can be used. Preferably, water is used as the granulation solvent.
At least one pharmaceutically acceptable excipient that can be used in the Vth and VIIIth steps of the production method can be selected from a group comprising binder, lubricant, sweetener, flavouring agent.
At least one pharmaceutically acceptable excipient that shall be used in the Ist and IInd steps of the production method is preferably binder. The binders that shall be used in these two steps can be identical or different binders.
Metformin used in the effervescent formulations produced by the production method of the present invention is in the form of a pharmaceutically acceptable salt thereof, preferably in the form of metformin hydrochloride.
The effervescent formulations produced by the production method of the present invention comprise miglitol in the range of 1% to 80%, preferably in the range of 1% to 70%, more preferably in the range of 1% to 50% in proportion to unit dosage weight and metformin in the range of 1% to 80%, preferably in the range of 1% to 70%, more preferably in the range of 1% to 50% in proportion to unit dosage weight. The ratio of miglitol to metformin used as the active agent in the effervescent formulations produced by the production method of the present invention is in the range of 0.01-8 by weight, preferably in the range of 0.03-5 by weight, more preferably in the range of 0.05-1 by weight.
In another aspect, the present invention relates to a production method for the effervescent formulations which dissolve or disperse in water or a similar solvent in less than 10 minutes, preferably in the range of 1 to 8 minutes, more preferably in the range of 1 to 5, for instance in the range of 1.5, 2, 2.5, 3 to 3.5, 4, 4.5 minutes and which comprise miglitol and metformin as the active agent.
The effervescent acid that can be used in the effervescent formulations produced by the production method of the present invention and comprising miglitol and metformin as the active agent can be selected from a group comprising organic acids such as malic acid, citric acid, tartaric acid, fumaric acid; the effervescent base can be selected from a group comprising agents such as sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate or combinations thereof. The lubricant that can be used in the effervescent formulations produced by the production method of the present invention and comprising miglitol and metformin as the active agent can be selected from a group comprising calcium stearate, magnesium stearate, polyethylene glycol, sodium benzoate, potassium benzoate, sodium lauryl sulphate, talc, stearic acid, zinc stearate or combinations thereof.
The binder that can be used in the effervescent formulations produced by the production method of the present invention and comprising miglitol and metformin as the active agent can be selected from a group comprising carboxymethyl cellulose sodium, ethyl cellulose, gelatine, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hypromellose, magnesium aluminium silicate, maltodextrin, methyl cellulose, povidone, starch or combinations thereof.
The sweetener and/or taste-regulating agent that can be used in the effervescent formulations produced by the production method of the present invention and comprising miglitol and metformin as the active agent can be selected from a group comprising acesulphame, aspartame, dextrose, fructose, maltitol, maltose, mannitol, saccharin, saccharin sodium, sodium cyclamate, sorbitol, sucralose, sucrose, xylitol, sodium chloride or combinations thereof.
The flavouring agent that can be used in the effervescent formulations produced by the production method of the present invention and comprising miglitol and metformin as the active agent can be selected from menthol, lemon, orange, vanilla, strawberry, raspberry, caramel and similar flavours or combinations thereof. Another characteristic feature of the formulations produced by the production method of the present invention is that said formulations comprise miglitol and metformin as the active agent and their tablet hardness value is in the range of 3 kP to 50 kP.
Another characteristic feature of the formulations produced by the production method of the present invention is that said formulations comprise miglitol and metformin as the active agent and their tablet hardness value is in the range of 4 kP to 40 kP.
Another characteristic feature of the formulations produced by the production method of the present invention is that said formulations comprise miglitol and metformin as the active agent and their tablet hardness value is in the range of 5 kP to 30 kP. As a result of the studies conducted in the scope of the present invention, it has been found that the most excellent mechanical tablet resistance and the most suitable dissolution rate and therefore the highest bioavailability are obtained with the formulations having a tablet hardness value in the range of 3 kP to 50 kP.
The examples of the formulations of the present invention are given below. Said examples are given in order to make the invention more comprehensible though the present invention should not be limited to these examples.
EXAMPLE 1: Effervescent formulation comprising the combination of miglitol and metformin and production method
Figure imgf000006_0001
The first granulation: The granulation solution comprising the granulation solvent and the binder is prepared. The mixture obtained by mixing the effervescent acid, the effervescent base and the binder is granulated with the granulation solution; the granules are dried and sieved.
The second granulation: The granulation solution comprising the granulation solvent and the sweetener is prepared. Metformin is granulated with this granulation solution. The granules are dried and sieved.
The granules obtained by the first and the second granulation processes are mixed with miglitol, the lubricant and the flavouring agent and compressed in tablet dosage form.

Claims

1. A method that shall be used in production of effervescent formulations comprising the combination of miglitol and metformin as the active agent, characterized in that said method is composed of the steps of:
• Granulating the mixture comprising at least one effervescent acid, at least one effervescent base and at least one pharmaceutically acceptable excipient with the granulation solution comprising a granulation solvent and optionally one or more excipients and drying them,
• Granulating metformin with the granulation solution comprising the granulation solvent and optionally one or more excipients, drying them and
• Mixing miglitol and at least one excipient with the granules obtained in the first two steps.
2. The production method according to claim 1, characterized in that said method is composed of the steps of:
I. Preparing a granulation solution comprising the granulation solvent and optionally one or more excipients,
II. Mixing at least one effervescent acid, at least one effervescent base and at least one excipient,
III. Granulating the mixture obtained in the IInd step with the granulation solution prepared in the Ist step,
rV. Drying the granules,
V. Preparing a granulation solution comprising the granulation solvent and optionally one or more excipients,
VI. Granulating metformin with the granulation solution prepared in the Vth step,
VII. Drying the granules,
VIII. Adding miglitol and at least one excipient into the granules obtained in the IVth and VIIth steps and mixing them,
IX. Compressing the formulation obtained in tablet dosage form.
3. The production method according to claims 1-2, characterized in that the granulation solvent is selected from water, ethanol, methanol, acetone, ethyl acetate, hexane, heptane, n-octane n-butyl acetate, propanol, t-butyl alcohol, dichloromethane or aqueous HCI solution, aqueous NaOH solution or a combination thereof.
4. The production method according to claims 1-3, characterized in that the effervescent acid used in the granulation is selected from a group comprising malic acid, citric acid, tartaric acid, fumaric acid or combinations thereof.
5. The production method according to claims 1-3, characterized in that the effervescent base used in the granulation is selected from a group comprising sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate or combinations thereof.
6. The production method according to claim 2, characterized in that the excipient comprised in the Ist and IInd steps of said production method is a pharmaceutically acceptable binder.
7. The production method according to claim 6, characterized in that the binders comprised in the Ist and IInd steps of said production method are identical to each other.
8. The production method according to claim 6, characterized in that the binders comprised in the Ist and IInd steps of said production method are different from each other.
9. The production method according to claim 2, characterized in that at least one pharmaceutically acceptable excipient included in the Vth and VIIIth steps of the production method is selected from a group comprising binder, lubricant, sweetener, flavouring agent.
10. The production method according to claim 9, characterized in that the binder is selected from a group comprising carboxymethyl cellulose sodium, ethyl cellulose, gelatine, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hypromellose, magnesium aluminium silicate, maltodextrin, methyl cellulose, povidone, starch or combinations thereof.
11. The production method according to claim 9, characterized in that the lubricant is selected from a group comprising calcium stearate, magnesium stearate, polyethylene glycol, sodium benzoate, potassium benzoate, sodium lauryl sulphate, talc, stearic acid, zinc stearate or combinations thereof.
12. The production method according to claim 9, characterized in that the sweetener and/or taste regulating agent is selected from a group comprising acesulphame, aspartame, dextrose, fructose, maltitol, maltose, mannitol, saccharine, saccharine sodium, sodium cyclamate, sorbitol, sucralose, sucrose, xylitol, sodium chloride or combinations thereof.
13. The production method according to claim 9, characterized in that the flavouring agent is selected from menthol, lemon, orange, vanilla, strawberry, raspberry, caramel and similar flavours or combinations thereof.
14. A formulation produced by the production method according to any preceding claims, characterized in that said formulation comprises miglitol in the range of 1-80% in proportion to unit dosage weight.
15. The formulation produced by the production method according to claim 14, characterized in that said formulation comprises miglitol in the range of 1 - 70% in proportion to unit dosage weight.
16. The formulation produced by the production method according to claims 14-15, characterized in that said formulation comprises miglitol in the range of 1 - 50% in proportion to unit dosage weight.
17. The formulation produced by the production method according to any preceding claims, characterized in that said formulation comprises metformin in the range of 1 - 80% in proportion to unit dosage weight.
18. The formulation produced by the production method according to claim 17, characterized in that said formulation comprises metformin in the range of 1 - 70% in proportion to unit dosage weight.
19. The formulation produced by the production method according to claims 17-18, characterized in that said formulation comprises metformin in the range of 1 - 50% in proportion to unit dosage weight.
20. The formulation according to claims 14-19, characterized in that the ratio of miglitol to metformin comprised in said formulation is in the range of 0.01 -8 by weight.
21. The formulation according to claim 20, characterized in that the ratio of miglitol to metformin is in the range of 0.03-5 by weight.
22. The formulation according to claims 20-21, characterized in that the ratio of miglitol to metformin is in the range of 0.05-1 by weight.
23. An effervescent formulation comprising miglitol and metformin as the active agent, characterized in that tablet hardness value of said formulation is in the range of 3 to 50 kP.
24. The effervescent formulation according to claim 23, characterized in that tablet hardness value of said formulation is in the range of 4 to 40 kP.
25. The effervescent formulation according to claims 23-24, characterized in that tablet hardness value of said formulation is in the range of 5 to 30 kP.
PCT/TR2013/000055 2012-01-31 2013-01-31 A production method for (effervescent) pharmaceutical compositions comprising an alpha - glucosidase inhibitor (miglitol) and metformin Ceased WO2013115746A1 (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
TR2012/01094 2012-01-31
TR201201094 2012-01-31
TR201203399 2012-03-26
TR2012/03399 2012-03-26

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PCT/TR2013/000053 Ceased WO2013115744A1 (en) 2012-01-31 2013-01-31 A process for production of pharmaceutical (effervescent) composition comprising alpha - glucosidase inhibitor (e.g. vogliobose and metformin)
PCT/TR2013/000055 Ceased WO2013115746A1 (en) 2012-01-31 2013-01-31 A production method for (effervescent) pharmaceutical compositions comprising an alpha - glucosidase inhibitor (miglitol) and metformin

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