Classifications

• • 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
• • 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)

Definitions

• the present invention relates to pharmaceutical formulations comprising voglibose and metformin that shall be used in the treatment of diabetes.
• Voglibose was first disclosed in the application numbered EP0056194 (Bl).
• the a-glucosidase inhibitor voglibose is effective in slowing carbohydrate metabolism, in removing hyperglycaemic symptoms and in the treatment of patients with metabolic disorders and it has a role in prevention of high blood sugar level and it is used in the treatment of diabetes.
• Metformin on the other hand, was first disclosed in the application numbered US3174901 (A). In said document, it was disclosed that metformin is effective in the treatment of diabetes.
• Metformin is available in 500, 850, 1000 mg film coated tablet forms on the market.
• an alpha glucosidase inhibitor voglibose prevents digestion of polysaccharides and due to undigested polysaccharides in the intestine, flatulence, diarrhea and similar digestive system complaints are frequently observed in the patients.
• the present invention relates to effervescent tablet formulations comprising voglibose and metformin hydrochloride as the active agent.
• the present invention relates to effervescent formulations comprising voglibose-metformin hydrochloride combination, effervescent couple comprising at least one effervescent acid and at least one effervescent base and at least one pharmaceutically acceptable excipient.
• the present invention relates to selection of effervescent acid and base constituting the effervescent couple from a specific group of substances for the effervescent tablet formulations comprising voglibose-metformin hydrochloride combination.
• At least one pharmaceutically acceptable effervescent acid that can be used in said voglibose- metformin hydrochloride formulations is selected from a group comprising organic acids such as malic acid, citric acid, tartaric acid, fumaric acid.
• physico-chemical parameters such as tablet dispersion time and tablet hardness vary according to the excipients and their amounts used in the effervescent tablet formulations.
• the dosage forms obtained may crumble quickly and be broken during packaging, storing and carrying.
• Hard tablets on the other hand, take long to dissolve. Long dissolution time is an important problem especially for formulations in effervescent form.
• the effervescent couple comprising citric acid as the effervescent acid and an effervescent base selected from a specific group of effervescent bases provides said physico-chemical characteristics.
• the present invention relates to effervescent tablet formulations comprising voglibose-metformin hydrochloride combination and effervescent couple that is composed of citric acid as the effervescent acid and an effervescent base selected from a specific group of effervescent bases.
• At least one pharmaceutically acceptable effervescent base that can be used in said voglibose- metformin hydrochloride formulations is selected from a group comprising sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate.
• the effervescent base is preferably selected from bicarbonates; preferably it is potassium hydrogen carbonate.
• the inventors have obtained ideal tablet dispersion time and hardness by using citric acid in the range of 30 to 55%, preferably in the range of 35 to 50% in proportion to weight of unit formulation in the effervescent tablet formulations comprising voglibose-metformin hydrochloride combination.
• a characteristic feature of the present invention relates to effervescent tablet formulations comprising voglibose-metformin hydrochloride combination wherein citric acid is used in the range of 30 to 55%, preferably in the range of 35 to 50% in proportion to weight of unit formulation.
• the moisture ratio of citric acid that shall be used in the formulations of the present invention varies in the range of 0.01% to 0.3%, preferably in the range of 0.05 to 01%.
• the hardness of the tablets obtained from said formulations varies in the range of 3 to 15 kP, preferably in the range of 5 to 10 kP. It was observed that effervescent tablets comprising voglibose and metformin hydrochloride having said hardness value are durable under abrasive conditions such as carrying, production, etc. as well as they can disperse in a short time.
• the inventors have obtained a pharmaceutical mixture that can remain homogeneous during production and also disperse in a short time, for instance in less than 5 minutes by using effervescent acid having a specific particle size in said effervescent tablet formulations.
• citric acid having a dso value in the range of 100 to 250 ⁇ , preferably in the range of 150 to 200 ⁇ and a d9 0 value in the range of 280 to 380 ⁇ , preferably in the range of 300 to 350 ⁇ has a positive effect on dispersion of the formulation.
• d 5 o signifies that half of the said substance by volume has a particle size over the value stated with d 50 and other half of the substance has a particle size below the value stated with d5o.
• d ⁇ signifies that 90% of the said substance by volume has a particle size below the value stated with dgo and 10% of the substance has a particle size over the value stated with d 0.
• D50 and dgs values can be measured with one of the known measuring devices, for instance with a device which measures particle distribution by laser diffraction (for instance, Malvern Mastersizer etc.).
• the present invention relates to effervescent tablet formulations comprising voglibose-metformin hydrochloride combination, wherein citric acid having a d 5 o value in the range of 100 to 250 ⁇ , preferably in the range of 150 to 200 ⁇ and a dcio value in the range of 280 to 380 ⁇ , preferably in the range of 300 to 350 ⁇ and a moisture ratio in the range of 0.01% to 0.3%, preferably in the range of 0.05% to 0.1%, is used in the range of 30 to 55%, preferably in the range of 35 to 50% in proportion to total weight of unit formulation.
• the ratio of the effervescent base to citric acid constituting the effervescent couple is in the range of 1:1 to 1 :3, preferably in the range of 1:1.5 to 1 :2.
• At least one pharmaceutically acceptable excipient that can be used in addition to effervescent couple in voglibose-metformin formulations of the present invention can be selected from a group comprising diluent, binder, lubricant, flavouring agent and glidant.
• the diluent that can be used in said formulations is selected from a group comprising calcium carbonate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulphate, microcrystalline cellulose, dextrose, fructose, lactitol, lactose, magnesium carbonate, magnesium oxide, maltitol, maltodextrin, maltose, mannitol, simethicone, sorbitol, starch, sodium chloride, sucrose, talc, xylitol.
• the binder that can be used in said formulations can be selected from a group comprising carboxymethyl cellulose sodium, ethyl cellulose, gelatine, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hypromellose, magnesium aluminium silicate, maltodextrin, methylcellulose, povidone, starch.
• the lubricant that can be used in said formulations 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.
• the flavouring agent that can be used in said formulations can be selected from blackberry, menthol, lemon, orange, vanilla, strawberry, raspberry, caramel and similar flavours.
• the glidant that can be used in said formulations is selected from a group comprising tribasic calcium phosphate, colloidal silicone dioxide, magnesium silicate, magnesium trisilicate, talc.
• the formulations of the present invention are preferably prepared by wet granulation method.
• wet granulation method two active agents are mixed with the excipients for a length of time.
• the mixture obtained is granulated with the granulation solution and the granules are dried. After this phase, the diluent and the lubricant are added and mixed again.
• the mixture obtained is compressed in tablet form and packaged.
• Example 1 Formulation for Preparation of Effervescent Tablets Comprising Voglibose and Metformin.
• excipients 3.490 The formulation given above is prepared by wet granulation method. Firstly, the effervescent couple and the active agents are mixed. The granulation solution comprising at least one excipient and water is added into this solution. The mixture obtained is dried. The granules obtained are sieved and mixed with the other excipients. In the last step, tablet compression and packaging processes are realized.
• Example 2 Formulation for Preparation of Effervescent Sachets Comprising Voglibose and Metformin.
• the formulation given above is prepared by wet granulation method. Firstly, the effervescent couple and active agents are mixed. The granulation solution comprising at least one excipient and water is added into this mixture. The mixture obtained is dried. The granules obtained are sieved and mixed with the other excipients. The formulation obtained is filled into sachets.

Landscapes

• Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Epidemiology (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Engineering & Computer Science (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
• Medicinal Preparation (AREA)

Priority Applications (1)

Applications Claiming Priority (2)

Publications (1)

Family

ID=48048164

Family Applications (1)

Country Status (2)

Cited By (3)

Citations (6)

• 2013
  • 2013-01-31 WO PCT/TR2013/000052 patent/WO2013115743A1/fr not_active Ceased
  • 2013-01-31 EP EP13714364.0A patent/EP2809311A1/fr not_active Withdrawn

Patent Citations (6)

Also Published As

Similar Documents

Legal Events