WO2013115738A1 - Acarbose micronisée - Google Patents

Acarbose micronisée Download PDF

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Publication number
WO2013115738A1
WO2013115738A1 PCT/TR2013/000047 TR2013000047W WO2013115738A1 WO 2013115738 A1 WO2013115738 A1 WO 2013115738A1 TR 2013000047 W TR2013000047 W TR 2013000047W WO 2013115738 A1 WO2013115738 A1 WO 2013115738A1
Authority
WO
WIPO (PCT)
Prior art keywords
acarbose
pharmaceutical composition
μπι
composition
agent
Prior art date
Application number
PCT/TR2013/000047
Other languages
English (en)
Inventor
Mahmut Bilgic
Original Assignee
Mahmut Bilgic
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Mahmut Bilgic filed Critical Mahmut Bilgic
Publication of WO2013115738A1 publication Critical patent/WO2013115738A1/fr

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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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
    • 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

Definitions

  • the present invention relates to pharmaceutical compositions comprising acarbose so as to be used in the treatment of diabetes and non-insulin-dependent diabetes (type II diabetes).
  • Acarbose was first disclosed in the application numbered DE2347782. In said document, it was disclosed that use of acarbose is effective in the treatment of hyperglycemia.
  • Acarbose is available in 25 mg, 50 mg and 100 mg tablet forms on the market.
  • Bioavailability characteristics of the products taken by the oral route are closely related with their dissolutions.
  • the active agent cannot reach to therapeutic amounts since it does not dissolve adequately in body and this influences the treatment process negatively.
  • compositions should have content uniformity; in other words, comprise equal amounts of active agent per unit dose when they are formed into various dosage forms. This depends on flow characteristics of the formulations prepared. Formulations having the desired flow characteristics comprise equal amount of active agent per unit dose.
  • the inventors have found that the pharmaceutical compositions comprising acarbose having an average particle size (d 50 ) equal to or smaller than 15 ⁇ have better dissolution and content uniformity could easily be provided during preparation of the dosage forms of the pharmaceutical compositions comprising acarbose having an average particle size (d 5 o) equal to or smaller than 15 ⁇ .
  • the present invention relates to pharmaceutical compositions comprising acarbose having an average particle size (d 5 o) equal to or smaller than 15 ⁇ .
  • acarbose having an average particle size (dw) preferably in the range of 1 ⁇ to 15 ⁇ , more preferably in the range of 3 ⁇ to 12 ⁇ is used in the formulations of the present invention.
  • the term d 50 signifies that half of the said substance by volume has a particle size over the value stated with dso and the other half of the substance by volume has a particle size below the value stated with d 50 .
  • Acarbose comprised in the pharmaceutical compositions of the present invention can be in the form of its pharmaceutically acceptable salts, hydrates, solvates, esters, enantiomers, diastereomers or combinations thereof.
  • D 5 o value 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.).
  • Acarbose of the present invention having a d 50 value equal to or smaller than 15 ⁇ can be used after bought as a product which is commercially provided in this form. Furthermore, acarbose having a d 50 value equal to or smaller than 15 ⁇ can also be obtained by pulverizing a product having coarser particle size singly or with an excipient (for instance microcrystalline cellulose etc.). At this point, pulverization can be performed by using the methods of impact mill, jet mill, blade mill etc. Pulverization can be performed before preparation of the pharmaceutical composition comprising acarbose as well as during preparation of the pharmaceutical composition of the present invention or before post-production storage of the pharmaceutical composition prepared.
  • pulverization is performed by the effect of rotating blades in the device.
  • pulverization is performed by the effect of rotating hammers in the device.
  • pulverization is performed by providing collision of the particles with each other with the help of high-pressured and high-speed airstream.
  • compositions of the present invention comprising acarbose having a d 5 o value equal to or smaller than 15 ⁇ can be prepared in the form of any of the dosage forms such as tablet, effervescent tablet, effervescent granule, effervescent dry powder, film coated tablet, enterically coated tablet, dry powder, granule, capsule, prolonged release tablet, modified release tablet, delayed release tablet.
  • the tablets obtained can be treated with film coating agents, for instance with sugar based coating agents, water soluble film coating agents, enteric coating agents, delayed release coating agents or with coating compositions comprising any combination thereof.
  • Saccharose can be used singly or optionally with any of the agents such as talc, calcium carbonate, calcium phosphate, calcium sulphate, gelatine, gum arabic, polyvinylpyrrolidone and pullulan or a combination thereof as the sugar based coating agent.
  • the water soluble film coating agent can be selected from cellulose derivatives such as hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, methyl hydroxyethyl cellulose and sodium carboxymethyl cellulose; synthetic polymers such as polyvinyl acetal diethyl aminoacetate, aminoalkyl methacrylate copolymers and polyvinylpyrrolidone and polysaccharides such as pullulan or combinations thereof.
  • cellulose derivatives such as hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, methyl hydroxyethyl cellulose and sodium carboxymethyl cellulose
  • synthetic polymers such as polyvinyl acetal diethyl aminoacetate, aminoalkyl methacrylate copolymers and polyvinylpyrrolidone and polysaccharides such as pullulan or combinations thereof.
  • the enteric coating agents can be selected from cellulose derivatives such as hydroxypropyl methyl cellulose phthalate, hydroxypropyl methyl cellulose acetate succinate, carboxymethyl ethyl cellulose, cellulose acetate phthalate; acrylic acid derivatives such as methacrylic acid copolymer L, methacrylic acid copolymer LD and methacrylic acid copolymer S and natural substances such as shellac or combinations thereof.
  • cellulose derivatives such as hydroxypropyl methyl cellulose phthalate, hydroxypropyl methyl cellulose acetate succinate, carboxymethyl ethyl cellulose, cellulose acetate phthalate
  • acrylic acid derivatives such as methacrylic acid copolymer L, methacrylic acid copolymer LD and methacrylic acid copolymer S and natural substances such as shellac or combinations thereof.
  • the delayed release coating agents can be selected from cellulose derivatives such as ethyl cellulose; acrylic acid derivatives such as aminoalkyl methacrylate copolymer RS, emulsion copolymer of ethyl acrylate-methyl methacrylate or combinations thereof.
  • compositions of the present invention can comprise various excipients in addition to the active agent acarbose.
  • compositions of the present invention comprise at least one excipient selected from a group comprising disintegrant, diluent, lubricant, glidant, binder, effervescent couple comprising at least one acidic agent and at least one basic agent, coloring agent, pH regulating agent, surfactant, stabilizing agent, sweetener and/or taste regulating agent, flavoring agent in addition to the active agent acarbose.
  • excipient selected from a group comprising disintegrant, diluent, lubricant, glidant, binder, effervescent couple comprising at least one acidic agent and at least one basic agent, coloring agent, pH regulating agent, surfactant, stabilizing agent, sweetener and/or taste regulating agent, flavoring agent in addition to the active agent acarbose.
  • the disintegrant that can be used in the pharmaceutical compositions of the present invention can be selected from a group comprising carboxymethyl cellulose, carboxymethyl cellulose calcium, carboxymethyl cellulose sodium, croscarmellose sodium, crospovidone, hydroxypropyl cellulose, microcrystalline cellulose, methyl cellulose, chitosan, starch, sodium starch glycolate.
  • the diluent that can be used in the pharmaceutical compositions of the present invention can be 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 lubricant that can be used in the pharmaceutical compositions of the present invention 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 glidant that can be used in the pharmaceutical compositions of the present invention can be selected from a group comprising tribasic calcium phosphate, colloidal silicone dioxide, magnesium silicate, magnesium trisilicate, talc.
  • the binder that can be used in the pharmaceutical compositions of the present invention 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.
  • the acidic agent composing the effervescent couple comprising at least one acidic agent and at least one basic agent that can be used in the pharmaceutical compositions of the present invention can be selected from a group comprising organic acids such as malic acid, citric acid, tartaric acid, fumaric acid; and the basic agent can be selected from a group comprising agents such as sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate.
  • the pH regulating agent that can be used in the pharmaceutical compositions of the present invention can be selected from citrate, phosphate, carbonate, tartrate, fumarate, acetate and amino acid salts.
  • the surfactant that can be used in the pharmaceutical compositions of the present invention can be selected from sodium lauryl sulphate, polysorbate, polyoxyethylene, polyoxypropylene glycol and similar agents.
  • the stabilizing agent that can be used in the pharmaceutical compositions of the present invention can be selected from a group comprising tocopherol, tetrasodium edetate, nicotinamide, cyclodextrin.
  • the sweetener and/or taste regulating agent that can be used in the pharmaceutical compositions of the present invention can be selected from a group comprising acesulfame, aspartame, dextrose, fructose, maltitol, maltose, mannitol, saccharine, saccharine sodium, sodium cyclamate, sorbitol, sucralose, sucrose, xylitol, sodium chloride.
  • the flavoring agent that can be used in the pharmaceutical compositions of the present invention can be selected from a group comprising menthol, lemon, orange, vanilla, berry, raspberry, caramel and similar flavors.
  • compositions of the present invention comprise acarbose in the range of 0.1% to 100% by weight, preferably in the range of 1% to 99% by weight, more preferably in the range of 5% to 95% by weight.
  • the present invention relates to the pharmaceutical compositions comprising acarbose having a d 90 value equal to or smaller than 50 ⁇ .
  • the inventors have seen that the active agent and the excipients are mixed homogeneously during preparation of the pharmaceutical compositions comprising acarbose having a d 9 o value equal to or smaller than 50 ⁇ and each unit dosage form prepared with the formulation obtained with acarbose having said characteristics comprises equal amount of the active agent as a result.
  • the present invention relates to pharmaceutical compositions comprising acarbose having a d 90 value equal to or smaller than 50 ⁇ .
  • D 90 value of acarbose comprised in the pharmaceutical compositions of the present invention is equal to or smaller than 50 ⁇ , preferably in the range of 1 ⁇ to 50 ⁇ , more preferably in the range of 5 ⁇ to 45 ⁇ .
  • the present invention relates to the pharmaceutical compositions comprising acarbose having a d 5 o value equal to or smaller than 15 ⁇ and a d 9 o value equal to or smaller than 50 ⁇ .
  • the present invention relates to the pharmaceutical compositions comprising acarbose having a d 5 o value in the range of 1 ⁇ to 15 ⁇ and a dgo value in the range of 1 ⁇ to 50 ⁇ .
  • the present invention relates to the pharmaceutical compositions comprising acarbose having a d 5 o value in the range of 3 ⁇ to 12 ⁇ and a d 9 o value in the range of 5 ⁇ to 45 ⁇ .
  • the present invention relates to the pharmaceutical compositions comprising acarbose having a d 50 value in the range of 3 ⁇ to 12 ⁇ and a de value in the range of 15 ⁇ to 40 ⁇ .
  • d 9 o signifies that 90% of the said substance by volume has a particle size below the stated value and 10% of the said substance by volume has a particle size over the stated value.
  • compositions of the present invention comprising acarbose having a d 5 o value equal to or smaller than 15 ⁇ can optionally comprise a second active agent in addition to acarbose.
  • the second active agent can be selected from antacid, anticholinergic, antispasmodic, antiemetic, antibiotic, antipropulsive, antiallergic, antidiarrheal, antiobesity, antithrombotic, antifibrinolytic, antianemic, antihypertensive, antifungal, antipruritic, antipsoriatic, antibiotic, antiseptic, antiacne, antibacterial, antimycotic, antiviral, antineoplastic, antiarrhythmic, antiadrenergic, antiepileptic, anti- parkinson, antiprotozoal, anthelmintic, anti-inflammatory, diuretic, laxative, sulphonamide, imidazole, corticosteroid, thiazolidinedione, bigu
  • compositions of the present invention comprising acarbose having a d 50 value equal to or smaller than 15 ⁇ can optionally comprise a second active agent in addition to acarbose.
  • the second active agent can be selected from a group comprising meglitinides, alpha-glucosidase inhibitors, sulfonylureas, thiazolidinediones, biguanides, dipeptidyl peptidase-4 inhibitors.
  • said second active agent can be selected from a group comprising agents such as nateglinide, repaglinide belonging to meglitinide group; alpha-glucosidase inhibitors voglibose, miglitol; acetohexamide, glibenclamide, glibornuride, gliclazide, gliquidone, glimepiride, glipizide, chlorpropamide, tolbutamide belonging to sulfonylurea group; pioglitazone, rosiglitazone, rivoglitazone, rosiglitazone maleate, pioglitazone hydrochloride, troglitazone belonging to thiazolidinedione group; phenformin, metformin or a pharmaceutically acceptable salt thereof, for instance metformin hydrochloride belonging to biguanide group; dipeptidyl peptidase-4 inhibitors sitagliptin, vildagliptin, sax
  • composition of the present invention can be obtained by a method composed of the steps of;
  • the pharmaceutical composition of the present invention can be used in the treatment of diabetes and non-insulin-dependent diabetes (type II diabetes), in the treatment of patients suffering metabolic disorders, in slowing down carbohydrate metabolism, in removing hyperglycemic symptoms and in preventing blood sugar increase.
  • type II diabetes non-insulin-dependent diabetes
  • the examples below are given in order to explain the present invention, yet the scope of the invention cannot be limited to these examples.
  • EXAMPLE 1 Tablet formulation comprising acarbose
  • a granulation solution is prepared with at least one excipient.
  • Acarbose is granulated with this granulation solution.
  • the granules obtained are mixed with the lubricant and the other excipients.
  • the formulation prepared can be packed in powder or granule form as well as compressed into tablets.
  • EXAMPLE 2 Film tablet formulation comprising acarbose
  • EXAMPLE 3 Effervescent tablet formulation comprising acarbose
  • Acarbose and the excipients are mixed. Effervescent couple is added to the mixture obtained and granulated. The granules are dried and mixed with the other excipients. The lubricant is added to the final mixture and the pharmaceutical composition obtained is compressed into tablets in the tablet compression machine.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention concerne des compositions pharmaceutiques contenant de l'acarbose, qui sont destinées au traitement du diabète et du diabète non insulinodépendant (diabète de type II).
PCT/TR2013/000047 2012-01-31 2013-01-31 Acarbose micronisée WO2013115738A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
TR201201097 2012-01-31
TR2012/01097 2012-01-31

Publications (1)

Publication Number Publication Date
WO2013115738A1 true WO2013115738A1 (fr) 2013-08-08

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Application Number Title Priority Date Filing Date
PCT/TR2013/000047 WO2013115738A1 (fr) 2012-01-31 2013-01-31 Acarbose micronisée

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WO (1) WO2013115738A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104523653A (zh) * 2015-02-06 2015-04-22 杭州朱养心药业有限公司 阿卡波糖胶囊剂药物组合物
CN104546795A (zh) * 2015-02-06 2015-04-29 杭州朱养心药业有限公司 阿卡波糖胶囊剂和制法
CN116236451A (zh) * 2023-04-18 2023-06-09 淄博市中心医院 一种阿卡波糖片、制备方法及用途

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2347782A1 (de) 1973-09-22 1975-04-10 Bayer Ag Aminozuckerderivate, verfahren zu ihrer herstellung, sowie ihre verwendung als arzneimittel
WO2003077825A2 (fr) * 2002-03-12 2003-09-25 Microdose Technologies, Inc. Administration a specificite de site de medicaments pris simultanement par inhalation
WO2009135951A2 (fr) * 2008-05-09 2009-11-12 Atacama Labs Oy Procédé pour préparer un comprimé contenant de la metformine
WO2011134962A2 (fr) * 2010-04-27 2011-11-03 Bayer Pharma Aktiengesellschaft Comprimé à désintégration orale contenant de l'acarbose

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2347782A1 (de) 1973-09-22 1975-04-10 Bayer Ag Aminozuckerderivate, verfahren zu ihrer herstellung, sowie ihre verwendung als arzneimittel
WO2003077825A2 (fr) * 2002-03-12 2003-09-25 Microdose Technologies, Inc. Administration a specificite de site de medicaments pris simultanement par inhalation
WO2009135951A2 (fr) * 2008-05-09 2009-11-12 Atacama Labs Oy Procédé pour préparer un comprimé contenant de la metformine
WO2011134962A2 (fr) * 2010-04-27 2011-11-03 Bayer Pharma Aktiengesellschaft Comprimé à désintégration orale contenant de l'acarbose

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104523653A (zh) * 2015-02-06 2015-04-22 杭州朱养心药业有限公司 阿卡波糖胶囊剂药物组合物
CN104546795A (zh) * 2015-02-06 2015-04-29 杭州朱养心药业有限公司 阿卡波糖胶囊剂和制法
CN116236451A (zh) * 2023-04-18 2023-06-09 淄博市中心医院 一种阿卡波糖片、制备方法及用途
CN116236451B (zh) * 2023-04-18 2024-04-19 淄博市中心医院 一种阿卡波糖片、制备方法及用途

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