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WO2016042567A1 - Extended release formulation of metformin - Google Patents

Extended release formulation of metformin Download PDF

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Publication number
WO2016042567A1
WO2016042567A1 PCT/IN2014/000602 IN2014000602W WO2016042567A1 WO 2016042567 A1 WO2016042567 A1 WO 2016042567A1 IN 2014000602 W IN2014000602 W IN 2014000602W WO 2016042567 A1 WO2016042567 A1 WO 2016042567A1
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WIPO (PCT)
Prior art keywords
metformin
instamodel
pharmaceutical composition
solid pharmaceutical
release
Prior art date
Application number
PCT/IN2014/000602
Other languages
French (fr)
Inventor
Suresh Pareek
Original Assignee
Suresh Pareek
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
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Priority to PCT/IN2014/000602 priority Critical patent/WO2016042567A1/en
Publication of WO2016042567A1 publication Critical patent/WO2016042567A1/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/20Pills, tablets, discs, rods
    • A61K9/2004Excipients; Inactive ingredients
    • A61K9/2022Organic macromolecular compounds
    • A61K9/205Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/13Amines
    • A61K31/155Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)

Definitions

  • WO 201 1060256, WO 2003039527 and WO 2005123134 disclose the use of hydrophilic polymers like hypromellose for extended release of drug like metformin. These polymers extend the release of drug by showing osmosis nature in aqueous conditions.
  • Cellulosic matrix based system work by the swelling and gelling function i.e. these polymer swell through influx of liquids and a gel like physical structure is formed which provides extended release effect facilitated by diffusion of the Metformin.
  • Some patents that disclose matrix based systems for slow release of metformin include WO 20071 361 5 1 and US 5955 1 06.
  • Metformin is blended with the ready to use polymer and aqueous granulated further the granulated mixture is compressed to produce a solid formulation.
  • the ingredients are blended to form a uniform powder and then compressed with means generally known to skilled in the art.
  • Metformin and INSTAMODEL are blended together with binding agent and thereafter wet granulated and dried. These dried granules are then processed in presence o f lubricant and gl idant, and thereafter compressed to form appropriate dosage form and optionally coated .

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  • 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)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

The present invention relates to a dry ready to use modified release dosage formulation for Metformin dosage forms and its salts and derivatives thereof, a process for preparing extended release tablet using INSTAMODEL (A43D00041 and A43 D00042) manufactured by Ideal Cures Private Limited Mumbai India thereof also use thereof as additive to animal feeds, foods and food supplements and also cosmetic and pharmaceutical compositions. Invention also relates to ready-to-use modified release compositions capable of regulating release of Metformin at various dosage strength, a process for production thereof and also use thereof as formulated pharmaceutical compositions.

Description

Description
EXTENDED RELEASE FORMULATION OF METFORMIN
Technical Field
[ 1 J The present invention relates to a dry ready to use modi fied release dosage formulation for Metformin dosage forms and its salts and derivatives thereof, a process for preparing extended release tablet using JN'STAMODEL (A43 D00041 and
A43D00042) manufactured by Ideal Cures Private Limited Mumbai India thereof also use thereof as additive to animal feeds, foods and food supplements and also cosmetic and pharmaceutical compositions. Invention also relates to ready-to-use modi fied release compositions capable of regulating release of Metformin at various dosage ■strength, a process for production thereof and also use thereof as formulated pharmaceutical compositions.
Background Art
[2] In general Metformin has been widely prescribed for lowering blood glucose in patients with diabetes. However, being a short acting drug, metformin requires nvo or three times-a-day dosing. Adverse events associated with metformin use are often gastrointestinal, e.g. anorexia, nausea, vomiting and occasionally diarrhea, etc. These adverse effects may be partially avoided by reducing the initial and/or ma intenance dose or using an extended-release dosage form.
[ 1 Metformin has intrinsically poor permeabi l ity in the lower portion of the gastroi ntestinal tract, leading to absorption from the upper part o f the tract. I t has very hi gh solubility in water (>300mg/ml at 25°C). These parameters can lead to difficu l ty in providing a sustained release of the drug from a formulation and the concomitant problems associated with controlling the initial burst from such a formu lation. The rate of dissolution of such high solubility drugs may be reduced by embedding the drug in a polymeric matrix or surrounding it with a polymeric barrier membrane through ) which the drug must diffuse lo be released for absorption.
[4] , Metformin is administered through solid dosage ranges from 100 mg to 75 mg daily. In standard doses of 100 ing is taken in daily. Prescription of Metformin recommend that it should be taken wi th meals i f possible and daily. Dosage generally should not exceed 1 00 mg dai ly.
[5] In state of the art modified release compositions are developed to provide relatively constant drug plasma levels and sustained efficacy for longer period of time. In principle aim of extended and modified release composition is to get required therapeutic concentration of the active in the blood stream and mainta in its therapeutic concentration without deviation from strength during spec i fied period .
[6] In state of art various grades of cellulosic polymers are used in the modified release compositions e.g. HPMC polymer. WO 201 1060256, WO 2003039527 and WO 2005123134 disclose the use of hydrophilic polymers like hypromellose for extended release of drug like metformin. These polymers extend the release of drug by showing osmosis nature in aqueous conditions. Cellulosic matrix based system work by the swelling and gelling function i.e. these polymer swell through influx of liquids and a gel like physical structure is formed which provides extended release effect facilitated by diffusion of the Metformin. Some patents that disclose matrix based systems for slow release of metformin include WO 20071 361 5 1 and US 5955 1 06.
In theory it is known that with high viscosity grade polymer after attaining gell ing effect drug release is lower but as time progresses drug release is increased. On the contrary with low viscosity grade polymer after attaining gelling effect drug is released at faster speed due to larger pore sized and concentration of drug decrease as time progresses.
In order to minimize difficulties associated in ratios of polymers, batch to batch variations, formulating, storing and preserving many loose components of differently textured and sized ingredients means have been desired in industry to make ready to use extended release or modified release composition which are convenient to handle.
The object of the present invention is to provide a ready-to-use matrix system and method of preparation for Metformin extended release or modi fied release formulation.
Disclosure of Invention
Summary of Invention
Accordingly, the present invention provides hydrophilic matrix system based ready to use technology for Modified or Extended Release Formulation o f Metformin Hydrochloride using INSTAMODEL (A43 D00041 and A43 D00042) manufactured by Ideal Cures Private Limited Mumbai India.
Accordingly, the present invention also provides method for making ready to use Metformin modified or' extended release formulation, involving steps of aqueous granulation, drying, lubrication and punching of tablets.
In another aspect, present invention also provides Twice a day Metformin table dosage form.
Extended release or modified release tablet formulation can be in the form of single or multilayer tablets, capsule shaped oral dosage form, caplei, granules, disc, pellets, granules in capsule, mini-tablets in oral dosage form and other possible oral dosage form mean thereof.
In yet. another embodiment, the solid oral dosage form can optionally include one or more pharmaceutically acceptable excipients.
The details of one or more embodiments in the practice of the inventions are set forth in the description below. Other features, objects and advantages of the inventions will be apparent from the appended examples and claims.
Detailed Description
Below description specify various scientific terms unless stated with context, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art, to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred methods and materials are described.
Unless stated to the contrary. The feature 'ready-to-use', in the context of the present invention, is taken to mean the property that the composition according to the invention can be used directly for its purposes by the user by simply dispersing it in required quantity of water.
The term 'modified release' is in context of the invention as a way of active drug delivery where the rate of release of the active drug from the composition is not exclusively dependent on the concentration of active drug remain ing in the dosage form and / or the solubility of the active drug in the liquid surrounding the composition, and where the time course with or w ithout respective location of release of active drug from an oral dosage form are chosen to accomplish therapeutic or convenience objecti v es not offered by conventional dosage forms. For the purpose of invention active drug is selected from Aceclofenac, its intermediates and derivatives thereof.
The term 'Aceclofenac' is in context of the invention includes its polymorphic forms, the pharmaceutically acceptable salts, including salts esters and pother chemical derivatives or intermediates etc. The solid pharmaceutical composition comprises Aceclofenac from 1 to 80 w/w % of dosage form.
The term 'dosage', 'solid pharmaceutical composition' may include one or more of tablet, capsule, powder, disc, caplet, granules, pellets, granules in capsule, minitablets, minitablets in capsule, pellets in capsule, sachet and the like. The solid pharmaceutical composition also includes multilayer tablets. The solid pharmaceutical compositions are meant for oral administration.
The term 'tablet' includes pharmaceutical compositions of al l shapes and sizes, whether coated or uncoated.
The . term 'Lubricant' in the context of the present invent ion, is taken to mean that an ingredient added to prevent the adhesion of tablet materials to the punches and dies, reduce inter-particle friction and facil itate the ejection of oral dosage forms from the die cavity, .Lubricant of present invention includes but not l imited to talc, magnesium stearate, stearic acid, sodium stearyl fumarate and there derivatives thereof.
The term 'Glidant' in the context of the present invention, is taken to mean that an ingredient which enhance product flow by reducing inter-particulate friction. Glidant can be used in present invention includes but not limited to silicon di-oxide, colloidal silicon dioxide and there derivatives thereof. It is available under several brand names like AEROSIL® and CAB-O-SIL®.
The term 'Solvent' in the context of the present invention, is taken to mean ingredient that facilitate mixing of components in wet granulation process. Solvent can be used in present invention includes but not limited to Acetone, ethanol, methylene di chloride, isopropyl alcohol, water or their mixture thereof.
The term 'Binder' or 'Binding agent' in the context of the present invention, is taken to mean ingredient that facilitate binding of components in wet granulation process. Solvent can be used in present invention includes but not limited to dextrin and their derivatives, inaltodextrin, polyvinyl polymers, Polyvinyl pyrrol idone K30 (PVP K..30) and there derivatives thereof.
The ready to use polymeric composition Instamodel A43D00045 for extended and modified release formulation was supplied by Ideal Cures Private Limited, Mumbai, www.idealcures.co.in . This product was used to create inventive dosage form having ideal modified release profile for twice a day administration.
According to inventors it was surprisingly found that extended release solid oral dosage form for Aceclofenac can be created with ready to use Instamodel
(A43D00045) system and dosage form have advantageous modified release properties. The ready to. use composition in accordance with present invention comprise INSTAMODEL (A43D00045). In one of the embodiment of present invention Aceclofenac is formulated with ready to use composition lo prepare modi fied release dosage form. In accordance with present invention different sails, derivatives, polymorphs of Aceclofenac could be combined to achieve ready-to-use composition to achieve extended or modified release dosage form.
In a dosage form according to the invention Aceclofenac is blended with the ready to use, polymer and aqueous granulated further the granulated m ixture is compressed to produce a solid formulation. The ingredients are blended to form a uniform powder and then compressed with means generally known to skilled in the art.
In yet another embodiment of present invention Aceclofenac and I N STA MODEL are blended together with binding agent and thereafter wet granulated and dried. These dried granules are then processed in presence of lubricant and gl idant, and thereafter compressed to form appropriate dosage form and final ly coated.
In yet another embodiment of present invention Aceclofenac and INSTAMODEL are blended together with binding agent and thereafter wet granulated and dried. These dried granules are then processed in presence of lubricant and glidant, and thereafter compressed to form appropriate dosage form and optional ly coated.
This system of formulation uses simple and economic polymers hence cost effective to the customer. Another advantage of the present formulation is its robust and reproducible results for extended release dose form without batch to batch variations. Further by using aqueous solvent system for granulation dosage form does not have any residual solvent or hazardous effect found in many organic solvent based formulations.
Inventive dosage form may be prepared by blending Aceclofenac, their derivatives or combination thereof along with ready to use composition. Therefore inventive for- r
mulation preparation comprise steps as:-
Below description specify various scientific terms unless stated with context, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art, to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred methods and materials are described.
Unless stated to the contrary, The feature 'ready-to-use1, in the context of the present invention, is taken to mean the property that the composition according to the invention can be used directly for its purposes by the user by simply dispersing it in required quantity of water.
The term 'modified release' is in context of the invention as a way of active drug delivery where the rate of release of the active drug from the composition is not exclusively dependent on the concentration of active drug remaining in the dosage form and / or the solubility of the active drug in the liquid surrounding the composition, and where the time course with or without respective location of re lease o f act i ve drug from an oral dosage form are chosen to accomplish therapeutic or convenience ob jectives not offered by conventional dosage forms. For the purpose o i' invention active - drug is selected from Metformin, its intermediates and derivati ves thereof.
The term 'Metformin' is in context of the invention includes its polymorphic forms, the pharmaceutically acceptable salts, including salts esters and pother chemical derivatives or intermediates etc. The solid pharmaceutical composi tion comprises Metformin from 1 to 90 w/w % of dosage form.
The term 'dosage', 'solid pharmaceutical composi tion' may include one or more of tablet, capsule, powder, disc, caplet, granules, pellets, granules in capsule, minitablets, minitablets in capsule, pellets in capsule, sachet and the like. The sol id 'pharmaceutical' composition also includes multilayer tablets. T he solid pharmaceutical composi tions are meant for oral administration.
. . The term 'tablet' includes pharmaceutical compositions of all shapes and sizes, whether coated or uncoated.
The term 'Lubricant' in the context of the present invention, is taken to mean that an ingredient added to prevent the adhesion of tablet materials to the punches and dies, reduce inter-particle friction and facilitate the ejection of oral dosage forms from the die cavity. Lubricant of present invention includes but not limited to talc, magnesium stearate, stearic acid, sodium stearyl fumarate and there derivatives thereof.
The term 'Glidant' in the context of the present invention, is taken to mean that an ingredient which enhance product flow by reducing inter-particulate friction. G l idant can be used in present invention includes but not limited to sil icon di-oxide, colloida l silicon dioxide and there derivatives thereof. It is available under several brand names like AEROS1L® and CAB-O-SIL®. The term 'Solvent' in the context of the present invention, is taken to mean ingredient that facilitate mixing of components in wet granulation process. Solvent can be used in present invention includes but not limited to Acetone, ethanol, methylene di chloride, isopropyl alcohol, water or their mixture thereof.
The term 'Binder' or 'Binding agent' in the context of the present invention, is taken to mean ingredient that facilitate binding of components in wet granulation process. Solvent can be used in present invention includes but not l imited to dextrin and their derivatives, maltodextrin, polyvinyl polymers, Polyvinyl pyrrol idone 30 (PVP .30) and there derivatives thereof.
The ready to use polymeric composition Instamodel A43D0004 1 and A43 D00042 for extended and modified release formulation was supplied by Idea l Cures Private Limited, Mumbai, www.idealcures.co. in . This product was used to create inventive dosage form having ideal modified release profi le for Once a day administration.
According lo inventors it was surprisingly found that extended release solid oral dosage form for Metformin can be created with ready to use I nstamodel (A4 D0004 f and A43D00042) system and dosage form have advantageous modi fied release properties, The ready to use composition in accordance with present invention comprise INSTAMODEL (A43D00041 and A43 D00042 ). Instamodel blends combination can be used in plurality of layers and combinations including but not limited to various combinations and orders of mixings or granulations. In one of the embodiment of present invention Metformin is formulated with ready lo use composition ; to prepare modified release dosage form. In yet another embodiment metformin is formulated with ready to use composition with different grades and orders of mi xing and granulations. In accordance with present invention different salts, derivat i ves, polymorphs of Metformin could be combined to achieve ready-to-use composit ion to achieve extended or modified release dosage form.
In a dosage form according to the invention Metformin is blended with the ready to use polymer and aqueous granulated further the granulated mixture is compressed to produce a solid formulation. The ingredients are blended to form a uniform powder and then compressed with means generally known to skilled in the art.
In yet another embodiment of present invention Metformin and INSTAMODEL are blended together with binding agent and thereafter wet granulated and dried. These dried granules are then processed in presence of lubricant and glidant, and thereafter compressed; to form appropriate dosage form and finally coated.
In yet another embodiment of present invention Metformin and INSTAMODEL are blended together with binding agent and thereafter wet granulated and dried. These dried granules are then processed in presence o f lubricant and gl idant, and thereafter compressed to form appropriate dosage form and optionally coated .
This system of formulation uses simple and economic polymers hence cost effective to the customer. Another advantage of the present formulation is its robust and reproducible results for extended release" dose form without batch to batch variations. Further by using aqueous solvent system for granulation dosage form does not have any residual solvent or hazardous effect found in many organic solvent based formulations.
Inventive dosage form may be prepared by blending Metformin, their deri vati ves or combination thereof along with ready to use composition. Therefore inventi ve formulation preparation comprise steps as:-
1 . Blending of ready to use formulation Instamodel (A43 D00041 ) with
Metformin.
2. Thorough mixing to form dry powder
3. Wet granulation with active drug and solvent
4. Sieving through appropriate size
5. Tray drying or fluidized bed drying
6. Again blending with ready to use formulation instamodel (A43 D00042)
7. Optionally addition of lubricant
S. Final tablet compression
9. Optional film coating- According to one of the embodiment inventive dosage form is prepared by blending ready to use composition ( Instamodel A43D00041 and A43 D00042 ), process blending is performed by conventional dry blender or a food processor or 'V -blender1 or a similar function device. Further Metformin are processed us ing aqueous solvent with binder through wet granulation or a similar wet mixing method to generate dosage formulation. Dosage formulation is further dried, sieved and compressed op- . tionally with addition of lubricant, binder, glidant to form modified release oral, dosage form.
In one of the embodiment of present invention, inventive dosage formulations are prepared by blending Metformin along with Instamodel (A43D0004 1 and
A43D00042). Initially all components are blended by conventional dry blending in a food processor or 'V-blender' or a similar function device. Other solid oral dosage formulation components like binders, lubricants, glidants, detackifier,. excipients can be added to create inventive formulation. Further mixture is then processed with appropriate quantity of aqueous solvent with binder and wet granulated. Obtained sieved granulated is then uniformly mixed with premeasured amount of the lubricant to improve industrial acceptability and oral dosage compression quality. Subsequently uniform mixed inventive formulation is compressed in standard pharmacopoeial equipment to get a controlled release oral dosage formulation of the correct desired weight and strength.
In yet another embodiment Metformin is formulated comprising steps of mixing Instamodel with Metformin with solvents, granulating and drying to granulation which is subsequently sifted using appropriate mesh screen. Further generated granules can be again blended with instamodel to generate plurality of layers. Finally generated granules are sifted and blended with lubricants.
According to one of the main embodiment wherein hardness of tablets produced is in range of 5 Kg/cm2 to 30 Kg/cm2. In one of the embodiment oral dosage forms produced by inventive composition, having human administrable active ingredient is suitable for human use. Alternatively drug suitable for veterinary purpose formulated in accordance with present composition will be suitable for veterinary use.
According to the objective of present invention Metformin is formulated in oral dosage form for modified or extended release delivery. Inventi ve composition comprising 250, 500, 750, 800, 1 000 mg or 1 00 mg of Metform in in plurality of dosage formulations. Controlled release formulation can have combination of one or more additional drugs.
Suitable APIs that can be used with the present invention include, but are not limited to: andrenergic blocking agent; acetyl-cholin-esterase inhibitor; analgesic or antipyretics; angiotensin modulator; anthelmintic agents; ant! anxiety agent; antibacterial; antibiotic; anticoagulant; anticonvulsant; antidepressant; anti fungal ; ani i- histamine; antimalarial; antimicrobial agent; antipsychotic agent; Antiviral agents; blood glucose lowering drug; calcium channel modulator; diuretic; erectile dysfunction; gastric acid secretion inhibitor; histamine H2-receptor antagonist; inh ibitor of steroid Type II 5| alpha')- reductase including; lipid regulating agents; selective H l- receptor antagonist; vasodilator; vitamins. . . .
Following examples are offered to more fully illustrate the i nvention, but are not to be construed as limiting the scope thereof.
Mode for invention
Example 1 .
Preparation of Metformin Hydrochloride modified release tablets (500 mg) The dosage formulation for 100,000 (86.00 kg) Tablets of Metformin is prepared using composition as stated in table:- 1 wherein Metformin is 50.0 kg and 1 1 .20 kg of Instamodel (A43D00041 ) are weighed, sifted in rapid mixture granuiator accordingly, subsequently sieved to get uniformly granulated powder through 40 mesh screen. It is noted that other size screen could be used to get simi lar results. S ieved Metformin with above ingredients is granulated using water as granulating solvent . in rapid mixture granuiator (RMG) . It is recommended that RMG should be at slow speed for 1 5 m in fol lowed by high speed for 3-5 mins. Granulation step requires proper optimization of water quantity and continuous monitoring to avoid heavy granulation. If required extra water can be added gradually under continuous observation (to avoid heavy wet mass). Generated wet mass is sieved using ti20 screen (Multi-mill/ Fitzmi ll) dried in tray drier (or Fluidized. bed dryer) at temperature not more than 50CC-55°C keeping loss on drying at 1 -2%. Subsequently sift the dried granule using #30 mesh sieve on vibratory sifter and again sift on 1.0 mm screen at slow speed.
Further Mix the dried granule with 23.90 kg of Instamodel blend II (A43 D00042) for 10 min in a suitable blender (octagonal blender).
Table 1
Figure imgf000010_0001
[63]
Coating ingredients
Instacoat Universal (ICU- 2.580 kg(includes 20 % extra v > compensate pior ss
20 β
3849) white IH . losses
Purified water 20.S7 kg
Total 880J0
To promote efficient tablet punching further 0.50 kg of magnesium stearate and 0.40 kg of colloidal silicon dioxide sieved through 40 mesh screen is added to above dried blended formulation in blender for subsequent 5 minutes. Final screened granules are compressed using using 18.0 mm x 9.0 mm, capsule shaped, standard concave punches (for 860 mg average weight) circular, standard concave circular punches using arnavati Tablet Compression M/C- 1 7 Stn. GM.P machine at hardness not less than 15-25 kg/cm2. 7. The tablets are subjected to film coating using suitable film coating system. Film coating is done with normal immediate release film coating system i.e. Instacoat Universal (1CU - 3849 White) for weight gain of 2.0 - 2.5 % w/w'. Generated dosage form tablets are then subjected to film coating using Instacoat Universal.
Coating composition is weighed in accordance with table 1 and 1 1 % coating suspension is prepared in water with stirrer and mixed for about 45 minutes subsequently it is passed through 80 mesh screen. Coating is preformed on dosage form using IN S TACOAT Pharma nD coater (6' pan) at 25 rpm with inlet temperature being 53 °C and bed temperature at 40 °C. coating was done using I mm nozzle sprayer with peristaltic pump injecting coating suspension at the rate of I ml/min. Coated tablets are then dried and packed as per pharmacopoieal guidelines.
Example 2 Dissolution Profile Evaluation of Metformin tablet
Metformin dose form dissolution study was performed. Drug dissolution profiles of tablet prepared are measured by USP 35 dissolution test of rotating basket method <7 1 1>. It is evident from standard state of the art that active ingredient may have its own dissolution testing parameters which can be found in their respective monographs. The active ingredient content for present invention is standardized for sustained release profile is as per table 2:-
Medium: Phosphate buffer pH 6.8; 1000 ml
Time interval: 1 , 2, 3, 6 and 1.0 hour ( Test 1 & Test 2 of USP/NF 35, 2012.)
Table 2
Figure imgf000011_0001
The mean values are shown Sample size is of 1 0 tablets
It was observed that it shows maximum absorbance at 284 nm on Double Beam UV- VIS. Spectrophotometer (UV 2700- Thermo Fisher Scientific).
METFORMIN IN VITRO % DRUG RELEASE USING INSTAMODEL (A43D00041 AND A43D00042 DISSOLUTION COMPARISON
Figure imgf000011_0002
[75] Citapin X 500 mg B.No.0712042 (Aug)
Metformin HCI ER tab 500 mg using Instamodel Blend B.No RDIMBM038 ( Avg)
Figure imgf000012_0001
6 10
Time in lit s
The drug dissolved profile of the Reference products and Metformin having dos- strength of 500 mg using instamodel (A43D00041 and A43D00042) " ormulations are compared. The release exponents for the Reference and formulated Metformin is found to be having similar modified release profile indicating a predominantly diffusion based drug release mechanism.

Claims

Claims
A modified release solid pharmaceutical composition comprising Metformin, In stamodel (A43D00041 and A43D00042), solvent, binder, lubricant, glidant optionally opacifiers, colorants.
The solid pharmaceutical composition of claim l , wherein Metformin can be in form of salt, polymorphic form, its derivatives or mixture thereof.
The solid pharmaceutical composition of claim 1 , wherein binder is selected from polyvinyl polymers, Polyvinyl pyrrolidone 30 (PVP 30) and l ike. The solid pharmaceutical composition of claim i , wherei n sol vent is selected from water, isopropyl alcohol and like.
The solid pharmaceutical composition of claim 1 , wherein lubricant is selected from talc, magnesium stearate, stearic acid, sodium stearyl turn a rate and combination thereof.
The solid pharmaceutical composition of cla im 1 , wherein gl idant is selected from silicon di-oxide, colloidal sil icon dioxide and there derivatives thereof. A process for preparing Metformin tablet according to clai m 1 comprising a. Blending Instamodel (A43 D00041 ) with Metformi n.
... b.. Thorough mixing and Wet granulation with binder and solvent c. Sieving and drying
d. Again Blending with Instamodel (A43 D00042)
. e.. Addition of lubricant and glidant
.. . X, Final tablet compression
g. Optional film coating.
The solid pharmaceutical composition prepare using process for preparing Metformin tablet according to claim 1 comprising
... a. Blending Instamodel ( A43 D000 I ) with Metform i n
b. Thorough mixing and Wet granu lation with binder and sol vent c. Sieving and drying
d. Again Blending with Instamodel (A43 D00042)
e. Addition of lubricant and glidant
f. Final tablet compression
g. Optional film coating.
PCT/IN2014/000602 2014-09-16 2014-09-16 Extended release formulation of metformin WO2016042567A1 (en)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003039527A1 (en) * 2001-11-06 2003-05-15 Ranbaxy Laboratories Limited Controlled release tablets of metformin
US20030118647A1 (en) * 2001-12-04 2003-06-26 Pawan Seth Extended release tablet of metformin
US20040109891A1 (en) * 2002-08-02 2004-06-10 Penwest Pharmaceuticals Company Sustained release formulations of metformin
WO2004110422A1 (en) * 2003-06-16 2004-12-23 Ranbaxy Laboratories Limited Extended-release tablets of metformin
WO2006082523A2 (en) * 2005-01-25 2006-08-10 Aurobindo Pharma Limited Pharmaceutical sustained release composition of metformin

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003039527A1 (en) * 2001-11-06 2003-05-15 Ranbaxy Laboratories Limited Controlled release tablets of metformin
US20030118647A1 (en) * 2001-12-04 2003-06-26 Pawan Seth Extended release tablet of metformin
US20040109891A1 (en) * 2002-08-02 2004-06-10 Penwest Pharmaceuticals Company Sustained release formulations of metformin
WO2004110422A1 (en) * 2003-06-16 2004-12-23 Ranbaxy Laboratories Limited Extended-release tablets of metformin
WO2006082523A2 (en) * 2005-01-25 2006-08-10 Aurobindo Pharma Limited Pharmaceutical sustained release composition of metformin

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
IDEAL CURE PVT.LTD: "Extended Release Tablets Formulation Simplified", 19 July 2012 (2012-07-19), Retrieved from the Internet <URL:http://news.cision.com/ideal-cures-pvt--ltd/r/extended-release-tablets-formulation-simplified,c9285826> *

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