WO2017060920A1 - Compositions pharmaceutiques - Google Patents

Compositions pharmaceutiques Download PDF

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Publication number
WO2017060920A1
WO2017060920A1 PCT/IN2016/050337 IN2016050337W WO2017060920A1 WO 2017060920 A1 WO2017060920 A1 WO 2017060920A1 IN 2016050337 W IN2016050337 W IN 2016050337W WO 2017060920 A1 WO2017060920 A1 WO 2017060920A1
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WO
WIPO (PCT)
Prior art keywords
pharmaceutically acceptable
ibuprofen
cellulose
glidant
sodium
Prior art date
Application number
PCT/IN2016/050337
Other languages
English (en)
Inventor
Gurubalaji SUNDARARAJAN
Shubhrangshu Shekher SARKER
Selvakumar Ramalingam
Sampathkumar Devarajan
Original Assignee
Strides Shasun Limited
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.)
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Publication date
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Publication of WO2017060920A1 publication Critical patent/WO2017060920A1/fr

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Classifications

    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • 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
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1682—Processes
    • A61K9/1694—Processes resulting in granules or microspheres of the matrix type containing more than 5% of excipient

Definitions

  • the present invention relates to pharmaceutical compositions of Ibuprofen or its pharmaceutically acceptable salt, enantiomers thereof and methods of preparing them. Particularly, the present invention relates to a cost effective method of producing stable pharmaceutical compositions of Ibuprofen or its pharmaceutically acceptable salts, enantiomers thereof.
  • the process of the present invention particularly involves the use of glidant in three stages of formulation to obtain free flowing granules that impart better release properties and minimize the tablet weight variation.
  • Ibuprofen chemically known as 2-(4 ⁇ isobutyl phenyl) propionic acid, is a well- known medicament or NSAID with anti- inflammatory, antipyretic, and analgesic activities.
  • Ibuprofen is primarily used for the treatment of pain and inflammation in musculoskeletal disorders such as rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, postoperative pain, post partum pain, headache, backache, neuralgia, dysmenorrhoea, dental pain, colds and flu and soft tissue injuries, generally at doses up to 3200 mg per day.
  • Ibuprofen and its compositions are disclosed in US3228831 and US3385886.
  • Active ingredients with a low melting range such as ibuprofen or its pharmaceutically acceptable salts, especially the sodium salt, that is described as fluffy, soft, sticky, especially poorly compressible and also as having a poor ability to be granulated, can lead to serious difficulties in the processing of formulation, as a consequence of sintering processes and through sticking to the punch and die plates of the tablet press and low tableting speeds.
  • compositions produced by wet granulation method require relatively large percentages of excipients to produce a compressible formulation, leading to increase in tablet size which is undesirable both from manufacturing and handling standpoint and a patient acceptability standpoint.
  • US4609675 discloses a method of preparing a pharmaceutical ibuprof en- containing granulate composition suitable for preparing tablets of relatively high dosage. This is accomplished by dry mixing ibuprofen with 1 to 15 percent by weight of croscarmellose sodium as disintegrant and small amounts of colloidal silica with short mixing times in the region of a few minutes, and is subsequently roll -compacted. Croscarmellose sodium is a relatively expensive additive and it contributes significantly to the cost of the formulation. An insufficient improvement in tablet ability is achieved with these formulations.
  • US4806358 discloses tablet composition manufactured through aqueous/non- aqueous granulation comprising ibuprofen or a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable effervescent couple that produces carbon dioxide in the presence of water, a pharmaceutically acceptable surfactant, a pharmaceutically acceptable water-insoluble hydrophilic polymer consisting of microcrystalline cellulose and croscarmellose sodium and a saccharide, for example sucrose, lactose, dextrose or sorbitol, to enhance the stability of the composition dispersed therein.
  • the physico chemical stability of effervescent formulations is relatively less comparable to conventional formulations and need special precautions and packaging materials.
  • US4839176 discloses a stable composition comprising ibuprofen or a pharmaceutically acceptable salt thereof, codeine or a pharmaceutically acceptable salt thereof together with a sufficient amount of pharmaceutically acceptable insoluble salt of carboxymethyl cellulose to prevent discoloration of the composition.
  • the composition based on ibuprofen and codeine is ineffective and is not patient compliant.
  • US4859704 discloses water soluble alkali metal salt (potassium and sodium) of ibuprofen prepared by reacting ibuprofen and alkali metal bicarbonate in an aqueous medium. This process of wet granulation involves the evolution of C0 2 gas, which may lead to pressurization inside the reactor which makes the process less attractive.
  • US4904477 discloses a spray dried ibuprofen composition suitable for direct compression into tablets and include a spray dried dispersion in water of ibuprofen, pregelatinized starch, a disintegrate and a wetting agent. Spray drying is a complex granulation method, which involves use of high temperatures.
  • US4911921 provides a granular pharmaceutical composition containing t ibuprofen, binder, and polyvinyl pyrrol i done, wherein the polyvinyl pyrrol i done forms a film with a portion of said binder to form agglomerates.
  • the process for preparing the tablets includes fluidizing Ibuprofen with a portion of the binder in a fluid bed apparatus and spraying the aqueous dispersion of polyvinylpyrrolidone and the remainder of the binder.
  • the granulation may be subsequently blended with additional excipients and, optionally, additional active pharmaceutical ingredients for direct compression into tablets.
  • the process requires extra processing steps involving sophisticated equipment and a relatively high operating cost.
  • US5191114 discloses a process for producing ibuprofen powders for direct tableti ng, in which powders with improved flowability are said to be obtained by dry mixing of ibuprofen with amorphous silica gel.
  • Direct compressible ibuprofen particles are also formed by treating commercially available, dry ibuprofen with a hydrophilic solvent or a mixture of a hydrophilic solvent and one or more hydrophobic organic solvents so as to change at least the external crystalline shape of the ibuprofen from a flow- retarding shape to a free-flowing, easily compressible configuration.
  • a typical hydrophilic solvent is water and among the hydrophobic solvents which may be used are acetone, methyl alcohol, ethyl alcohol, isopropyl and N-propyl alcohol.
  • the flowability can be improved in this way after only a short mixing time.
  • the tablet ability is not improved in practice in this way.
  • US5445827 relates to an effervescent ibuprofen preparation
  • an effervescent ibuprofen preparation comprising a) basic granules consisting of 1 part by weight of water-soluble ibuprofen salt preferably sodium salt, 2 to 10 parts by weight of excipient, 0.3 to 0.8 part by weight of stabilizer and 0.1 to 1 part by weight of sodium carbonate or potassium carbonate and b) 1 to 4 parts by weight of an acid component.
  • the patent did not have the object to describe (the preparation of) a very water soluble ibuprofen granulates in an efficient and cheap manner from insoluble ibuprofen.
  • the physico chemical stability of effervescent formulations is relatively less comparable to conventional formulations and thus need special precautions and packaging materials.
  • US 5320855 discloses a chewable medicament tablets made from coated rotogranules of a medicament wherein the rotogranules are formed from a wet granulation mixture of medicament, e.g. ibuprofen, polyvinylpyrrolidone, sodium starch glycolate and sodium lauryl sulfate and the rotogranules are coated with hydroxyl ethyl cellulose or a mixture of hydroxyl ethyl cellulose and hydroxyl propyl methyl cellulose and a process for making such tablets and a method of providing taste masking of medicaments utilizing such coated rotogranules in a tablet. While resulting in a significant taste improvement, this method has been found not to completely eliminate the ' throat burn_ associated with ibuprofen in chewabl e dosage forms.
  • medicament e.g. ibuprofen, polyvinylpyrrolidone, sodium starch glycolate and sodium lauryl sulfate and the
  • US5696165 discloses the use of the sodium salt of S(+)-ibuprofen di hydrate with a pharmaceutical composition comprising 10-99% wA/v of S(+)-ibuprofen sodium; 1-90% w/w of a diluent; 0.1-10% w/w of a lubricating agent; 0.1-15% w/w of a disintegrating agent; optionally 0.1-15% w/w of a binder and optionally 0.1-10% of a flow aid. It permits the preparation of a tablet using wet granulation technique comprising dissolving polyvinyl pyrrolidone in a mixture of isopropanol and water (1 :1 parts by vol ume) .
  • US6197336 discloses a tablet composition comprising ibuprofen, arginine, linear poly vinyl pyrrolidone, and alkaline bicarbonate having good workability and fast dissolution so as to assure a prompt analgesic effect.
  • the patent states that it is possible that during preparation of the composition and/or tablets, some interaction or reaction may occur between two or more components, but it is silent about the extent and type of such interaction.
  • the tablets containing 200 mg ibuprofen weigh 600 mg which is rather large for such dosage; tablets containing 400 mg ibuprofen weigh 980 mg which can hardly be swallowed.
  • the large quantity of expensive arginine required significantly increases the costs.
  • US 8846085 discloses a directly tabletable ibuprofen formulation comprising crystalline ibuprofen; finely divided silica with a surface area of at least 100 rr /g together with pharmaceutically acceptable excipients wherein at least 50% of the surface of the ibuprofen crystals is covered with finely divided excipient.
  • US20020034540 discloses a solid non-effervescent compressed dosage form comprising ibuprofen combined with a disintegrating component.
  • the composition comprises a carrier material such as alkali metal carbonate or bicarbonate in an amount such that the dosage form has a crushing strength in the range 6.5-15K p and a disintegration time of less than 10 minutes.
  • the dosage form is supposedly particularly advantageous to the formulation with the poorly compressible alkali metal salts and especially the sodium salt, that is described as fluffy, soft sticky, especially poorly compressible and also as having a poor ability to be granulated.
  • US20020034540 discloses the wet granulation process comprising pre-granulating ibuprofen with a binder, such as polyvinyl pyrrol i done in water or hydrocarbon solvent.
  • US20040102522 provides directly compressible dosage form of sodium ibuprofen and discloses a non -effervescent tablet of ibuprofen, comprising a tablet core and, if desired, a sugar or film coat, wherein the tablet core, based on the weight of the tablet core, consists of 50 to 100% by weight sodium ibuprofen hydrate and 50 to 0% by weight auxiliary material component and contains no lubricant and no disintegrant, and wherein the sodium ibuprofen hydrate has a water content of 8 to 16% by weight preferably 11 to 16% by weight, possesses a sufficient hardness, is comparably small and leads to a particularly rapid increase in blood level and thereby to an accelerated onset of analgesic effect.
  • the tablets only possess sufficient not optimal hardness and contain large total sodium content which is not advantageous to patients, especially frequent and daily users of such over the counter medicaments. Further, crumbling and breakage of such tablets prior to ingestion may lead to uncertainty as to the dosage of active ingredient per tablet and core defects, including picking and sticking. Furthermore, high friability also causes tablet breakage leading to waste during factory handling.
  • US20100323005 discloses sodium ibuprofen compositions and methods of manufacturing tablets and caplets using roller compaction. Tablets made by roll compaction often show inferior tensile strength compared to tablets prepared by wet granulation or direct compaction. Because this phenomenon is more profound in plastic substances, adjusting the plastic/brittle balances of starting materials by selecting appropriate excipients is much more. A lso, minimum compaction force should be used, as well as a smaller particle size of starting powder is required. A second disadvantage of roll compaction is the production of noniiompacted powder. Because no liquid binder is used, high amounts of fines remain and less product yield is obtained.
  • compositions of ibuprofen and processes for preparation include; (a) inadequate bulk density of ibuprofen or its pharmaceutically acceptable salt granules to obtain a reasonably sized tablet; (b) punch filming, picking or sticking during compression; (c) obtaining poor flowing granulation formulation which are difficult to handle in typical pharmaceutical plant scale equipment; (e) excessive disintegration time, Lamination and friability problems; (f) using alcohol especially ethanol during wet granulation requires special equipment which is highly undesirable.
  • the present invention addresses these and other problems associated with the prior art by providing technically feasible process for manufacturing ibuprofen or it ' s pharmaceutically acceptable salts, enantiomers thereof, being blended with external excipients to produce a formulation capable of being directly formed into a tablet or caplet having suitable hardness, short disintegration time and fast dissolution time.
  • the method provides suitable blending of ibuprofen or ifs pharmaceutically acceptable salts, enantiomers thereof with suitable pharmaceutically acceptable excipients for tabletization so as to achieve a long production cycle running for as many hours as possible without compromising on standards.
  • the present invention provides a method/process for preparing a stable pharmaceutical composition of Ibuprofen or its pharmaceutically acceptable salts, enantiomers thereof which are adaptable to final formulations having a variety of dosage forms such as compressed tablets, caplets and filled capsules with varying dosage size.
  • the present invention provides a method of preparing stable pharmaceutical composition of Ibuprofen or its pharmaceutically acceptable salts, enantiomers thereof, characterized in that the glidant used is added in pre- bl ending, blending and lubricating stage of said process; comprising;
  • step (ii) Milling the granules of step (i) and mixing with glidant to form a pre- blend mixture;
  • step (iii) Blending mixture of step (ii) with one or more pharmaceutically acceptable excipients and a glidant;
  • step (iv) Lubricating the blend of step (iii) with one or more pharmaceutically acceptable excipients and glidant,
  • step (v) Formulating the blend obtained in step (iv) into a suitable dosage form
  • the method of producing said pharmaceutical composition comprises dry granulation or wet granulation, preferably wet granulation.
  • the pharmaceutically acceptable excipients for the process are selected from diluents, binders, disintegrants, glidants, lubricants, surfactants, flavorants, colors, and such like alone or in combination thereof.
  • the granules obtained by the process of the present invention are further compressed in to tablets or caplets or as filled capsules in a suitable dosage size.
  • the pharmaceutical composition of ibuprofen or its pharmaceutically acceptable salts, enantiomers thereof may contain other suitable active ingredients.
  • the present invention provides stable pharmaceutical composition with short disintegration time and increased dissolution rate without being unacceptably friable comprising;
  • one or more pharmaceutically acceptable fillers/diluents in an amount of about 20 percent or more on a dry weight basis; iii. one or more pharmaceutically acceptable wetting agents/surfactants in an amount of about 0.1 percent or more on a dry weight basis; iv. one or more pharmaceutically acceptable disintegrants in an amount of about 3 percent or more on a dry weight basis; v. one or more pharmaceutically acceptable binders in a binding amount of about 2 percent or more on a dry weight basis; vi. one or more pharmaceutically acceptable lubricants in an amount of about 1 percent or more on a dry weight basis; and
  • one or more pharmaceutically acceptable glidants in an amount of about 1 percent or more on a dry weight basis.
  • the present invention relates to novel pharmaceutical granulation, comprising ibuprofen or its pharmaceutically acceptable salts, enantiomers thereof, having specific advantageous properties including (a) excellent physical stability, especially regarding compressed tablets dissolution properties, (b) high bulk density, (c) excellent bioavailability and (d) excellent processing properties in pharmaceutical plant equipment including good flowability, no sticking or picking during compression process or filling into capsules.
  • ' tablets is intended to comprise tablets, caplets, capsule shaped tablets, pills or any other synonym thereof.
  • ' tablet refers to a pharmacological composition in the form of a small, essentially solid pellet of any shape. Tablet shapes maybe cylindrical, spherical, rectangular, capsular, or irregular.
  • the term ' about , (or ' approximately , ) means a particular value can have a range acceptabl e to those of ski 11 i n the art given the nature of the val ue and method by which it is determined.
  • the present invention discloses a method of preparing stable granular pharmaceutical composition of Ibuprofen or its pharmaceutically acceptable salts, enantiomers thereof, characterized in that the glidant used is added in pre- blending, blending and lubricating stage of said process; comprising;
  • step (iii) Blending mixture of step (ii) with one or more pharmaceutically acceptable excipients and a glidant;
  • step (iii) L ubricating the blend of step (iii) with one or more pharmaceutically acceptable excipients and glidant,
  • step (iv) Formulating the blend obtained in step (iv) into a suitable dosage form
  • the method or process of producing said pharmaceutical composition comprises dry granulation or wet granulation, preferably wet granulation.
  • the solvents for wet granulation are selected from water, isopropyl alcohol, ethanol and/or mixtures thereof.
  • the pharmaceutically acceptable excipients for the process are selected from diluents/fillers, binders, disintegrants, glidants, lubricants, surfactants, flavoring agnets, colors, lubricants, souring agents, sweeteners, and wetting agents/surfactants and such like alone or in combination thereof.
  • the glidants are used in the present invention to improve the flow of the powder blend, to impart better mold release properties and minimize tablet weight variation.
  • the Glidant is selected from the group comprising of talc, silicon dioxide, silicic acid, cornstarch, maize starch or starch derivatives, calcium silicate, magnesium carbonate, magnesium oxide, magnesium silicate, colloidal silicon dioxide, starch, castor wax and combination thereof.
  • talc silicon dioxide
  • silicic acid cornstarch
  • maize starch or starch derivatives calcium silicate, magnesium carbonate, magnesium oxide, magnesium silicate, colloidal silicon dioxide, starch, castor wax and combination thereof.
  • glidants could be added or substituted to formulate the compositions contemplated herein.
  • the glidants are used in an amount ranging from 0.1 to 30%.
  • the binder used in the present granulation refers to one or more ingredients added before or during granulation to form granules and/or promote cohesive compacts during compression.
  • the binder component of the present granulation serves to impart good binding and disintegrant properties to the final dosage forms prepared from the granulation, i.e., tablets. It is included in an amount effective for imparting to the granulation and formulations made there from, the capability of being formed into tablets having optimum hardness, disintegration time, and short dissolution time when compared against marketed one.
  • Binders of the present invention is selected from starches and starch derivatives, celluloses, sugars, polymers like pregelatinized starch, corn starch, microcrystalline cellulose, lactose, sucrose, mannitol, silicon dioxide, vinyl pyrrolidone vinyl acetate copolymers, polyvinyl alcohol based compositions, hydroxyl propyl methyl cellulose, hydroxyl propyl cellulose, methyl cellulose, ethyl cellulose, hydroxyl ethyl cellulose, carboxymethyl cellulose and natural gums (e.g., gum acacia, gum tragacanth, etc.) and synthetic polymer binders like polyvinylpyrrolidone, hydrocolloids, sugars, povidone, copovidone, methacrylic acid copolymers and combination or compatible mixtures of two or more such materials in the range of 0.1 to 20%w/w.
  • Diluent/filler used in the present invention generally are auxiliary materials that i mprove the compressi bi I i ty.
  • P ref erabl y the di I uents/f i 11 ers are sel ected that neutral to weakly acidic and can improve the compressibility which include cellulose and its derivatives like microcrystalline cellulose, silicified microcrystalline cellulose, powdered cellulose, carbohydrates and polyalcohol such as lactose, sucrose, dextrose, saccharose, glucose, fructose, xylitol, mannitol, sorbitol, lactitol, maltitol, starch, modified starches, hydrolysed or enzymatically split starch such as maltodextrin, cyclodextrins such as ⁇ - and .-.cyclodextrin, non- cross linked (water soluble) polyvinylpyrrolidone, polyvinyl alcohols, polyethylene glycols, polyprop
  • Disintegrant which provide superior bioavailability of the medicament in the granulations include but is not limited to cross linked vinylic polymers such as cross-linked polyvinylpyrrolidone (crospovidone), polyvinyl pyrrolidine or sodium starch glycolate.
  • cross linked vinylic polymers such as cross-linked polyvinylpyrrolidone (crospovidone), polyvinyl pyrrolidine or sodium starch glycolate.
  • Other useful disintegrants may comprise derivatives of starch and of cellulose such as sodium carboxy methyl-starch and cross linked sodium carboxy methyl cellulose (croscarmellose sodium), cross linked calcium carboxy methyl cellulose, microcrystalline cellulose, carboxy methyl cellulose, hydroxyl propyl cellulose, low-substituted hydroxyl propyl cellulose, alginic acid, sodium alginate, potassium alginate, calcium alginate, an ion exchange resins, calcium silicate, a metal carbonate, sodium bicarbonate, calcium citrate, or calcium phosphate starch and modified starches including pregelatinized starch, formal in- casein, alginates, gums and combination or and mixtures thereof.
  • the disintegrant is present in the range from 0.1 to 30%.
  • SLS Sodium lauryl sulfate
  • H L B hydrophi I i c-l i pophi I i c balance
  • surfactants may include cationic, anionic and nonionic surfactants, sodium lauryl sulfate, monooleate, monolaurate, monopalmitate, monostearate or another ester of polyoxyethylene sorbitane, sodium dioctylsulfosuccinate, lecithin, stearylic alcohol, cetostearylic alcohol, cholesterol, polyoxyethylene ricin oil, polyoxyethylene fatty acid glycerides, poloxamer, potassium and sodium oleates and polysorbates.
  • T he surfactants are used in the range of 0.1 to 10%
  • flavors e.g., burnt sugar flavor, strawberry aroma, raspberry aroma, cherry flavor, magnasweet 135, key lime flavor, grape flavor, fruit extracts and prosweet
  • flavor enhancers and sweeteners e.g., sucralose, aspartame, sodium saccharine, sorbitol, glucose, sucrose
  • souring agents e.g. citric acid
  • dyes or colorants e.g., dyes or colorants.
  • the present invention relates to a method/process of preparing a stable pharmaceutical composition of Ibuprofen or its pharmaceutically acceptable salts, enantiomers thereof, wherein the glidant used is added in pre- blending, blending and lubricating stage of said process; comprising;
  • step (i) Milling the granules of step (i) and mixing with glidant in an amount of about 1.5%w/w to form a pre-blend mixture;
  • the granulation thus produced could be directly compressed to form tablets.
  • better tablets are produced by blending the granulation by known methods, such as using double cone blender, with additional excipients that aid in the compression and provide improved properties such as hardness and excellent disintegration time.
  • excipients may be selected from the whole range known in the art and are chosen in the present invention based on the desired properties of the tablet produced.
  • a lubricant that aids in the production of the tablets to facilitate ejection of the finished tablet from dies after compression and to prevent tablets from sticking to punch faces and each other.
  • lubricants are stearic acid, metal stearates like calcium/magnesium/sodium stearate, sodium stearyl fumarate, leucine, glycerol behenate, sodium benzoate, talc, silicon dioxide, silicic acid, colloidal silicon dioxide, mineral oil, fumaric acid, sodium stearyl fumarate, stearic acid, talc, vegetable oil, castor wax and combination thereof and polyethylene glycol, poloxamers, sodium lauryl sulfate, micro crystalline cellulose and hydrogenated vegetable oils.
  • lubricants could be added or substituted to formulate the compositions contemplated herein.
  • the lubricants are used in an amount ranging from 0.1 to 10%.
  • the pharmaceutical granules of ibuprofen or its pharmaceutically acceptable salts or enantiomer thereof obtained by the process of the present invention is further compressed in to tablets or caplets or as filled capsules and can be formulated in dosage size ranging from 100 to 1200mg per dosage unit.
  • the present invention discloses stable pharmaceutical composition with short disintegration time and increased dissolution rate without being unacceptably friable comprising;
  • one or more pharmaceutically acceptable binders in a binding amount of about 2 percent or more on a dry weight basis
  • one or more pharmaceutically acceptable glidants in an amount of about 1 percent or more on a dry weight basis.
  • the pharmaceutical composition comprises a coated core having at least one coating, comprising a sugar or film coating with pharmaceutically acceptable coating agents, in which all customary sugar and film coating materials are in principle suitable as coating materials.
  • the thickness of the coat is not critical; however in general the proportion of the coat, based on the weight of the tablet core, is only about 1 to 25% by weight, preferably about 2 to 6% by weight.
  • the stable pharmaceutical composition with short disintegration time and increased dissolution rate without being unacceptably friable comprises;
  • a pharmaceutically acceptable filler preferably lactose on a dry weight basis
  • a pharmaceutically acceptable surfactant preferably sodium lauryl sulphate on a dry weight basis
  • a pharmaceutically acceptable disintegrant preferably crospovidone or its derivatives on a dry weight basis
  • a pharmaceutically acceptable binder preferably poly vinyl pyrrolidone or its derivatives on a dry weight basis
  • a pharmaceutically acceptable lubricant preferably a metal stearate on a dry weight basis
  • one or more pharmaceutically acceptable glidants in an amount of about 1 percent or more on a dry weight basis.
  • the method of preparing the granulation described by a wet granulation method comprises, Sifting the composition components of the present invention selected from diluent, surfactant, disintegrant including Ibuprofen or its pharmaceutically acceptable salts and dry mixing for not less than 5 minutes. Granulating the dry mix in RMG using binder solution prepared using water or alcoholic or hydro-alcohol. Drying the resulting granules using FBD followed by milling/sizing and mixing the granules with a part of glidant for not less than 10- 20minutes. Further blending with diluent, disintegrant and a part of the glidant of not I ess than 3- 10 mi nutes.
  • the manufacturing process of the present invention involves the use of glidant in three stages of formulation i.e. pre- blending, blending and lubrication and at 1.5, 1.0 and 0.5%w/W approximately respectively.
  • the amounts of the added excipients are preferably the minimum amounts necessary to accomplish their purposes.
  • the lubricant component is present in a lubricating amount sufficient to impart mold release properties to tablets formed from the formulation and preferably insufficient to increase disintegration time and dissolution time of such tablets, and preferably insufficient to decrease the hardness obtainable for tablets formed from a formulation having no additional lubricant.
  • the final drug forms (resulting from the new granulation formulations) will have specific advantageous properties including (a) excellent physical stability, especially regarding compressed tablet s dissolution properties, (b) high bulk density (c) excellent bioavailability and (d) excellent processing properties in pharmaceutical plant equipment including good flowability, minimal tablet punch or plunger sticking during compressing or capsule filling and good compression characteristics.
  • composition of the present invention obtained by the process exhibits a significant improvement in dissolution profile and assay during stability in stress and accelerated condition as compared to marketed formulation.
  • E xample 5 Wet granulation method of producing the Ibuprofen granules Sifted Ibuprofen sodium di hydrate, Lactose monohydrate, Sodium lauryl sulphate, Crospovidone through mesh. Prepared the binder solution with povidone and Isopropyl alcohol. Loaded the sifted Ibuprofen sodium dihydrate, lactose monohydrate, Sodium lauryl sulphate, crospovidone into Rapid Mixer Granulator (RMG) and mixed for 10 minutes. Granulated the dry mix using povidone binder solution. Dried the granules in Fluid Bed Drier (FB D) followed by Sizing & milling.
  • FB D Fluid Bed Drier

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Abstract

L'invention concerne une composition pharmaceutique d'ibuprofène ou son sel acceptable sur le plan pharmaceutique, des énantiomères de celui-ci et des procédés de préparation associés. La présente invention concerne en outre un procédé rentable de production de compositions pharmaceutiques stables d'ibuprofène ou de ses sels pharmaceutiquement acceptables, des énantiomères de celui-ci. Le procédé de la présente invention implique l'utilisation d'un agent de glissement dans trois étages de formulation pour obtenir des granulés à écoulement libre qui confèrent de meilleures propriétés de démoulage et réduisent au minimum la variation de poids des comprimés.
PCT/IN2016/050337 2015-10-05 2016-10-05 Compositions pharmaceutiques WO2017060920A1 (fr)

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IN5304CH2015 2015-10-05
IN5304/CHE/2015 2015-10-05

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Cited By (3)

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Publication number Priority date Publication date Assignee Title
CN107970221A (zh) * 2017-12-13 2018-05-01 南京迈迪信泽医药科技开发有限公司 一种布洛芬片及其制备方法
CN112137966A (zh) * 2020-10-28 2020-12-29 哈药集团技术中心 一种布洛芬颗粒剂及其制备方法
WO2022114240A1 (fr) * 2020-11-30 2022-06-02 Ssp Co., Ltd. Préparation solide contenant de l'ibuprofène

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2063141A1 (fr) * 1989-08-04 1992-10-18 Edward J. Roche Rotogranulations et enrobages sapides pour des preparations de comprimes pharmaceutiques croquables
US5445827A (en) * 1988-11-12 1995-08-29 Bayer Aktiengesellschaft Effervescent ibuprofen preparations
US20020034540A1 (en) * 1996-02-21 2002-03-21 Ian Ashley Price Dosage form of ibuprofen

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5445827A (en) * 1988-11-12 1995-08-29 Bayer Aktiengesellschaft Effervescent ibuprofen preparations
CA2063141A1 (fr) * 1989-08-04 1992-10-18 Edward J. Roche Rotogranulations et enrobages sapides pour des preparations de comprimes pharmaceutiques croquables
US20020034540A1 (en) * 1996-02-21 2002-03-21 Ian Ashley Price Dosage form of ibuprofen

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107970221A (zh) * 2017-12-13 2018-05-01 南京迈迪信泽医药科技开发有限公司 一种布洛芬片及其制备方法
CN112137966A (zh) * 2020-10-28 2020-12-29 哈药集团技术中心 一种布洛芬颗粒剂及其制备方法
WO2022114240A1 (fr) * 2020-11-30 2022-06-02 Ssp Co., Ltd. Préparation solide contenant de l'ibuprofène

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