WO2002087547A1 - An improved process for preparation of four-drug anti-tubercular fixed dose combination - Google Patents
An improved process for preparation of four-drug anti-tubercular fixed dose combination Download PDFInfo
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- WO2002087547A1 WO2002087547A1 PCT/IN2001/000093 IN0100093W WO02087547A1 WO 2002087547 A1 WO2002087547 A1 WO 2002087547A1 IN 0100093 W IN0100093 W IN 0100093W WO 02087547 A1 WO02087547 A1 WO 02087547A1
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- WIPO (PCT)
- Prior art keywords
- granules
- rifampicin
- binder material
- mixture
- isoniazid
- Prior art date
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4409—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 4, e.g. isoniazid, iproniazid
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
-
- 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
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
Definitions
- the invention relates to an improved process for preparation of a composition comprising fixed dose combination (FDC) of four anti-tubercular drugs viz rifampicin, isoniazid, pyrazinamide and ethambutol hydrochloride, which improves the dissolution of poorly soluble drug rifampicin and hence improve its bioavailability
- FDC fixed dose combination
- the ⁇ n ⁇ ent ⁇ on further relates to an improved process for preparation of a composition comprising fixed dose combination (FDC) of four anti-tubercular drugs viz rifampicin, isoniazid, pyrazinamide and ethambutol hydrochloride, which improves the dissolution of poorly soluble drug rifampicin and hence improve its bioavailability, without use of a surfactant
- tuberculosis remains a major health problem in India
- WHO World Health Organization
- DOT Directly Observed Therapy
- SCC Short Course Chemotherapy
- the initial phase consists of four drugs viz. rifampicin, isoniazid, pyrazinamide and ethambutol hydrochloride given daily for two months and the second or continuation phase consists of two drugs viz. isoniazid and rifampicin given daily or intermittently.
- Monotherapy is prevented, consecutively the risk for drug resistant bacilli is reduced.
- the two, three and four-drug FDCs recommended by WHO and included in the WHO model list of essential drugs contain varying compositions of each drug based on the age, gender and weight of the patients they are intended for. To ensure that the process used for manufacturing the entire range of FDCs with variable active ingredient compositions is economically viable, a flexible process by means of which all the different compositions can be manufactured must be available.
- Japanese Patent No. 53-133624 discloses a formula for overcoming poor elution properties of solid pharmaceutical preparations containing rifampicin.
- Capsules containing mixtures of rifampicin with crystalline cellulose alone or with crystalline cellulose together with polyethyleneglycol 40 monostearate, polyethyleneglycol 80 sorbitan monooleate, glycerol monostearate, hydroxypropyl cellulose or hydroxypropyl methylcellulose and magnesium stearate showed satisfactory elution properties when tested in a medium with a pH of 1.5 or 3, using the rotating basket method.
- United States Patent No. 4,613,496 discloses capsules containing a mixture of rifampicin, crystalline cellulose, sodium lauryl sulfate and magnesium stearate, which show consistently more uniform and more complete dissolution rates using the column method than those of the compositions disclosed in the above Japanese patent.
- United States Patent No. 5,104,875 discloses combination preparations containing rifampicin and thioacetazon and optionally isonicotinic acid hydrazide or ethambutol and its use for the treatment of mycobacterial infections.
- United States Patent No. 6,107,276 discloses a technique for improving the dissolution of slightly soluble drugs by employing a water-swellable, but water-insoluble cross-linked polymer, a surface-active agent and an oil mixed with the drug for improving its bioavailability.
- European Patent EP 330284 Bl discloses a wet granulation process for making good quality granulate comprising of a drug present in high concentration but having limited solubility in water of less than 10 wt %, 20 -100 wt % of microcrystalline cellulose or microfine cellulose or a mixture of both and 0-0.5 wt % of a wet granulation binding substance. These granulates can be processed to solid tablets having a satisfactory disintegration behaviour.
- the Indian Patent No. 181730 discloses a wet granulation process for manufacture of tablets containing rifampicin, isoniazid, pyrazinamide and ethambutol hydrochloride along with pharmaceutically acceptable excipients, stabilizers and non-ionic surfactants.
- This four-drug FDC is claimed to exhibit stability and bioavailability, which is comparable with single drug dosage forms containing equivalent amount of the drugs. Two processes are described for manufacture of four-drug FDCs.
- rifampicin and ethambutol hydrochloride are to be wet granulated with excipients and isoniazid and pyrazinamide wet granulated with excipients followed by mixing and compression of granules obtained in these two steps.
- the other process teaches wet granulating rifampicin separately with excipients and the other 3 drugs together with excipients, mixing and compression of granules obtained in these two steps.
- These processes are hereinafter referred to as 2-step granulation processes.
- the disadvantages of the processes described lie in the fact that since 2 or more ingredients are granulated together, it is not possible to use the same granules to manufacture other FDCs having different strengths of the drugs.
- a composition when formulated in a proper way can have acceptable disintegration time and show better dissolution profile for a drug like rifampicin leading to increased bioavailability.
- the direct compression method is not suitable for the four drug FDC as the actives have a very poor flow thus leading to processing problems during compression.
- the dry granulation method is also not advisable due to hygroscopic nature of ethambutol hydrochloride, which leads to heavy sticking on the rollers of compactor during compaction.
- the wet granulation method is the most preferred method as it leads to uniform particle size distribution, homogeneous mixture with free flowing properties and better compressibility.
- rifampicin, isoniazid, pyrazinamide and ethambutol are granulated by a wet granulation process that is a 3-step or a 4-step process, surprisingly, the bioavailability of rifampicin is improved as compared to the 2-step granulation process patented earlier.
- rifampicin is granulated separately, isoniazid and pyrazinamide together and ethambutol hydrochloride is granulated separately.
- all the four-drugs viz. rifampicin, isoniazid, pyrazinamide and ethambutol hydrochloride are granulated separately.
- Surfactants are used as wetting agents to improve dissolution of poorly soluble drugs.
- the surfactants which can be used for this include anionic surfactants such as sodium lauryl sulfate (SLS), docusate sodium (dioctyl sodium sulfosuccinate) or non-ionic surfactants such as glyceryl monooleate, polyoxyethylene sorbitan fatty acid esters such as polysorbate 80.
- anionic surfactants such as sodium lauryl sulfate (SLS), docusate sodium (dioctyl sodium sulfosuccinate) or non-ionic surfactants such as glyceryl monooleate, polyoxyethylene sorbitan fatty acid esters such as polysorbate 80.
- the object of the present invention is to provide an improved process for the preparation of stable and bioavailable anti-tubercular pharmaceutical composition of fixed dose combination of all four first line anti-tubercular drugs viz. rifampicin, isoniazid, pyrazinamide and ethambutol hydrochloride using a wet granulation manufacturing process.
- the further object of the invention is to provide an improved process for the preparation of stable and bioavailable anti-tubercular pharmaceutical composition of fixed dose combination of all four first line anti-tubercular drugs viz. rifampicin, isoniazid, pyrazinamide and ethambutol hydrochloride using a wet granulation manufacturing process wherein rifampicin bioavailability is not adversely affected.
- One more object of the invention is to provide an improved process for the preparation of stable and bioavailable anti-tubercular pharmaceutical composition of fixed dose combination of all four first line anti-tubercular drugs viz. rifampicin, isoniazid, pyrazinamide and ethambutol hydrochloride using a wet granulation manufacturing process, which does not involve use of a surfactant.
- Another object of the present invention is to provide an improved process for the preparation of stable and bioavailable anti-tubercular pharmaceutical composition of fixed dose combination of all four first line anti-tubercular drugs viz rifampicin, isoniazid, pyrazinamide and ethambutol hydrochloride using a wet granulation manufacturing process wherein rifampicin is protected against interaction with other drugs present in the composition
- Yet another object of the present invention is to provide an improved process for the preparation of stable and bioavailable anti-tubercular pharmaceutical composition of fixed dose combination of all four first line anti-tubercular drugs viz. rifampicin, isoniazid, pyrazinamide and ethambutol hydrochloride using a wet granulation manufacturing process to formulate varying strengths of the said drugs in fixed dose combination composition
- an improved process for the preparation of an antitubercular pharmaceutical composition in fixed dose combination containing four drugs rifampicin, isoniazid, pyrazinamide and ethambutol hydrochloride comprising, a) mixing rifampicin with excipients followed by wet granulation of resulting mixture with a binder material to obtain granules of said mixture and thereafter subjecting the said granules to drying; b) mixing isoniazid with excipients followed by wet granulation of resulting mixture with a binder material to obtain granules of said mixture and thereafter subjecting the said granules to drying, c) mixing pyrazinamide with excipients followed by wet granulation of resulting mixture with a binder material to obtain granules of said mixture and thereafter subjecting the said granules to drying; d) mixing ethambutol hydrochloride with excipients followed by wet
- an improved process for the preparation of an antitubercular pharmaceutical composition in fixed dose combination containing four drugs rifampicin, isoniazid, pyrazinamide and ethambutol hydrochloride comprising; a) mixing rifampicin with excipients followed by wet granulation of resulting mixture with a binder material to obtain granules of said mixture and thereafter subjecting the said granules to drying; b) mixing isoniazid and pyrazinamide with excipients followed by wet granulation of resulting mixture with a binder material to obtain granules of said mixture and thereafter subjecting the said granules to drying; c) mixing ethambutol hydrochloride with excipients followed by wet granulation of resulting mixture with a binder material to obtain granules of said mixture and thereafter subjecting the said granules to drying; d) mixing the granules obtained in
- Figure 1 is a graph illustrating the dissolution profile of rifampicin from compositions prepared using 2-step, 3-step and 4-step granulation without use of a surfactant.
- Figure 2 is a graph illustrating the dissolution profile of rifampicin from composition with and without surfactant, sodium lauryl sulfate (SLS) prepared by a 3-step granulation process
- Figure 3 is a graph illustrating the comparative release of rifampicin in-vivo over time for compositions prepared by 2-step and 3-step granulation process
- the invention relates to an improved process for preparation of a composition
- a composition comprising fixed dose combination (FDC) of four anti-tubercular drugs viz rifampicin, isoniazid, pyrazinamide and ethambutol hydrochloride which improves the dissolution of poorly soluble drug rifampicin and hence improve its bioavailability without the use of surfactants.
- FDC fixed dose combination
- the four anti-TB drugs are granulated using a 3-step wet granulation process wherein rifampicin is granulated separately, isoniazid and pyrazinamide are granulated together and ethambutol is granulated separately
- the four anti-TB drugs are granulated using a 4-step wet granulation process, wherein rifampicin, isoniazid, pyrazinamide and ethambutol hydrochloride are granulated separately.
- the 4-step granulation process comprises a) mixing rifampicin with excipients followed by wet granulation of resulting mixture with a binder material to obtain granules of said mixture and thereafter subjecting the said granules to drying; b) mixing isoniazid with excipients followed by wet granulation of resulting mixture with a binder material to obtain granules of said mixture and thereafter sub j ecting the said granules to drying; c) mixing pyrazinamide with excipients followed by wet granulation of resulting mixture with a binder material to obtain granules of said mixture and thereafter subjecting the said granules to drying; d) mixing ethambutol hydrochloride with excipients followed by wet granulation of resulting mixture with a binder material to obtain granules of said mixture and thereafter subjecting the said granules to drying; e) mixing the granules
- the 3-step granulation process comprises a) mixing rifampicin with excipients followed by wet granulation of resulting mixture with a binder material to obtain granules of said mixture and thereafter subjecting the said granules to drying; b) mixing isoniazid and pyrazinamide with excipients followed by wet granulation of resulting mixture with a binder material to obtain granules of said mixture and thereafter subjecting the said granules to drying; c) mixing ethambutol hydrochloride with excipients followed by wet granulation of resulting mixture with a binder material to obtain granules of said mixture and thereafter subjecting the said granules to drying; d) mixing the granules obtained in steps a), b) and c) with excipients to obtain a lubricated blend e) converting the resulting lubricated blend into a solid dosage form
- the solid dosage forms obtained according to the process of present invention may be tablets or capsules or granules.
- the tablets may be obtained by compression of the resultant granules after lubrication and the compressed tablets may be film coated. But when capsules are chosen as the dosage form the granules can be used as such or granules can be used to prepare a suspension.
- the excipients, which can be used in the process of the present invention besides binder materials include one or more of antioxidants, inert diluents, disintegrants and conventional additives such as lubricating agents or coating agents but not surfactants
- the inert diluents which can be used in the process of the present invention include calcium carbonate, calcium sulfate, dextrates, dibasic calcium phosphate, magnesium carbonate, magnesium oxide, lactose, mannitol, microcrystalline cellulose, starch, polymethacrylates and the like
- the preferred diluents are microcrystalline cellulose, lactose, dibasic calcium phosphate and starch
- antioxidants which can be used in the process of the present invention include sodium metabisulphite, sodium sulphite, ⁇ -tocopherol, ascorbic acid, sodium ascorbate, malic acid, propylgallate and the like
- the preferred antioxidants are ascorbic acid and sodium ascorbate
- antioxidant used is ascorbic acid in the range of 0 1 to 1 5 wt % of the total composition, preferably in the range of 0.1 to 1 wt %
- the binder materials which can be used in the process of the present invention include gelatin, starch, povidone, hydroxypropylmethyi cellulose, hydroxypropyl cellulose, pregelatinized starch, sucrose, acacia, alginic acid, sodium alginate and the like
- the preferred binder materials are pregelatinised starch, povidone and gelatin
- the binder material or mixtures thereof may be present in the range of 1 to 20 wt % of the total composition, preferably in the range of 2 to 15 wt %.
- Pregelatinised Starch is partially gelatinised starch
- the binder solution prepared from a partially gelatinised starch is much more consistent in binding properties as compared to fully gelatinised starch
- the partially gelatinised starch has multi-functional advantages, it is used as a binder, disintegrant, flow aid, lubricant, it also enhances formulation flexibility by complementing functionality of other excipients It is known to facilitate the wetting, particularly of hydrophobic drugs and thus significantly affecting subsequent drug dissolution
- pregelatinised starch is used as a binder in the range of 1 to 15 wt % of the total composition, preferably in the range of 3 to 12 wt %
- gelatin is used as a binder in the range of 0 2 to 2 wt % of the total composition, preferably in the range of 0 3 to 1 wt %
- povidone is used as a binder in the range of 0 2 to 5 wt % of the total composition, preferably in the range of 0 3 to 4 wt %.
- the lubricating agents which can be used in the process of the present invention include magnesium stearate, calcium stearate, stea ⁇ c acid, colloidal silicon dioxide, hydrogenated vegetable oil and the like.
- the preferred lubricating agents are colloidal silicon dioxide and magnesium stearate.
- the disintegrants, which can be used in the process of the present invention include crospovidone, sodium starch glycollate, croscarmellose sodium, microcrystalline cellulose and the like.
- the preferred disintegrants are crospovidone and sodium starch glycollate
- Crospovidone is added in rifampicin granulation and at lubrication stage before compression It helps in reducing the disintegration time and thereby improves dissolution of rifampicin Crospovidone provides porous capillary network for penetration of water and thus reduces disintegration time of the composition
- disintegrant used is crospovidone in the range of 1 to 10 wt % of the total composition, preferably it is in the range of 2 to 8 wt %
- the granules obtained by wet granulation with a binder material are dried at a temperature between 40° C to 80° C, preferably between 50° C to 70° C
- the coating agents which can be used in the process of the present invention include hydroxypropyl methylcellulose, polyvinyl alcohol, ethyl cellulose, methacrylic acid copolymers, cellulose acetate phthalate, cetyl alcohol, shellac, microcrystalline wax, Opadry AMB and the like
- the preferred coating agent is Opadry AMJB
- Figure 1 shows the result obtained when all the three compositions i e by 2-step granulation, 3-step granulation and 4-step granulation prepared without using a surfactant, were studied for m-vitro release It was clearly evident that the 2-step granulation formulation was inferior compared to 3-step and 4-step granulation The 3 and 4-step granulated compositions were comparable
- compositions in a form suitable for oral administration, i.e. as tablets or capsules.
- dosage units preferably contain 60 to 600 mg rifampicin, 100 to 1000 mg ethambutol hydrochloride, 30 to 300 mg isoniazid and
- A) 3-Step Granulation Process Rifampicin, microcrystalline cellulose or lactose, crospovidone and pregelatinized starch or povidone were mixed. Ascorbic acid was dissolved in water and then pregelatinized starch dispersed in water or povidone (polyvinyl pyrrolidone K-30) was dissolved in water to make a binder solution. The blend was granulated with the binder solution.
- Isoniazid, pyrazinamide, microcrystalline cellulose or lactose were mixed.
- the blend was granulated with pregelatinized starch dispersed in water or povidone (polyvinyl pyrrolidone K-30) dissolved in water.
- Ethambutol hydrochloride and microcrystalline cellulose or dicalcium phosphate were mixed and granulated with gelatin solution. After drying, the granules of all 3-steps were blended together and mixed with silicon dioxide, microcrystalline cellulose, crospovidone or sodium starch glycollate and magnesium stearate. The granules were compressed into tablets and coated with Opadry AMB Brown, which is a readymade coating composition manufactured by Colorcon Asia Ltd., India; which consists of polyvinyl alcohol, titanium dioxide, talc, lecithin, xanthan gum and iron oxide colorant.
- Pyrazinamide optionally by mixing with lactose was granulated with pregelatinized starch dispersed in water or povidone (polyvinyl pyrolidone K30) dissolved in water, separately
- Ethambutol Hydrochloride and microcrystalline cellulose or dicalcium phosphate were mixed and granulated with gelatin solution After drying, the granules of all 4-steps were blended together and mixed with silicon dioxide, microcrystalline cellulose, crospovidone or sodium starch glycollate and magnesium stearate The granules were compressed into tablets and coated with Opadry AMB Brown
Abstract
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Priority Applications (2)
Application Number | Priority Date | Filing Date | Title |
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PCT/IN2001/000093 WO2002087547A1 (en) | 2001-04-27 | 2001-04-27 | An improved process for preparation of four-drug anti-tubercular fixed dose combination |
BR0116994-7A BR0116994A (en) | 2001-04-27 | 2001-04-27 | An improved process for preparing a composition comprising a fixed dose combination (fdc) of four antituberculosis drugs |
Applications Claiming Priority (1)
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PCT/IN2001/000093 WO2002087547A1 (en) | 2001-04-27 | 2001-04-27 | An improved process for preparation of four-drug anti-tubercular fixed dose combination |
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PCT/IN2001/000093 WO2002087547A1 (en) | 2001-04-27 | 2001-04-27 | An improved process for preparation of four-drug anti-tubercular fixed dose combination |
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WO (1) | WO2002087547A1 (en) |
Cited By (20)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005046567A2 (en) * | 2003-09-10 | 2005-05-26 | Meena Shelgaonkar | Synergistic formulation of antioxidants and antimycobacterial agents: a method of making the same |
WO2005074937A1 (en) * | 2004-02-04 | 2005-08-18 | Vinay Ramakant Sapte | Oral cyclodextrin complexes of anti-tuberculosis drug |
WO2005107740A1 (en) * | 2004-05-07 | 2005-11-17 | Vinay Ramakant Sapte | Enhancing the efficacy of tubercular drugs by combination with alpha tocopherol |
WO2005107741A1 (en) * | 2004-05-07 | 2005-11-17 | Vinay Ramakant Sapte | Novel oral compositions comprising antitubercular drugs in combination with alpha-tocopherol |
WO2012013756A2 (en) | 2010-07-28 | 2012-02-02 | Laboratoires Pharma 5 | Method for preparing tablets combining rifampicin, isoniazid, pyrazinamide and, optionally, ethambutol |
FR2963236A1 (en) * | 2010-07-28 | 2012-02-03 | Pharma 5 Lab | Preparing composition containing e.g. rifampicin, and optionally ethambutol, comprises wet granulation of isoniazid, pyrazinamide and optionally ethambutol by wetting with binder in solvent, drying and adding rifampicin |
WO2011132114A3 (en) * | 2010-04-20 | 2012-03-22 | Joint Stock Company "Pharmasyntez" | Tuberculosis drug based on 4-thioureido-iminomethylpyridinium perchlorate: method of preparation and treatment |
CN102579447A (en) * | 2011-12-31 | 2012-07-18 | 沈阳药科大学 | Preparation method for anti-tuberculosis medicinal compound preparation |
CN102920707A (en) * | 2012-11-02 | 2013-02-13 | 沈阳药科大学 | Process for preparing compound antituberculous preparation |
US8470365B2 (en) | 2010-07-29 | 2013-06-25 | Taiwan Biotech Co., Ltd. | Process for preparation of anti-tubercular combination and pharmaceutical composition prepared therefrom |
US8604222B2 (en) | 2004-07-30 | 2013-12-10 | Forest Laboratories Holdings Limited | Nebivolol and its pharmaceutically acceptable salts, process for preparation and pharmaceutical compositions of nebivolol |
US20140127294A1 (en) * | 2011-04-12 | 2014-05-08 | Zhejiang Hisun Pharmaceutical Co., Ltd. | Oral solid formulation of compound anti-tubercular drug and preparation method thereof |
WO2015011163A1 (en) * | 2013-07-26 | 2015-01-29 | Sanofi | Antitubercular composition comprising rifampicin, isoniazid, ethambutol and pyrazinamide and its process of preparation. |
CN104706638A (en) * | 2015-02-04 | 2015-06-17 | 上海华源安徽仁济制药有限公司 | Compound rifampin capsules and preparation method thereof |
US20160158157A1 (en) * | 2013-07-26 | 2016-06-09 | Sanofi | Anti-tuberculosis stable pharmaceutical composition in a form of a coated tablet comprising granules of isoniazid and granules of rifapentine and its process of preparation |
US9814680B2 (en) | 2013-07-26 | 2017-11-14 | Sanofi | Anti-tuberculosis stable pharmaceutical composition in a form of a dispersible tablet comprising granules of isoniazid and granules of rifapentine and its process of preparation |
CN110169954A (en) * | 2019-06-20 | 2019-08-27 | 江苏四环生物制药有限公司 | It is a kind of to dissolve out stable pyrazinamide tablet and preparation method thereof |
CN110200933A (en) * | 2019-07-11 | 2019-09-06 | 重庆华邦制药有限公司 | It is used to prepare the composition and its preparation method and application for treating phthisical three compound preparation |
EP3578167A1 (en) * | 2018-06-04 | 2019-12-11 | Universitat de Barcelona | Suspension formulation for the treatment of tuberculosis |
CN113694067A (en) * | 2021-09-30 | 2021-11-26 | 齐齐哈尔医学院 | Microsphere sustained-release preparation loaded with isoniazid and rifampicin and preparation method thereof |
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2001
- 2001-04-27 WO PCT/IN2001/000093 patent/WO2002087547A1/en active Application Filing
- 2001-04-27 BR BR0116994-7A patent/BR0116994A/en not_active Application Discontinuation
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EP0398165A1 (en) * | 1989-05-19 | 1990-11-22 | Fatol Arzneimittel Gmbh | Combination preparations containing rifampicin and thioacetazone and eventually isoniazide or ethambutol as active agents |
BE1010972A6 (en) * | 1996-10-09 | 1999-03-02 | Lupin Lab Ltd | Pharmaceutical anti-tuberculosis composition and method intended to produce said composition |
Cited By (37)
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---|---|---|---|---|
WO2005046567A2 (en) * | 2003-09-10 | 2005-05-26 | Meena Shelgaonkar | Synergistic formulation of antioxidants and antimycobacterial agents: a method of making the same |
WO2005046567A3 (en) * | 2003-09-10 | 2005-09-22 | Meena Shelgaonkar | Synergistic formulation of antioxidants and antimycobacterial agents: a method of making the same |
WO2005074937A1 (en) * | 2004-02-04 | 2005-08-18 | Vinay Ramakant Sapte | Oral cyclodextrin complexes of anti-tuberculosis drug |
WO2005107740A1 (en) * | 2004-05-07 | 2005-11-17 | Vinay Ramakant Sapte | Enhancing the efficacy of tubercular drugs by combination with alpha tocopherol |
WO2005107741A1 (en) * | 2004-05-07 | 2005-11-17 | Vinay Ramakant Sapte | Novel oral compositions comprising antitubercular drugs in combination with alpha-tocopherol |
US8633241B2 (en) | 2004-07-30 | 2014-01-21 | Forest Laboratories Holdings, Limited | Nebivolol and its pharmaceutically acceptable salts, process for preparation and pharmaceutical compositions of nebivolol |
US8604222B2 (en) | 2004-07-30 | 2013-12-10 | Forest Laboratories Holdings Limited | Nebivolol and its pharmaceutically acceptable salts, process for preparation and pharmaceutical compositions of nebivolol |
EA023213B1 (en) * | 2010-04-20 | 2016-05-31 | Открытое Акционерное Общество "Фармасинтез" | Tuberculosis drug based on 4-thioureido-iminomethylpyridinium perchlorate, method of preparation and treatment |
WO2011132114A3 (en) * | 2010-04-20 | 2012-03-22 | Joint Stock Company "Pharmasyntez" | Tuberculosis drug based on 4-thioureido-iminomethylpyridinium perchlorate: method of preparation and treatment |
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