EP1711182A1 - Orale cyclodextrin-komplexe von antituberkulose-mitteln - Google Patents
Orale cyclodextrin-komplexe von antituberkulose-mittelnInfo
- Publication number
- EP1711182A1 EP1711182A1 EP04806723A EP04806723A EP1711182A1 EP 1711182 A1 EP1711182 A1 EP 1711182A1 EP 04806723 A EP04806723 A EP 04806723A EP 04806723 A EP04806723 A EP 04806723A EP 1711182 A1 EP1711182 A1 EP 1711182A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- rifampicin
- drugs
- composition
- scc
- isoniazid
- Prior art date
- Legal status (The legal status 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 status listed.)
- Withdrawn
Links
- 229940072185 drug for treatment of tuberculosis Drugs 0.000 title description 11
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical class O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 title description 2
- 229960001225 rifampicin Drugs 0.000 claims abstract description 41
- JQXXHWHPUNPDRT-WLSIYKJHSA-N rifampicin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC=2C(O)=C3C([O-])=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CC[NH+](C)CC1 JQXXHWHPUNPDRT-WLSIYKJHSA-N 0.000 claims abstract description 41
- AEUTYOVWOVBAKS-UWVGGRQHSA-N ethambutol Chemical compound CC[C@@H](CO)NCCN[C@@H](CC)CO AEUTYOVWOVBAKS-UWVGGRQHSA-N 0.000 claims abstract description 38
- QRXWMOHMRWLFEY-UHFFFAOYSA-N isoniazide Chemical compound NNC(=O)C1=CC=NC=C1 QRXWMOHMRWLFEY-UHFFFAOYSA-N 0.000 claims abstract description 22
- 229960003350 isoniazid Drugs 0.000 claims abstract description 21
- 229960005206 pyrazinamide Drugs 0.000 claims abstract description 21
- IPEHBUMCGVEMRF-UHFFFAOYSA-N pyrazinecarboxamide Chemical compound NC(=O)C1=CN=CC=N1 IPEHBUMCGVEMRF-UHFFFAOYSA-N 0.000 claims abstract description 21
- 229960000285 ethambutol Drugs 0.000 claims abstract description 17
- 239000000843 powder Substances 0.000 claims abstract description 16
- 201000008827 tuberculosis Diseases 0.000 claims abstract description 11
- 230000000845 anti-microbial effect Effects 0.000 claims abstract description 4
- 239000000203 mixture Substances 0.000 claims description 52
- 238000000034 method Methods 0.000 claims description 23
- 235000000346 sugar Nutrition 0.000 claims description 16
- 239000004599 antimicrobial Substances 0.000 claims description 12
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 3
- 229940049413 rifampicin and isoniazid Drugs 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 49
- 229940079593 drug Drugs 0.000 abstract description 49
- 238000002156 mixing Methods 0.000 abstract description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 11
- 238000002560 therapeutic procedure Methods 0.000 abstract description 9
- 239000008202 granule composition Substances 0.000 abstract description 7
- 235000011389 fruit/vegetable juice Nutrition 0.000 abstract description 5
- 239000011521 glass Substances 0.000 abstract description 5
- 229940042126 oral powder Drugs 0.000 abstract description 4
- 229940000425 combination drug Drugs 0.000 description 24
- 239000003826 tablet Substances 0.000 description 20
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- 101100240606 Caenorhabditis elegans scc-2 gene Proteins 0.000 description 6
- 206010059866 Drug resistance Diseases 0.000 description 6
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- 229920002678 cellulose Polymers 0.000 description 4
- -1 d- glucopyranosyl unit Chemical group 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 229960001618 ethambutol hydrochloride Drugs 0.000 description 4
- 230000036541 health Effects 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
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- 201000009671 multidrug-resistant tuberculosis Diseases 0.000 description 3
- 230000008520 organization Effects 0.000 description 3
- 238000009097 single-agent therapy Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- 101100532685 Caenorhabditis elegans scc-3 gene Proteins 0.000 description 2
- 229920000858 Cyclodextrin Polymers 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 229940124976 antitubercular drug Drugs 0.000 description 2
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical class OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 2
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
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- 238000005469 granulation Methods 0.000 description 2
- 230000003179 granulation Effects 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 239000000814 tuberculostatic agent Substances 0.000 description 2
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
- 101100532684 Arabidopsis thaliana SCC3 gene Proteins 0.000 description 1
- 102100035590 Cohesin subunit SA-1 Human genes 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 101100043640 Homo sapiens STAG1 gene Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 206010062207 Mycobacterial infection Diseases 0.000 description 1
- 101100062195 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) CPR4 gene Proteins 0.000 description 1
- 101100532687 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) IRR1 gene Proteins 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 206010066901 Treatment failure Diseases 0.000 description 1
- 208000036981 active tuberculosis Diseases 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000002365 anti-tubercular Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 230000003385 bacteriostatic effect Effects 0.000 description 1
- 239000001202 beta-cyclodextrine Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- MIFVTYPADKEWAV-HGRQBIKSSA-N chembl407030 Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)OC3O[C@H](CO)C([C@@H]([C@H]3O)O)C3O[C@H](CO)C([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)C3O[C@@H]1CO MIFVTYPADKEWAV-HGRQBIKSSA-N 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229920006037 cross link polymer Polymers 0.000 description 1
- 238000007922 dissolution test Methods 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 208000015355 drug-resistant tuberculosis Diseases 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000002389 essential drug Substances 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000001050 lubricating effect Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000036457 multidrug resistance Effects 0.000 description 1
- 208000027531 mycobacterial infectious disease Diseases 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- SRVJKTDHMYAMHA-WUXMJOGZSA-N thioacetazone Chemical compound CC(=O)NC1=CC=C(\C=N\NC(N)=S)C=C1 SRVJKTDHMYAMHA-WUXMJOGZSA-N 0.000 description 1
- 210000000115 thoracic cavity Anatomy 0.000 description 1
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
- A61K31/13—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
- A61K31/435—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
- A61K31/33—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
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
- A61P31/06—Antibacterial agents for tuberculosis
Definitions
- the invention relates to oral powder / granule compositions comprising upto 4 anti-TB drugs used in the short Course Chemotherapy (SCC) namely Rifampicin, Isoniazid, Ethambutol and Pyrazinamide (SCC-4), in palatable powder form, which can be consumed by mixing the powder in a glass of water or juice with meal.
- SCC short Course Chemotherapy
- This invention further relates to oral/ powder/ granule compositions of two (SCC-2), three (SSC-3) and four (SCC-4) anti-TB drugs for short course chemotherapy (SCC).
- Tuberculosis is one of the most common infectious diseases known to man. About 32% of the world's population is infected with TB. Every year, approximately 8 million of these infected people develop active TB and almost 2 million of these will die from the disease. In India alone, one person dies of TB every minute.
- WHO World Health Organization
- anti-tuberculosis drugs can be given as single drug formulations or as fixed dose combinations (FDCs) where two or more anti-tuberculosis drugs are present in fixed proportions in the same formulation.
- WHO and IUATLD advocate the replacement of single drug preparations by FDC tablets as the primary treatment for tuberculosis.
- the disadvantage of the 4 FDC tablets is that, if the patient does not take all the tablets i.e. three or four as recommended at a time, as per the body weight the dose becomes sub-optimal and there is then the risk of developing the MDR TB
- FDC tablets gives with poor rifampicin bioavailability means giving inadequate therapy, without even being aware of it. Consequently, using FDC tablets of poor rifampicin bioavailability could directly lead to poor treatment outcome and may create, and not prevent, drug resistance.
- Good quality FDC tablets with demonstrated bioavailability of rifampicin is- an absolute requirement for successful treatment outcomes in programmes utilizing FDC-based regimens.
- Ethambutol hydrochloride which is a highly hygroscopic material, tends to catalyze rifampicin and isoniazid interaction.
- Ethambutol hydrochloride which is a highly hygroscopic material, tends to catalyze rifampicin and isoniazid interaction.
- 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 behavior.
- 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.
- 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.
- the invented composition in powder / granule/ pellet forms packed in pouches / sachets eliminates all the problems and the process requirements of wet granulation, drying, mixing & lubricating with surfactant and compressing the tablets.
- the invented product avoids the need for coating of the product.
- the object of present invention is to provide complex each of the active drugs with agents such as Hydroxypropyl Methyl Cellulose, Ethyl Cellulose, starches or cellulosins or Schardinger sugars, which will encapsulate the particles of the Active Drug. When mixed together after such a treatment these drugs will not react with each other. Also the process of complexation is such that it helps in the better dissolution of the drug which is not easily soluble like rifampicin. Such complexation also reduces the absorption of moisture in highly hygroscopic materials like Ethambutol Hudrochloride.
- Another object of present invention is to formulate the exact quantity of dosage required in one single sachet pouch thereby avoiding less than or more than optimal dosage.
- Another object of the present invention was to prepare the powder in such a way that after mixing in water it will be palatable for the patient.
- the invented powder composition in a Sachet or pouch form has following advantages.
- Oral powder / granule compositions comprising upto 4 anti-TB drugs used in the short Course Chemotherapy (SCC) namely Rifampicin, Isoniazid, Ethambutol and Pyrazinamide (SCC-4), in palatable powder form, which can be consumed by mixing the powder in a glass of water or juice with meal is disclosed.
- SCC short Course Chemotherapy
- SCC-4 Rifampicin, Isoniazid, Ethambutol and Pyrazinamide
- This invention further discloses oral / powder / granule compositions of two (SCC-2), three (SSC-3) and four (SCC-4) anti-TB drugs for short course chemotherapy (SCC).
- the present invention discloses Oral powder / granule compositions comprising upto 4 anti-TB drugs used in the short Course Chemotherapy (SCC) namely Rifampicin, Isoniazid, Ethambutol and Pyrazinamide (SCC-4), in palatable powder form, which can be consumed by mixing the powder in a glass of water or juice with meal. Further oral / powder / granule compositions of two (SCC-2), three (SSC-3) and four (SCC-4) anti- TB drugs for short course chemotherapy (SCC) are also disclosed.
- SCC powder composition of the Anti-tubercular drugs namely Rifampicin (R), Isoniazid ( H ), Pyrazinamide ( Z ) and Ethambutol ( E ) Hydrochloride packed into a pouch / sachet comprises;
- Figure I illustrates comparative in-vitro bioavailability study of Rifampicin in SCC-4 composition of the present invention and SCC-4 tablet of FDC.
- No 1 indicates in-vitro bioavailability of rifampicin in SCC-4 composition.
- In-vitro bioavailability of rifampicin in SCC-4 tablet of FDC is shown by No. 2.
- X-axis No. 3 is time in minutes against Y axis (No. 4) is percentage of in-vitro bioavailable of rifampicin in the fig I.
- Figure II illustrates comparative in-vitro bioavailability study of Pyrazinamide in SCC-4 composition of the present invention and SCC-4 tablet of FDC.
- In-vitro bioavailability of Pyrazinamide is showned by No.5 and No. 6 in SCC-4 composition and SCC-4 tablet of FDC.
- X-axis (7) represents time in minute
- Y-axis (8) is representing percentage of in-vitro bioavailability of pyrazinamide in SCC-4 composition and SCC-4 tablet of FDC.
- Figure III illustrates comparative in-vitro bioavailability study of Isoniazid in SCC-4 composition of the present invention and SCC-4 tablet of FDC.
- No. 9 and 10 indicates in-vitro bioavailability of isoniazid in SCC-4 composition of the present invention and SCC-4 tablet of FDC.
- X -axis (11) represents the time in minute while Y-axis (12) represents percentage of in-vitro bioavailability of isoniazid in SCC-4 composition and SCC-4 tablet of FDC.
- anti-microbial encompasses, e.g., bactericidal, bacteriostatic, fungicidal, and antiviral compounds.
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Pulmonology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN124MU2004 | 2004-02-04 | ||
| PCT/IN2004/000178 WO2005074937A1 (en) | 2004-02-04 | 2004-06-18 | Oral cyclodextrin complexes of anti-tuberculosis drug |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP1711182A1 true EP1711182A1 (de) | 2006-10-18 |
Family
ID=34835543
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP04806723A Withdrawn EP1711182A1 (de) | 2004-02-04 | 2004-06-18 | Orale cyclodextrin-komplexe von antituberkulose-mitteln |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP1711182A1 (de) |
| BR (1) | BRPI0415338A (de) |
| UA (1) | UA44385U (de) |
| WO (1) | WO2005074937A1 (de) |
| ZA (1) | ZA200600783B (de) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MD3942C2 (ro) * | 2009-01-22 | 2010-02-28 | Институт Химии Академии Наук Молдовы | Complecşi ai fierului şi cobaltului cu acidul furan-2-carboxilic cu proprietăţi antituberculoase |
| WO2012013756A2 (fr) | 2010-07-28 | 2012-02-02 | Laboratoires Pharma 5 | Procédé de préparation de comprimés contenant en association la rifampicine, l'isoniazide, la pyrazinamide, et éventuellement l'ethambutol |
| US9814711B2 (en) * | 2013-07-26 | 2017-11-14 | Sanofi | Antitubercular composition comprising rifampicin, isoniazid, ethambutol and pyrazinamide and its process of preparation |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH02300140A (ja) * | 1989-05-12 | 1990-12-12 | Yamanouchi Pharmaceut Co Ltd | 薬物のシクロデキストリン包接体及びその製造法 |
| CN1029080C (zh) * | 1992-06-26 | 1995-06-28 | 佛冈县新技术研究开发部 | 利福平软膏的配制方法 |
| BR0116994A (pt) * | 2001-04-27 | 2004-03-02 | Lupin Ltd | Um processo aperfeiçoado para a preparação de uma composição que abrange uma combinação de dose fixa (fdc) de quatro drogas antituberculose |
| US7001893B2 (en) * | 2002-10-28 | 2006-02-21 | Council Of Scientific And Industrial Research | Inclusion complex of Rifampicin, an anti-tubercular drug, with β-cyclodextrin or 2-hydroxypropyl β-cyclodextrin and a process thereof |
-
2004
- 2004-06-18 EP EP04806723A patent/EP1711182A1/de not_active Withdrawn
- 2004-06-18 BR BRPI0415338-3A patent/BRPI0415338A/pt not_active Application Discontinuation
- 2004-06-18 WO PCT/IN2004/000178 patent/WO2005074937A1/en not_active Ceased
- 2004-06-18 UA UAA200600347U patent/UA44385U/ru unknown
-
2006
- 2006-01-03 ZA ZA200600783A patent/ZA200600783B/xx unknown
Non-Patent Citations (1)
| Title |
|---|
| See references of WO2005074937A1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| BRPI0415338A (pt) | 2006-12-05 |
| ZA200600783B (en) | 2007-02-28 |
| WO2005074937A1 (en) | 2005-08-18 |
| UA44385U (en) | 2009-10-12 |
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