Leave a Reply Cancel reply Your email address will not be published. Required fields are marked. Name: Email: Website: Message: You may use these HTML tags and attributes: a href" title" abbr title" acronym title" b blockquot; cite" cite code del datetime" em i q cite" strike strong.There is a possibility to carry out further modifications in the CD molecule with suitable substitutions. For example in case of heptakis-2,6-di-0-methyl-CD (DIMEB ) two hydroxyl groups of every glucose unit are methylated, while in case of randomly methylated -CD (RAMEB ) the hydroxy groups are substituted randomly by methoxy groups, however the average degree.
(Levothyroxine and Liothyronine) T Man, Thailand Thiroyd Greater Pharma, Thailand Thyreotom Forte (Levothyroxine and Liothyronine) Berlin-Chemie, Czech Republic Thyro-4 Faran, Tunisia Thyroid-S Sriprasit Pharma, Thailand Thyrox Renata, Bangladesh Tirogal Bioquifar, Colombia Tiroideibsa (Levothyroxine and Liothyronine) IBSA Farmaceutici Italia, Italy Tiroxin Metlen, Ecuador Bagothyrox Cimica Montpelier, Georgia Berlthyrox Berlin-Chemie AG, Vietnam Combithyrex forte (Levothyroxine and Liothyronine).As can be concluded from the above data, among the studied unsubstituted cyclodextrins the -cyclodextrin was found to improve the aqueous solubility of L-thyroxine sodium most remarkably, thus to have the highest affinity towards the drug.
It has unexpectedly been found that among the highly watersoluble -cyclodextrin derivatives methylated-cyclodextrins (both randomly methylated and heptakis 2,6-di-O-methyl-cyclodextrins) appear to be less potent solubilizers of thyroxine, than the chemically non-modified -cyclodextrin.Germany Levothyroxine (Thyroxine). L- Thyrox Hexal 50Mcg Tablets Strength value: 0.05/mg Dosage Form:. Store below 25C Manufacturer Name: Hexal.
A thyroidal pharmaceutical composition according to the invention can be provided for the treatment of hypothyroidism. Further, a thyroidal pharmaceutical composition according to the invention can be characterized in that the composition is a transdermal therapeutical system (TTS) comprising a reservoir containing a hydrogel.According to an alternative method, the thyroxine and cyclodextrins can be kneaded in the presence of small amounts of water. The thyroxine/-cyclodextrin complexes can be used for the preparation of common pharmaceutical dosage forms like tablets, gels, ointments, cremes, injectables, suppositories, patches and plasters.
In no case it has been published that the chemically non-modified, so-called parent -cyclodextrin - at identical cyclodextrin concentration - results in a more than 2.5-fold solubility enhancement as compared with the best solubilizer known, the heptakis-(2,6-di-0-methyl)-cyclodextrin (Pitha, J.USA) was added. The mixture was ultrasonicated for 10 minutes and stirred for 3 hours to obtain a slight opalescent hydrogel. The stability of the hydrogel according to example 4 was found to be satisfactory over a storage period of two weeks at 25 C Neither any precipitatio.
The following examples serve for illustration and do not limit the present invention. 20 ml of a 10 aqueous '-CD solution was intensively stirred at room temperature and to this solution 500 mg of L-thyroxine-Na is added without any solvent.The reaction mixture was further stirred for 12 hours at room temperature with 600 r.p.m. The resulting slightly opalescent solution was then freeze dried yielding 2.28 g of white, nearly amorphous solid that has a thyroxine content of 20.12 by weight.
Finally, a thyroidal pharmaceutical composition according to the invention can be characterized by a gel forming agent based on a polyacrylic acid or derivatives thereof. One evidence of the interaction between L-thyroxine and cyclodextrins is that the cyclodextrins increase the aqueous solubility of the thyroxine as shown in Table 1.Puntanos, Argentina Levotiroxina Sdica Refasa, Peru Levotiroxina Sodica American Generics American Generics, Colombia Levotiroxina Sodica Andromaco Andromaco, Chile Levotiroxina Sodica. Chile, Chile Levotiroxina Sdica Ratiopharm Ratiopharm, Portugal Levotrin GlaxoSmithKline, Argentina Levoxyl King Pharmaceuticals, United States L-T Craveri, Argentina L-Thyrox HEXAL Hexal, Germany L-Thyrox Jod HEXAL (Levothyroxine and Potassium Iodide) Hexal, Germany L-Thyroxin Berlin-Chemie, Romania; Berlin-Chemie.
It is further demonstrated that 2-hydroxypropylated -cyclodextrin (HPBCD ) and maltosyl-cyclodextrin have shown not to be really feasible solubilizing agents for thyroxine, since they did not significantly improve the aqueous solubility of thyroxine even at higher applied concentrations.The mixture is kneaded for 30 minutes at room temperature to obtain a white cream. The creamy material is dried over P2O5 at room temperature to constant weight. The dry complex is a white or nearly white powder that has a thyroxine content of 10.6 by weight.
Life Sci.). This unexpected experimental finding is the core of the present invention. It is well-known, that -cyclodextrin exhibits the highest aqueous solubility among all parent-cyclodextrins. However, its solutions are physically not stable, because the aqueous solutions of highly purified -cyclodextrins tend to become turbid within days at room temperature, even at 1/5 of the.US matches: UK matches: Scheme. BAN CAS registry number (Chemical Abstracts Service) 000 Chemical Formula C15-H10-I4-N-O4 Molecular Weight 775 Therapeutic Categories. Thyroid hormone Hormone replacement therapy (HRT) Chemical Name. L-Tyrosine, O-(4-hydroxy-3,5-diiodophenyl)-3,5-diiodo- Foreign Names Levothyroxinum (Latin) Levothyroxin (German) Lvothyroxine (French) Generic Names Brand Names Berlthyrox.
A further unexpected observation is that these -cyclodextrin containing aqueous solutions and hydrogels and aqueous gels, resp., remain clear without formation of any solid crystalline or amorphous precipitate. The unexpected excellent physical stability of aqueous thyroxine/-cyclodextrin solutions in the physiologically acceptable pH-range is the other essential feature of our invention, because only the simultaneous prevalence.There is a lot of literature - both publications and patents - which describes the enhancement of poorly soluble drugs with cyclodextrins and with the concomitant consequences, like improved bioavailability, chemical and/or physical stability of the cyclodextrin complexed drug (Szejtli, J.: Cyclodextrin Technology, Kluwer Academic Publ., Dordrecht, Holland, 1988, p.
Further, a formulation according to the invention can be an L-thyroxin sodium/-cyclodextrin formulation. According to another embodiment the invention concerns a process for the production of a formulation according to the invention, wherein the process is characterized be kneading thyroxin and -cyclodextrin in an amount of water which corresponds to the solubility of the formulation.Only in a few cases the -cyclodextrin showed to be as good as a -cyclodextrin derivative. According to one embodiment the invention concerns a transdermal formulation comprising a solution or a hydrogel comprising thyroxin and -cyclodextrin.
Cyclodextrins (CDs) are prepared from starches using CD-glucosyl transferase enzyme. There are three different kinds of CDs, i.e. the, - and -CD, which consists of 6, 7 or 8 glucopyranose units connected with -1.4 glucosidic bonds.Menarini, Lebanon Bitiron (Levothyroxine and Liothyronine) Abdi Ibrahim, Turkey Eferox. Hexal, Oman Eltroxin Glaxo Smithkline, Lebanon Euthroid (Levothyroxine and Liothyronine) Pfizer, Colombia Euthycin Incepta, Bangladesh Euthyrox Merck Kgaa, Lebanon Eutirox Merck, Colombia Lvothyrox Merck Sant, Tunisia Levotiron Abdi Ibrahim, Turkey Levotirox Lafedar Lafedar, Argentina Levotiroxina Colmed Colmed, Colombia L-Thyrox Salutas, Georgia Novothyral (Levothyroxine and Liothyronine).
Redissolution properties of the product according to Example 1: The reconstitution of this lyophilized powder results in a slightly opalescent solution, when 0.1 g of the product is dissolved in 2 ml of distilled water (no solid particles are observed upon standing for two hours).The hydroxyalkylation of cyclodextrins also results in improved aqueous solubility as known for hydroxypropylated and hydroxyethylated cyclodextrine derivatives (Szejtli, J. Cyclodextrin Technology, Kluwer Academic Publ.1988. page 51.). The solubility of these chemically modified cyclodextrins reaches the value of about 400-500 mg/ml at room temperature and their complex-forming capacity also differs from the unsubstituted CDs.
6.48 g (0.005 mole) of -cyclodextrin is wetted with 10 ml of deionized water and intensively grounded for 5 minutes. 0.799 g (0.001 mole) of L-thyroxine-Na is added to the -CD.8 ml of a 70 mg/ml solution of -cyclodextrin was stirred with 142 mg of thyroxine-Na to obtain a clear transparent solution. 150 mg of a water swellable polymer (i.e. Klucel; Hercules Corp.
186-197). Summarizing the available data it can be stated that in most cases the -CD is the best complexing agent for hydrophobic, poorly soluble drugs and among the -cyclodextrins the alkylated (methylated) and the hydroxyalkylated (hydroxypropylated) -cyclodextrins are the most appropriate ones.HEXAL AG (Industriestrasse 25, Holzkirchen, D-83607, DE). with 10 ml of 10 aqueous -cyclodextrin solution containing 300 mg solubilized L-thyroxine-Na.
High concentrations of drug as well as physical stability of the solution and chemical stability of the dissolved drug are the preconditions for an appropriate transdermal thyroxine patch formulation. A formlation according to the invention can be characterized by a molar ratio range of -cyclodextrin: thyroxin of from 25:1 to and preferably 4:1 to 1:1.In some countries, this medicine may only be approved for veterinary use. In the US, Levothyroxine (levothyroxine systemic) is a member of the drug class thyroid drugs and is used to treat Hashimoto's disease, Hypothyroidism - After Thyroid Removal, Myxedema Coma, Thyroid Suppression Test, TSH Suppression and Underactive Thyroid.
Additionally, the aqueous solutions according to the invention can obtain stabilizers, antioxidants, or thickeners like pectins, alginates or silicium dioxides. Hydrogel preparations or aqueous solutions of the complexes may be filled in reservoir patches as described in the prior art.The interaction of thyroxine with cyclodextrins has not yet been reported. Thyroxine/cyclodextrin inclusion complexes as ingredients of any pharmaceutical formulations have never been previously described in any paper or patent. The U.S.
Generic Name: Levothyroxine (Thyroxine) Sodium Trade Name: Euthyrox Strength value: 0.05/mg Dosage Form: Tablet Route of Administration: Oral. ATC Code: H03AA01 Volume: Package type: Tablet container Package size: 100 Legal status: Prescription Product control: Uncontrolled Shelf-life (mon 36.Patent No.4121975 (Ullman, E.; Lavine, F. and Joel, E.) deals with the analytical determination of serum thyroxine levels in patients by competitive protein-binding or immunoassay, employing also -cyclodextrin for the selective removal of interfering components (mainly blood lipids) present in the blood samples.
L- Thyrox Hexal 50Mcg Tablets. Generic Name: Levothyroxine (Thyroxine) Sodium Trade Name: L- Thyrox. Store below 25C Manufacturer Name: Hexal Country Of.Biopharm, Thailand Elthyrone Abbott, Belgium Eltroksin GlaxoSmithKline, Slovenia Eltroxin Alfred Gera, Malta; Amdipharm Mercury, United Kingdom; Aspen, Czech Republic; Aspen, New Zealand; Aspen, Philippines; Aspen, Poland; Aspen Bad Oldesloe, Israel; Aspen Pharmacare, Thailand; Biotoscana, Colombia; GlaxoSmithKline, Bangladesh; GlaxoSmithKline, India; GlaxoSmithKline, Lithuania; GlaxoSmithKline, Oman; GlaxoSmithKline, Singapore; GlaxoSmithKline, Taiwan; GlaxoSmithKline, South Africa; Goldshield, Malta; Invida, Thailand; Mercury.
Film-coated tablet 2.5 Mg, Bid, Oral Patient was hospitalized. (0.07 Mg, Qd, Oral) Hct Hexal (hydrochlorothiazide). L-thyroxine (levothyroxine).L-thyroxine) UK matches: LEVOTHYROXINE 100 MICROGRAMS PER 5ML. LEVOTHYROXINE 25 MICROGRAMS PER 5ML ORAL. L-Thyrox Jod HEXAL (Levothyroxine and Potassium).
Having attained the required clarity of common aqueous solutions, water can be removed from the reaction mixture by known methods, i.e. by freeze-drying or spray drying. In certain cases, when necessary, only a small amount of a suitable, pharmaceutically acceptable organic solvent or detergent can be used as a third component in the formulations.L-thyroxine (levothyroxine Sodium) (levothyroxine Sodium) dosage:. 2011 by a Female patient taking L-thyroxin Hexal (Dosage: Unk). (15 Mg) Insulin; Humira;.