ITMI20101102A1 - PROCESS FOR PREPARING TABLETS WITH CONTROLLED RELEASE - Google Patents
PROCESS FOR PREPARING TABLETS WITH CONTROLLED RELEASE Download PDFInfo
- Publication number
- ITMI20101102A1 ITMI20101102A1 IT001102A ITMI20101102A ITMI20101102A1 IT MI20101102 A1 ITMI20101102 A1 IT MI20101102A1 IT 001102 A IT001102 A IT 001102A IT MI20101102 A ITMI20101102 A IT MI20101102A IT MI20101102 A1 ITMI20101102 A1 IT MI20101102A1
- Authority
- IT
- Italy
- Prior art keywords
- glucosamine
- tablet
- hydrophobic matrix
- salt
- weight
- Prior art date
Links
- 238000013270 controlled release Methods 0.000 title claims description 15
- 238000004519 manufacturing process Methods 0.000 title 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 claims description 40
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 claims description 39
- 229960002442 glucosamine Drugs 0.000 claims description 39
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 32
- 239000011159 matrix material Substances 0.000 claims description 22
- 230000002209 hydrophobic effect Effects 0.000 claims description 18
- 235000019359 magnesium stearate Nutrition 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 15
- 235000021355 Stearic acid Nutrition 0.000 claims description 13
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 13
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 13
- 239000008117 stearic acid Substances 0.000 claims description 13
- 239000000203 mixture Substances 0.000 claims description 12
- MTDHILKWIRSIHB-UHFFFAOYSA-N (5-azaniumyl-3,4,6-trihydroxyoxan-2-yl)methyl sulfate Chemical compound NC1C(O)OC(COS(O)(=O)=O)C(O)C1O MTDHILKWIRSIHB-UHFFFAOYSA-N 0.000 claims description 11
- 229960002849 glucosamine sulfate Drugs 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 8
- 239000006185 dispersion Substances 0.000 claims description 6
- 238000002844 melting Methods 0.000 claims description 5
- 230000008018 melting Effects 0.000 claims description 5
- CBOJBBMQJBVCMW-BTVCFUMJSA-N (2r,3r,4s,5r)-2-amino-3,4,5,6-tetrahydroxyhexanal;hydrochloride Chemical compound Cl.O=C[C@H](N)[C@@H](O)[C@H](O)[C@H](O)CO CBOJBBMQJBVCMW-BTVCFUMJSA-N 0.000 claims description 2
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Natural products CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 claims description 2
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 claims description 2
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Natural products CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 claims description 2
- 239000012458 free base Substances 0.000 claims description 2
- 229960001911 glucosamine hydrochloride Drugs 0.000 claims description 2
- 229950006780 n-acetylglucosamine Drugs 0.000 claims description 2
- 239000008187 granular material Substances 0.000 description 11
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 6
- 238000005303 weighing Methods 0.000 description 5
- 238000005469 granulation Methods 0.000 description 4
- 230000003179 granulation Effects 0.000 description 4
- 239000002245 particle Substances 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 235000010323 ascorbic acid Nutrition 0.000 description 3
- 229960005070 ascorbic acid Drugs 0.000 description 3
- 239000011668 ascorbic acid Substances 0.000 description 3
- 210000000845 cartilage Anatomy 0.000 description 3
- 239000001913 cellulose Substances 0.000 description 3
- 229920002678 cellulose Polymers 0.000 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000011812 mixed powder Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- OKMWKBLSFKFYGZ-UHFFFAOYSA-N 1-behenoylglycerol Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(O)CO OKMWKBLSFKFYGZ-UHFFFAOYSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 229920002567 Chondroitin Polymers 0.000 description 1
- FZHXIRIBWMQPQF-UHFFFAOYSA-N Glc-NH2 Natural products O=CC(N)C(O)C(O)C(O)CO FZHXIRIBWMQPQF-UHFFFAOYSA-N 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000237852 Mollusca Species 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000001361 adipic acid Substances 0.000 description 1
- 229960000250 adipic acid Drugs 0.000 description 1
- 235000011037 adipic acid Nutrition 0.000 description 1
- FZHXIRIBWMQPQF-SLPGGIOYSA-N aldehydo-D-glucosamine Chemical compound O=C[C@H](N)[C@@H](O)[C@H](O)[C@H](O)CO FZHXIRIBWMQPQF-SLPGGIOYSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 229940092738 beeswax Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000004203 carnauba wax Substances 0.000 description 1
- 235000013869 carnauba wax Nutrition 0.000 description 1
- 229940082483 carnauba wax Drugs 0.000 description 1
- DLGJWSVWTWEWBJ-HGGSSLSASA-N chondroitin Chemical compound CC(O)=N[C@@H]1[C@H](O)O[C@H](CO)[C@H](O)[C@@H]1OC1[C@H](O)[C@H](O)C=C(C(O)=O)O1 DLGJWSVWTWEWBJ-HGGSSLSASA-N 0.000 description 1
- 230000037319 collagen production Effects 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 229940049654 glyceryl behenate Drugs 0.000 description 1
- FETSQPAGYOVAQU-UHFFFAOYSA-N glyceryl palmitostearate Chemical compound OCC(O)CO.CCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O FETSQPAGYOVAQU-UHFFFAOYSA-N 0.000 description 1
- 229940046813 glyceryl palmitostearate Drugs 0.000 description 1
- 150000002337 glycosamines Chemical class 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 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 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 230000008407 joint function Effects 0.000 description 1
- 229940057948 magnesium stearate Drugs 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 229960002969 oleic acid Drugs 0.000 description 1
- 235000021313 oleic acid Nutrition 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 229960004274 stearic acid Drugs 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
Classifications
-
- 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
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7008—Compounds having an amino group directly attached to a carbon atom of the saccharide radical, e.g. D-galactosamine, ranimustine
-
- 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
-
- 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
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Molecular Biology (AREA)
- Biophysics (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
†Processo per la preparazione di compresse a rilascio controllato†⠀ Process for the preparation of controlled-release tablets⠀
DESCRIZIONE DESCRIPTION
La presente invenzione riguarda un processo per la preparazione di compresse a rilascio controllato contenenti glucosammina. The present invention relates to a process for the preparation of controlled release tablets containing glucosamine.
La glucosammina à ̈ un prodotto naturale presente nelle conchiglie dei molluschi e nelle ossa e nel midollo osseo degli animali. Glucosamine is a natural product found in the shells of molluscs and in the bones and marrow of animals.
Il nome chimico del composto à ̈ 2-ammino-2-deossi-D-glucosio che corrisponde alla seguente formula The chemical name of the compound is 2-amino-2-deoxy-D-glucose which corresponds to the following formula
H OH H OH
H (I) H (I)
O OR
H O I HAVE
H O H H O H
H H.
NH NH
H<2>OH H <2> OH
La glucosammina à ̈ un amminozucchero precursore di componenti della cartilagine chiamati glucosamminoglicani che stimolano la produzione di collagene. Pertanto la glucosammina protegge dalla perdita di cartilagine nelle articolazioni aiutando a ripristinare le normali funzioni articolari. Glucosamine is an amino sugar precursor of cartilage components called glucosaminoglycans that stimulate collagen production. Therefore glucosamine protects against cartilage loss in the joints by helping to restore normal joint functions.
La somministrazione di glucosammina per via orale à ̈ normalmente utilizzata nel trattamento delle osteoartriti proprio per le sue proprietà di prevenire la degenerazione della cartilagine. The oral administration of glucosamine is normally used in the treatment of osteoarthritis precisely for its properties to prevent cartilage degeneration.
La glucosammina à ̈ rapidamente metabolizzata nel tratto gastrointestinale e pertanto il rilascio controllato di glucosammina presenta diversi vantaggi quali la maggior durata del trattamento terapeutico, la riduzione della variazione dei livelli plasmatici, la diminuzione delle somministrazioni giornaliere e la riduzione dei potenziali effetti collaterali legati ad un picco di concentrazione plasmatica più volte al giorno. Glucosamine is rapidly metabolized in the gastrointestinal tract and therefore the controlled release of glucosamine has several advantages such as a longer duration of therapeutic treatment, a reduction in the variation in plasma levels, a decrease in daily administration and a reduction in the potential side effects associated with a peak plasma concentration several times a day.
La glucosammina à ̈ piuttosto instabile in presenza di umidità perché può facilmente ossidarsi. Glucosamine is quite unstable in the presence of humidity because it can easily oxidize.
Sono note in letteratura diverse formulazioni orali di glucosammina a rilascio controllato. Several controlled release oral formulations of glucosamine are known in the literature.
La domanda di brevetto US 2004/0234599 descrive composizioni a rilascio controllato in cui la glucosammina à ̈ dispersa in una matrice a rilascio controllato costituita da almeno un polimero idrosolubile di cellulosa quale idrossipropilmetilcellulosa, idrossietilcellulosa, idrossipropilcellulosa, carbossimetilcellulosa. US patent application 2004/0234599 describes controlled release compositions in which glucosamine is dispersed in a controlled release matrix consisting of at least one water-soluble cellulose polymer such as hydroxypropylmethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, carboxymethylcellulose.
La domanda di brevetto WO 2008/136016 descrive formulazioni di glucosammina a rilascio controllato comprendenti un nucleo con una matrice polimerica idrofila ed un rivestimento polimerico permeabile pH-indipendente. Patent application WO 2008/136016 discloses controlled release glucosamine formulations comprising a core with a hydrophilic polymer matrix and a pH-independent permeable polymer coating.
Rimane l’esigenza di una composizione orale a rilascio controllato di glucosammina stabile e in grado di garantire un rilascio per un periodo di circa 12 ore. There remains the need for an oral composition with controlled release of glucosamine that is stable and capable of guaranteeing a release for a period of approximately 12 hours.
Abbiamo ora trovato che compresse di glucosammina a rilascio controllato contenenti una matrice idrofoba sono particolarmente stabili e garantiscono un efficace rilascio della glucosammina per 24 ore quando la preparazione della compressa viene effettuata per dispersione della glucosammina nella matrice idrofoba per trattamento ad una temperatura di almeno 70°C. We have now found that controlled release glucosamine tablets containing a hydrophobic matrix are particularly stable and guarantee effective glucosamine release for 24 hours when the tablet preparation is carried out by dispersing the glucosamine into the hydrophobic matrix by treatment at a temperature of at least 70 °. C.
Costituisce pertanto oggetto della presente invenzione una compressa a rilascio controllato contenente un quantitativo efficace di glucosammina, di un suo sale o di un suo derivato disperso in una matrice idrofoba caratterizzata dal fatto che la dispersione dalla glucosammina, di un suo sale o di un suo derivato nella matrice idrofoba à ̈ effettuata per trattamento ad una temperatura di almeno 70°C. Therefore, the object of the present invention is a controlled-release tablet containing an effective quantity of glucosamine, one of its salt or one of its derivatives dispersed in a hydrophobic matrix characterized by the fact that the dispersion of glucosamine, one of its salt or one of its derivatives in the hydrophobic matrix it is carried out by treatment at a temperature of at least 70 ° C.
La glucosammina viene utilizzata come glucosammina base libera, glucosammina cloridrato, glucosammina solfato, glucosammina solfato 2KCl, N-acetil-glucosammina. Preferibilmente viene utilizzata glucosammina solfato 2KCl. Glucosamine is used as free base glucosamine, glucosamine hydrochloride, glucosamine sulfate, glucosamine sulfate 2KCl, N-acetyl-glucosamine. Preferably, glucosamine sulfate 2KCl is used.
La glucosammina può essere eventualmente utilizzata in associazione con altri principi attivi quali acido ascorbico, vitamina A, vitamina E e condroitina. Glucosamine can possibly be used in association with other active ingredients such as ascorbic acid, vitamin A, vitamin E and chondroitin.
La quantità di glucosammina à ̈ generalmente compresa tra il 30% e l’80% in peso rispetto al peso finale della compressa, più preferibilmente tra il 50% e il 70% in peso. The quantity of glucosamine is generally between 30% and 80% by weight with respect to the final weight of the tablet, more preferably between 50% and 70% by weight.
Qualsiasi matrice idrofoba non termolabile può essere utilizzata per le compresse a rilascio controllato secondo la presente invenzione. Any non-thermolabile hydrophobic matrix can be used for the controlled release tablets according to the present invention.
Esempi di tali matrici sono cere, acidi grassi e loro derivati, come ad esempio cera carnauba, cera d’api, acido stearico, magnesio stearato, acido adipico, acido oleico, gliceril palmitostearato e gliceril behenato. Examples of such matrices are waxes, fatty acids and their derivatives, such as for example carnauba wax, beeswax, stearic acid, magnesium stearate, adipic acid, oleic acid, glyceryl palmitostearate and glyceryl behenate.
Vengono preferibilmente utilizzate matrici a base di acidi grassi e loro derivati, ancor più preferibilmente a base di acido stearico e suoi derivati. Particolarmente preferita à ̈ una matrice a base di acido stearico e magnesio stearato. Matrices based on fatty acids and their derivatives are preferably used, even more preferably based on stearic acid and its derivatives. Particularly preferred is a matrix based on stearic acid and magnesium stearate.
L’acido stearico à ̈ preferibilmente utilizzato in una quantità tra il 20% ed il 40% in peso rispetto al peso della compressa più preferibilmente tra il 25% ed il 30% in peso rispetto al peso della compressa. Stearic acid is preferably used in an amount between 20% and 40% by weight with respect to the weight of the tablet, more preferably between 25% and 30% by weight with respect to the weight of the tablet.
Il magnesio stearato à ̈ preferibilmente utilizzato in quantità tra il 2% e l’8% in peso rispetto al peso della compressa, più preferibilmente tra il 4% ed il 6% in peso rispetto al peso della compressa. Magnesium stearate is preferably used in quantities between 2% and 8% by weight with respect to the weight of the tablet, more preferably between 4% and 6% by weight with respect to the weight of the tablet.
La compressa può eventualmente essere rivestita con un film a base di cellulosa o di un altro polimero o miscela di polimeri convenzionalmente utilizzati per la filmatura di compresse. The tablet can optionally be coated with a cellulose-based film or another polymer or mixture of polymers conventionally used for film-forming tablets.
Quando viene filmata, la compressa preparata secondo la presente invenzione à ̈ preferibilmente rivestita con un film a base di cellulosa quale ad esempio Opadry Colorcon. When filmed, the tablet prepared according to the present invention is preferably coated with a cellulose-based film such as for example Opadry Colorcon.
La compressa può contenere, in aggiunta alla matrice idrofoba, anche altri eccipienti normalmente utilizzati nella preparazione di compresse quali diluenti, leganti, disgreganti, glidanti, antiaderenti, aromatizzanti, coloranti, ecc. The tablet may contain, in addition to the hydrophobic matrix, also other excipients normally used in the preparation of tablets such as diluents, binders, disintegrants, glidants, non-stick, flavoring, coloring, etc.
Preferibilmente le compresse secondo la presente invenzione contengono solo la matrice idrofobica ed un eventuale film di rivestimento. Preferably the tablets according to the present invention contain only the hydrophobic matrix and a possible coating film.
La caratteristica delle compresse della presente invenzione à ̈ rappresentata dal processo di preparazione che prevede la dispersione della glucosammina nella matrice idrofoba per trattamento ad una temperatura superiore a 70°C. The characteristic of the tablets of the present invention is represented by the preparation process which provides for the dispersion of glucosamine in the hydrophobic matrix by treatment at a temperature higher than 70 ° C.
Costituisce pertanto un ulteriore oggetto della presente invenzione un processo per la preparazione di compresse a rilascio controllato contenenti glucosammina, un suo sale o un suo derivato ed una matrice idrofoba comprendente la dispersione della glucosammina, del suo sale o del suo derivato nella matrice idrofoba per trattamento ad una temperatura superiore ad 70°C. Therefore, a further object of the present invention is a process for the preparation of controlled-release tablets containing glucosamine, its salt or its derivative and a hydrophobic matrix comprising the dispersion of glucosamine, its salt or its derivative in the hydrophobic matrix for treatment at a temperature above 70 ° C.
La compressa secondo la presente invenzione può quindi essere preparata utilizzando tecniche di fusione, miscelazione o granulazione a secco o ad umido operando a temperature superiori a 70°C. The tablet according to the present invention can therefore be prepared using dry or wet melting, mixing or granulation techniques operating at temperatures above 70 ° C.
Preferibilmente viene utilizzata la fusione in forno della miscela di glucosammina e della matrice idrofoba. The melting of the glucosamine mixture and the hydrophobic matrix is preferably used.
Dopo il trattamento a temperatura superiore a 70°C, la miscela ottenuta viene compressa ed eventualmente rivestita secondo tecniche convenzionali. After the treatment at a temperature higher than 70 ° C, the mixture obtained is compressed and optionally coated according to conventional techniques.
Il limite superiore dell’intervallo di temperatura operativa del processo di preparazione delle compresse secondo la presente invenzione sarà scelto in funzione del tipo di processo utilizzato e della stabilità termica dei componenti della compressa. The upper limit of the operating temperature range of the tablet preparation process according to the present invention will be chosen according to the type of process used and the thermal stability of the tablet components.
E’ evidente che la temperatura non potrà essere superiore a 100°C in caso di utilizzo di processi acquosi mentre potrà essere più elevata in caso di utilizzo di processi a secco. It is evident that the temperature cannot be higher than 100 ° C in case of use of aqueous processes while it could be higher in case of use of dry processes.
Tuttavia per motivi pratici ed economici si preferisce effettuare la dispersione della glucosammina nella matrice idrofoba ad una temperatura tra 70°C e 100°C. However, for practical and economic reasons it is preferred to carry out the dispersion of the glucosamine in the hydrophobic matrix at a temperature between 70 ° C and 100 ° C.
Le compresse preparate secondo la presente invenzione rilasciano efficacemente e costantemente glucosammina per un periodo di circa 12 ore come mostrato in fig.1. The tablets prepared according to the present invention efficiently and constantly release glucosamine for a period of about 12 hours as shown in fig. 1.
Le compresse presentano inoltre un’elevata stabilità . Il loro aspetto rimane inalterato dopo conservazione per due mesi a 40°C e 75% di umidità relativa. The tablets also have a high stability. Their appearance remains unchanged after storage for two months at 40 ° C and 75% relative humidity.
Allo scopo di meglio illustrare la presente invenzione senza tuttavia limitarla vengono ora forniti i seguenti esempi. In order to better illustrate the present invention without however limiting it, the following examples are now provided.
Preparazione di compresse contenenti glucosammina (750 mg), acido stearico (300 mg) e magnesio stearato (50 mg). Preparation of tablets containing glucosamine (750 mg), stearic acid (300 mg) and magnesium stearate (50 mg).
Esempio 1 Example 1
Preparazione per fusione in forno Preparation for melting in the oven
Glucosammina solfato 2KCl, acido stearico e 50% di magnesio stearato sono stati miscelati in un miscelatore a cubo per 10 minuti. La polvere miscelata à ̈ stata caricata in un forno e scaldata a 80°C per circa 2 ore. Il prodotto fuso à ̈ stato raffreddato a temperatura ambiente e quindi setacciato attraverso un granulatore oscillante per ridurre la dimensione particellare dei granuli. Il granulato à ̈ stato miscelato con il restante magnesio stearato in un miscelatore a cubo e compresso in compresse a forma di capsula del peso di 1100 mg. Glucosamine sulfate 2KCl, stearic acid and 50% magnesium stearate were mixed in a cube mixer for 10 minutes. The mixed powder was loaded into an oven and heated to 80 ° C for about 2 hours. The molten product was cooled to room temperature and then sieved through an oscillating granulator to reduce the particle size of the granules. The granules were mixed with the remaining magnesium stearate in a cube blender and compressed into capsule-shaped tablets weighing 1100 mg.
Esempio 2 Example 2
Preparazione per granulazione con acqua Preparation for granulation with water
Glucosammina solfato 2KCl, acido stearico e 50% di magnesio stearato sono stati miscelati in un miscelatore ad alto potere di taglio per 1 minuto. E’ stata aggiunta acqua bollente e miscelata ad alta velocità per 10 minuti. Il granulato à ̈ stato scaricato dal miscelatore ad un granulatore a letto fluido per l’essiccamento. Al granulato à ̈ stato aggiunto il restante magnesio stearato miscelando in un miscelatore a cubo. La miscela risultante à ̈ stata compressa in compresse a forma di capsula del peso di 1100 mg. Glucosamine sulfate 2KCl, stearic acid and 50% magnesium stearate were mixed in a high shear mixer for 1 minute. Boiling water was added and mixed at high speed for 10 minutes. The granulate was discharged from the mixer to a fluidized bed granulator for drying. The remaining magnesium stearate was added to the granulate by mixing in a cube mixer. The resulting mixture was compressed into capsule-shaped tablets weighing 1100 mg.
Esempio 3 Example 3
Preparazione per granulazione a caldo Preparation for hot granulation
Glucosammina solfato 2KCl, acido stearico e 50% di magnesio stearato sono stati miscelati in un rotogranulatore. La miscela à ̈ stata scaldata a 80°C per 15 minuti mantenendo la massima velocità di agitazione. Il prodotto fuso à ̈ stato raffreddato a temperatura ambiente sotto blanda agitazione e quindi setacciato attraverso un granulatore oscillante per ridurre la dimensione particellare dei granuli. Il granulato à ̈ stato miscelato con il restante magnesio stearato in un miscelatore a cubo e compresso in compresse a forma di capsula del peso di 1100 mg. Glucosamine sulfate 2KCl, stearic acid and 50% magnesium stearate were mixed in a rotogranulator. The mixture was heated to 80 ° C for 15 minutes maintaining the maximum stirring speed. The molten product was cooled to room temperature under gentle stirring and then sieved through an oscillating granulator to reduce the particle size of the granules. The granules were mixed with the remaining magnesium stearate in a cube blender and compressed into capsule-shaped tablets weighing 1100 mg.
Esempio 4 Example 4
Preparazione per granulazione con acqua Preparation for granulation with water
Glucosammina solfato 2KCl, acido stearico e 50% di magnesio stearato sono stati miscelati in un rotogranulatore. La miscela à ̈ stata scaldata a 80°C per 15 minuti mantenendo la massima velocità di agitazione ed à ̈’ stata quindi aggiunta acqua bollente sempre mantenendo la massima velocità di agitazione. La miscela à ̈ stata essiccata sotto vuoto per circa 1 ora. Il prodotto fuso à ̈ stato raffreddato a temperatura ambiente ed il granulato à ̈ stato setacciato attraverso un granulatore oscillante per ridurre la dimensione particellare dei granuli. Il granulato à ̈ stato miscelato con il restante magnesio stearato in un miscelatore a cubo e compresso in compresse a forma di capsula del peso di 1100 mg. Glucosamine sulfate 2KCl, stearic acid and 50% magnesium stearate were mixed in a rotogranulator. The mixture was heated to 80 ° C for 15 minutes maintaining the maximum stirring speed and boiling water was then added while maintaining the maximum stirring speed. The mixture was dried under vacuum for about 1 hour. The molten product was cooled to room temperature and the granulate was sieved through an oscillating granulator to reduce the particle size of the granules. The granules were mixed with the remaining magnesium stearate in a cube blender and compressed into capsule-shaped tablets weighing 1100 mg.
Preparazione di compresse contenenti glucosammina (750 mg), acido stearico (300 mg). magnesio stearato (50 mg) ed acido ascorbico (12 mg). Preparation of tablets containing glucosamine (750 mg), stearic acid (300 mg). magnesium stearate (50 mg) and ascorbic acid (12 mg).
Esempio 5 Example 5
Preparazione per fusione in forno Preparation for melting in the oven
Glucosammina solfato 2KCl, acido stearico, acido ascorbico e 50% di magnesio stearato sono stati miscelati in un miscelatore a cubo per 10 minuti. La polvere miscelata à ̈ stata caricata in un forno e scaldata a 80°C per circa 2 ore. Il prodotto fuso à ̈ stato raffreddato a temperatura ambiente e quindi setacciato attraverso un granulatore oscillante per ridurre la dimensione particellare dei granuli. Il granulato à ̈ stato miscelato con il restante magnesio stearato in un miscelatore a cubo e compresso in compresse a forma di capsula del peso di 1112 mg. Glucosamine sulfate 2KCl, stearic acid, ascorbic acid and 50% magnesium stearate were mixed in a cube blender for 10 minutes. The mixed powder was loaded into an oven and heated to 80 ° C for about 2 hours. The molten product was cooled to room temperature and then sieved through an oscillating granulator to reduce the particle size of the granules. The granules were mixed with the remaining magnesium stearate in a cube blender and compressed into capsule-shaped tablets weighing 1112 mg.
Claims (4)
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ITMI2010A001102A IT1400578B1 (en) | 2010-06-18 | 2010-06-18 | PROCESS FOR THE PREPARATION OF TABLETS WITH CONTROLLED RELEASE. |
| PCT/EP2011/059886 WO2011157730A1 (en) | 2010-06-18 | 2011-06-15 | Process for the preparation of controlled release tablet |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ITMI2010A001102A IT1400578B1 (en) | 2010-06-18 | 2010-06-18 | PROCESS FOR THE PREPARATION OF TABLETS WITH CONTROLLED RELEASE. |
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| ITMI20101102A1 true ITMI20101102A1 (en) | 2011-12-19 |
| IT1400578B1 IT1400578B1 (en) | 2013-06-14 |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040234599A1 (en) * | 2000-08-29 | 2004-11-25 | Leiner Health Services Corp. | Composition and method for maintaining healthy mobile joints and cartilage |
| WO2008136016A1 (en) * | 2007-05-08 | 2008-11-13 | Medreich Limited | A stable controlled release oral solid dosage form composition and a process thereof |
| US20100010101A1 (en) * | 2000-07-05 | 2010-01-14 | Capricorn Pharma, Inc. | Rapid-Melt Compositions and Methods of Making Same |
| WO2010028290A1 (en) * | 2008-09-04 | 2010-03-11 | Farnam Companies, Inc. | Chewable sustained release formulations |
-
2010
- 2010-06-18 IT ITMI2010A001102A patent/IT1400578B1/en active
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- 2011-06-15 WO PCT/EP2011/059886 patent/WO2011157730A1/en active Application Filing
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20100010101A1 (en) * | 2000-07-05 | 2010-01-14 | Capricorn Pharma, Inc. | Rapid-Melt Compositions and Methods of Making Same |
| US20040234599A1 (en) * | 2000-08-29 | 2004-11-25 | Leiner Health Services Corp. | Composition and method for maintaining healthy mobile joints and cartilage |
| WO2008136016A1 (en) * | 2007-05-08 | 2008-11-13 | Medreich Limited | A stable controlled release oral solid dosage form composition and a process thereof |
| WO2010028290A1 (en) * | 2008-09-04 | 2010-03-11 | Farnam Companies, Inc. | Chewable sustained release formulations |
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| IT1400578B1 (en) | 2013-06-14 |
| WO2011157730A1 (en) | 2011-12-22 |
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