ITMI20001868A1 - PHARMACEUTICAL COMPOSITION CONTAINING LITHIUM CARBONATE. - Google Patents
PHARMACEUTICAL COMPOSITION CONTAINING LITHIUM CARBONATE. Download PDFInfo
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- ITMI20001868A1 ITMI20001868A1 IT2000MI001868A ITMI20001868A ITMI20001868A1 IT MI20001868 A1 ITMI20001868 A1 IT MI20001868A1 IT 2000MI001868 A IT2000MI001868 A IT 2000MI001868A IT MI20001868 A ITMI20001868 A IT MI20001868A IT MI20001868 A1 ITMI20001868 A1 IT MI20001868A1
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- Prior art keywords
- lithium carbonate
- granules
- pharmaceutical composition
- composition containing
- containing lithium
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- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 title claims description 21
- 229910052808 lithium carbonate Inorganic materials 0.000 title claims description 19
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 3
- 239000008187 granular material Substances 0.000 claims description 22
- 239000000203 mixture Substances 0.000 claims description 7
- 239000001856 Ethyl cellulose Substances 0.000 claims description 5
- 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 claims description 5
- 229920001249 ethyl cellulose Polymers 0.000 claims description 5
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 5
- 239000007903 gelatin capsule Substances 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 4
- 239000000454 talc Substances 0.000 claims description 4
- 229910052623 talc Inorganic materials 0.000 claims description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims 2
- 238000002360 preparation method Methods 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- 239000011248 coating agent Substances 0.000 description 6
- 238000000576 coating method Methods 0.000 description 5
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 229910052744 lithium Inorganic materials 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
- 238000000034 method Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 239000011230 binding agent Substances 0.000 description 3
- 238000005538 encapsulation Methods 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 238000005507 spraying Methods 0.000 description 3
- 229910001220 stainless steel Inorganic materials 0.000 description 3
- 239000010935 stainless steel Substances 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000004931 aggregating effect Effects 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000007931 coated granule Substances 0.000 description 2
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
- 239000011928 denatured alcohol Substances 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 229940069328 povidone Drugs 0.000 description 2
- 230000007928 solubilization Effects 0.000 description 2
- 238000005063 solubilization Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 206010026749 Mania Diseases 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 208000028017 Psychotic disease Diseases 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
- 238000013459 approach Methods 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229940109239 creatinine Drugs 0.000 description 1
- 230000003001 depressive effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000007922 dissolution test Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- KHLVKKOJDHCJMG-QDBORUFSSA-L indigo carmine Chemical compound [Na+].[Na+].N/1C2=CC=C(S([O-])(=O)=O)C=C2C(=O)C\1=C1/NC2=CC=C(S(=O)(=O)[O-])C=C2C1=O KHLVKKOJDHCJMG-QDBORUFSSA-L 0.000 description 1
- 229960003988 indigo carmine Drugs 0.000 description 1
- 235000012738 indigotine Nutrition 0.000 description 1
- 239000004179 indigotine Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229910003002 lithium salt Inorganic materials 0.000 description 1
- 159000000002 lithium salts Chemical class 0.000 description 1
- 238000009136 lithium therapy Methods 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- -1 polyethylene Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 235000010215 titanium dioxide Nutrition 0.000 description 1
- 231100000816 toxic dose Toxicity 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 210000005239 tubule Anatomy 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Description
Descrizione del brevetto per invenzione industriale avente per titolo: Description of the patent for industrial invention entitled:
“COMPOSIZIONE FARMACEUTICA CONTENENTE LITIO CARBONATO' "PHARMACEUTICAL COMPOSITION CONTAINING LITHIUM CARBONATE"
La presente invenzione si riferisce a una formulazione di litio carbonato a lento rilascio. The present invention relates to a slow-release lithium carbonate formulation.
L’impiego di sali di litio nel trattamento degli stati depressivi e maniacali, delle psicosi e di certe forme di cefalea, è noto da diversi anni. Uno dei maggiori problemi legati alla terapia con litio è rappresentato dal suo basso indice terapeutico da un Iato, e dalla necessità di garantire il mantenimento di concentrazioni costanti terapeuticamente utili, al di sotto dei limiti di tossicità, dall’altro. Un adeguato regime terapeutico può essere ottenuto con le attuali preparazioni in commercio ricorrendo a due o tre somministrazioni giornaliere. Il litio carbonato è completamente assorbito a livello gastro-intestinale in circa 8 ore con un picco di concentrazione piasmatica tra le 2 e le 4 ore. Dopo essere stato assorbito, il catione si distribuisce lentamente dentro le cellule di diversi organi e il suo volume di distribuzione si avvicina all’unità (0,7-0, 9), raggiungendo allo “steady-state” una concentrazione nel liquor inferiore del 50% rispetto a quella piasmatica. Alla prima somministrazione l’emivita iniziale è abbreviata dalla ridistribuzione. Allo “steady-state” l’emivita piasmatica è di 20-24 ore. Il litio viene eliminato con le urine per oltre il 95%; come il sodio viene riassorbito per l’80% nel tubulo contorto prossimale ed ha una clearance corrispondente a circa il 20% di quella della creatinina. Minori sono i picchi di concentrazione di litio raggiunti nel plasma, più costante sarà la sua eliminazione. E’ quindi desiderabile disporre di un preparato a lento rilascio che riduca il numero di somministrazioni giornaliere e il valore dei picchi plasmatici, evitando cosi il raggiungimento di concentrazioni tossiche e aumentando la compliance del paziente. The use of lithium salts in the treatment of depressive and manic states, psychosis and certain forms of headache has been known for several years. One of the major problems associated with lithium therapy is its low therapeutic index on one side, and the need to ensure the maintenance of therapeutically useful constant concentrations, below the toxicity limits, on the other. An adequate therapeutic regimen can be obtained with the current preparations on the market by resorting to two or three daily administrations. Lithium carbonate is completely absorbed in the gastrointestinal tract in about 8 hours with a peak piasmatic concentration between 2 and 4 hours. After being absorbed, the cation is distributed slowly into the cells of different organs and its volume of distribution approaches unity (0.7-0.9), reaching a "steady-state" concentration in the lower liquor of the 50% compared to the piasmatic one. At the first administration, the initial half-life is shortened by redistribution. At the "steady-state" the piasmatic half-life is 20-24 hours. More than 95% of lithium is eliminated in the urine; how sodium is reabsorbed for 80% in the proximal convoluted tubule and has a clearance corresponding to about 20% of that of creatinine. The lower the peaks of lithium concentration reached in the plasma, the more constant its elimination will be. It is therefore desirable to have a slow-release preparation that reduces the number of daily administrations and the value of plasma peaks, thus avoiding the achievement of toxic concentrations and increasing patient compliance.
Oggetto della presente domanda di brevetto è una formulazione di litio carbonato a rilascio protratto che soddisfa i requisiti farmacocinetici sopra indicati, garantendo una concentrazione piasmatica costante nelle 24 ore a livelli compatibili con i margini di sicurezza stabiliti. La composizione dell’ invenzione è in forma di granulato rivestito ed ha il seguente contenuto, espresso in % in peso: litio carbonato 93%, etilcellulosa 1,7%, talco 0,8%, polivinilpirrolidone 4,5%. Il rivestimento dei granuli può essere condotto con tecniche note, preferibilmente con la tecnica in letto fluido spruzzando sui granuli di principio attivo una soluzione dell’agente di rivestimento (etilcellulosa) in alcool, acetone e acqua. I granuli rivestiti vengono quindi incorporati in un opportuno veicolo per somministrazione orale. Capsule di gelatina dura rappresentano la forma di somministrazione d’elezione. Le capsule vengono preparate secondo tecniche convenzionali, per esempio come descritto in Remington’s Pharmaceutical Sciences Handbook, Mack Pub. Co., NY, USA, XVII Ed. In aggiunta alla gelatina e agli eventuali coloranti, le capsule possono contenere sodio laurilsolfato e magnesio stearato rispettivamente come agente di dissoluzione e diluente. The subject of the present patent application is a prolonged-release lithium carbonate formulation that satisfies the pharmacokinetic requirements indicated above, guaranteeing a constant piasmatic concentration over 24 hours at levels compatible with the established safety margins. The composition of the invention is in the form of coated granules and has the following content, expressed in% by weight: 93% lithium carbonate, 1.7% ethylcellulose, 0.8% talc, 4.5% polyvinylpyrrolidone. The coating of the granules can be carried out with known techniques, preferably with the fluid bed technique by spraying on the granules of the active ingredient a solution of the coating agent (ethylcellulose) in alcohol, acetone and water. The coated granules are then incorporated into a suitable vehicle for oral administration. Hard gelatin capsules represent the preferred form of administration. The capsules are prepared according to conventional techniques, for example as described in Remington's Pharmaceutical Sciences Handbook, Mack Pub. Co., NY, USA, 17th Ed. In addition to gelatin and any dyes, the capsules may contain sodium lauryl sulfate and magnesium stearate as dissolving and diluting agents, respectively.
I granuli rivestiti e incorporati in un opportuno veicolo, preferibilmente in capsule di gelatina dura, garantiscono un rilascio del principio attivo costante nell’arco delle 24 ore, senza dare i picchi ematici di assorbimento che si osservano comunemente dopo somministrazione di litio. In un tipico test di dissoluzione condotto con sei campioni di formulazione utilizzando una soluzione a pH 1,1 in dissolutore a flusso continuo (25 ml/min, 37°C), si sono ottenute le seguenti percentuali di rilascio durante le 24 ore: The granules coated and incorporated in a suitable vehicle, preferably in hard gelatin capsules, ensure a constant release of the active ingredient over 24 hours, without giving the blood absorption peaks that are commonly observed after lithium administration. In a typical dissolution test conducted with six formulation samples using a solution at pH 1.1 in a continuous flow dissolver (25 ml / min, 37 ° C), the following release rates were obtained during the 24 hours:
Tabella Table
Dai dati riportati in tabella si evince chiaramente la costanza di rilascio del principio attivo nell’ intero periodo esaminato. The data shown in the table clearly shows the constant release of the active ingredient over the entire period examined.
Sono inoltre stati condotti studi di bioequivalenza rispetto ad una composizione in commercio (CARBOLITHIUM®) contenente granuli di litio carbonato in microcapsule composte da magnesio stearato, gelatina, titanio biossido, indigotina, lattosio, amido, metilcellulosa. I risultati sono riportati in Figura. Dal grafico in Figura si osserva chiaramente che la concentrazione piasmatica di litio si mantiene costante nel periodo di 24 ore dopo somministrazione della composizione dell’invenzione, mentre con il prodotto di confronto si notano i tipici picchi di assorbimento che potrebbero comportare rischi per il paziente trattato. Bioequivalence studies were also conducted with respect to a composition on the market (CARBOLITHIUM®) containing lithium carbonate granules in microcapsules composed of magnesium stearate, gelatin, titanium dioxide, indigo carmine, lactose, starch, methylcellulose. The results are shown in Figure. From the graph in the Figure it is clearly observed that the piasmatic concentration of lithium remains constant in the period of 24 hours after administration of the composition of the invention, while with the comparative product the typical absorption peaks are noted which could involve risks for the treated patient. .
La farmacocinetica particolarmente favorevole consente la somministrazione di un’unica dose giornaliera, aumentando di molto la compliance del paziente. I dosaggi previsti per il principio attivo possono variare da un minimo di 300mg ad un massimo di 900mg, e dipenderanno da fattori quali la gravità del disturbo da trattare, l’età, il peso e lo stato di salute del paziente. Generalmente, un dosaggio di 600 nig di litio carbonato in un’unica dose giornaliera garantisce risultati ottimali. The particularly favorable pharmacokinetics allows the administration of a single daily dose, greatly increasing patient compliance. The dosages provided for the active ingredient can vary from a minimum of 300mg to a maximum of 900mg, and will depend on factors such as the severity of the disorder to be treated, the age, weight and state of health of the patient. Generally, a dosage of 600 nig of lithium carbonate in a single daily dose guarantees optimal results.
L’esempio che segue illustra la preparazione di litio carbonato 600mg. ESEMPIO - preparazione di 250.000 dosi/capsule The following example illustrates the preparation of 600mg lithium carbonate. EXAMPLE - preparation of 250,000 doses / capsules
Formula di fabbricazione Manufacturing formula
Quantitativi standard per la fabbricazione di 250.000 capsule di Litio Carbonato da 600 mg a lento rilascio: Standard quantities for the manufacture of 250,000 slow-release 600 mg lithium carbonate capsules:
Litio Carbonato 150 Kg Povidone 7,300 Kg Etilcellulosa 2,575 Kg Talco 1,125 Kg Acetone* q.b. Lithium Carbonate 150 Kg Povidone 7,300 Kg Ethylcellulose 2,575 Kg Talc 1,125 Kg Acetone * q.s.
Alcool denaturato* q.b. Denatured alcohol * to taste
Acqua* q.b. Water * to taste
* solventi utilizzati nel processo di fabbricazione. * solvents used in the manufacturing process.
Preparazione della soluzione legante Preparation of the binder solution
Viene immessa acqua in un contenitore di acciaio inox equipaggiato con un agitatore pneumatico e quindi viene versato a pioggia, a piccole quantità, il Povidone. L’agitazione viene protratta fino ad avvenuta solubilazzazione. Water is introduced into a stainless steel container equipped with a pneumatic agitator and then the Povidone is poured in small quantities. The stirring is continued until solubilization has taken place.
Preparazione dei granuli di litio carbonato non rivestiti Preparation of uncoated lithium carbonate granules
Viene accuratamente pesata una parte di litio carbonato e granulata nel granulatore usando come aggregante la soluzione legante sopra descritta. A part of lithium carbonate is carefully weighed and granulated in the granulator using the binder solution described above as aggregating agent.
Il granulato umido viene forzato attraverso una rete con maglie di 840 micron, essiccato a 40°C per 15 ore in un essiccatore termostatato a circolazione d’aria forzata e successivamente il granulato viene setacciato con un setaccio con maglie di 500 e 840 micron. The wet granulate is forced through a mesh with 840 micron mesh, dried at 40 ° C for 15 hours in a forced air circulation thermostatted dryer and then the granulate is sieved with a sieve with 500 and 840 micron mesh.
La polvere ed i granuli più piccoli di 500 micron vengono rigranulati con la medesima procedura descritta precedentemente, ma usando come aggregante acqua. Alla fine del procedimento di granulazione i granuli vengono setacciati con un setaccio con maglie di 500 e 840 micron. The powder and granules smaller than 500 microns are re-granulated with the same procedure described above, but using water as an aggregating agent. At the end of the granulation process, the granules are sieved with a sieve with meshes of 500 and 840 microns.
Il granulato ottenuto viene pesato e messo nel cestello di acciaio inox della bassina. Mentre la bassina gira a una velocità idonea ad assicurare una buona rotazione della massa (circa 12 rpm), la soluzione legante viene spruzzata sui granuli mediante un dispositivo a spruzzo e viene addizionata polvere di litio carbonato. The granulate obtained is weighed and placed in the stainless steel basket of the pan. While the pan rotates at a speed suitable to ensure a good rotation of the mass (about 12 rpm), the binder solution is sprayed onto the granules by means of a spray device and lithium carbonate powder is added.
La spruzzatura viene fatta ad intervalli al fine di consentire una migliore evaporazione del solvente, rimosso mediante un sistema di aspirazione, ed evitare possibili bolle. The spraying is done at intervals in order to allow a better evaporation of the solvent, removed by a suction system, and to avoid possible bubbles.
Alla fine il granulato viene setacciato con una rete con maglia di 1200 micron ed essiccato a 40°C per 15 ore in un essiccatore termostatato con aria a circolazione forzata. At the end the granulate is sieved with a 1200 micron mesh and dried at 40 ° C for 15 hours in a thermostated dryer with forced circulation air.
Il granulato viene nuovamente setacciato con un setaccio con maglie di 840 e 1200 micron. The granulate is sieved again with a sieve with meshes of 840 and 1200 microns.
Preparazione del film di rivestimento in soluzione Preparation of the solution coating film
Acetone ed alcool denaturato vengono messi nel serbatoio di acciaio inox e, sotto continua agitazione, viene addizionata l’etilcellulosa. Acetone and denatured alcohol are placed in the stainless steel tank and, under continuous stirring, ethyl cellulose is added.
Si agita fino a completa solubilizzazione. It is stirred until complete solubilization.
Rivestimento dei granuli di litio carbonato Coating of lithium carbonate granules
I granuli di litio carbonato vengono messi all’ interno di un letto fluido e spruzzati con il film di rivestimento. The lithium carbonate granules are placed inside a fluid bed and sprayed with the coating film.
Inoltre alla fine di ciascun intervallo di spruzzatura vengono buttate sul granulato piccole quantità di talco per migliorare lo scorrimento della massa. Furthermore, at the end of each spraying interval, small quantities of talc are thrown onto the granulate to improve the flow of the mass.
Alla fine dell’operazione, i granuli vengono forzati attraverso una rete con maglie di 1200 micron. At the end of the operation, the granules are forced through a 1200 micron mesh.
Finito il ciclo di rivestimento, il granulato viene essiccato. At the end of the coating cycle, the granulate is dried.
Da ultimo il granulato viene setacciato con un setaccio con maglie di 840 e 1340 micron. Finally, the granulate is sieved with a sieve with meshes of 840 and 1340 microns.
Incapsulazione Encapsulation
Per incapsulazione si intende la ripartita del granulato di litio carbonato in capsule di gelatina dura. By encapsulation we mean the breakdown of the lithium carbonate granules into hard gelatin capsules.
L' incapsulazione è effettuata mediante una macchina automatica (opercolatrice) programmata a riempire capsule di gelatina dura con il peso previsto di granulato (mg). The encapsulation is carried out by means of an automatic machine (capsule filling machine) programmed to fill hard gelatin capsules with the expected weight of granules (mg).
Le capsule riempite e chiuse vengono raccolte sotto controllo visivo continuo in una doppia sacca di polietilene inserita in un fustino di metallo con The filled and closed capsules are collected under continuous visual control in a double polyethylene bag inserted in a metal drum with
Claims (3)
Priority Applications (15)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ITMI20001868 ITMI20001868T1 (en) | 2000-08-10 | 2000-08-10 | Pharmaceutical composition containing lithium carbonate |
| IT2000MI001868A IT1318677B1 (en) | 2000-08-10 | 2000-08-10 | Pharmaceutical composition useful in the treatment of depressive and manic disorders comprises lithium carbonate, ethyl cellulose, talc and polyvinylpyrrolidone |
| CNB018139760A CN1230150C (en) | 2000-08-10 | 2001-08-06 | 'low release' pharmaceutical compositions comprising lithium carbonate |
| US10/343,997 US6989159B2 (en) | 2000-08-10 | 2001-08-06 | Pharmaceutical compositions containing lithium carbonate |
| DE60110814T DE60110814D1 (en) | 2000-08-10 | 2001-08-06 | COMPOSITIONS WITH SLOW RELEASE CONTAINING LITHIUM CARBONATE |
| EA200300128A EA200300128A1 (en) | 2000-08-10 | 2001-08-06 | PHARMACEUTICAL COMPOSITIONS CONTAINING LITHIUM CARBONATE |
| BR0113070-6A BR0113070A (en) | 2000-08-10 | 2001-08-06 | Lithium carbonate containing pharmaceutical compositions |
| AT01971873T ATE295154T1 (en) | 2000-08-10 | 2001-08-06 | SLOW RELEASE COMPOSITIONS CONTAINING LITHIUM CARBONATE |
| PCT/EP2001/009054 WO2002011740A2 (en) | 2000-08-10 | 2001-08-06 | 'slow release' pharmaceutical compositions comprising lithium carbonate |
| JP2002517075A JP2004505923A (en) | 2000-08-10 | 2001-08-06 | "Sustained-release" pharmaceutical composition containing lithium carbonate |
| AU2001291738A AU2001291738A1 (en) | 2000-08-10 | 2001-08-06 | "Slow release" pharmaceutical compositions comprising lithium carbonate |
| EP01971873A EP1315480B1 (en) | 2000-08-10 | 2001-08-06 | "slow release" pharmaceutical compositions comprising lithium carbonate |
| CA002417930A CA2417930A1 (en) | 2000-08-10 | 2001-08-06 | Pharmaceutical compositions containing lithium carbonate |
| US11/122,742 US20050208154A1 (en) | 2000-08-10 | 2005-05-05 | Pharmaceutical compositions containing lithium carbonate |
| US11/978,703 US20080124390A1 (en) | 2000-08-10 | 2007-10-29 | Pharmaceutical compositions containing lithium carbonate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT2000MI001868A IT1318677B1 (en) | 2000-08-10 | 2000-08-10 | Pharmaceutical composition useful in the treatment of depressive and manic disorders comprises lithium carbonate, ethyl cellulose, talc and polyvinylpyrrolidone |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| ITMI20001868A0 ITMI20001868A0 (en) | 2000-08-10 |
| ITMI20001868A1 true ITMI20001868A1 (en) | 2002-02-10 |
| IT1318677B1 IT1318677B1 (en) | 2003-08-27 |
Family
ID=11445704
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IT2000MI001868A IT1318677B1 (en) | 2000-08-10 | 2000-08-10 | Pharmaceutical composition useful in the treatment of depressive and manic disorders comprises lithium carbonate, ethyl cellulose, talc and polyvinylpyrrolidone |
| ITMI20001868 ITMI20001868T1 (en) | 2000-08-10 | 2000-08-10 | Pharmaceutical composition containing lithium carbonate |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ITMI20001868 ITMI20001868T1 (en) | 2000-08-10 | 2000-08-10 | Pharmaceutical composition containing lithium carbonate |
Country Status (1)
| Country | Link |
|---|---|
| IT (2) | IT1318677B1 (en) |
-
2000
- 2000-08-10 IT IT2000MI001868A patent/IT1318677B1/en active
- 2000-08-10 IT ITMI20001868 patent/ITMI20001868T1/en active
Also Published As
| Publication number | Publication date |
|---|---|
| ITMI20001868T1 (en) | 2002-02-11 |
| IT1318677B1 (en) | 2003-08-27 |
| ITMI20001868A0 (en) | 2000-08-10 |
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