SK16642001A3 - Pharmaceutical formulation in granular form - Google Patents
Pharmaceutical formulation in granular form Download PDFInfo
- Publication number
- SK16642001A3 SK16642001A3 SK1664-2001A SK16642001A SK16642001A3 SK 16642001 A3 SK16642001 A3 SK 16642001A3 SK 16642001 A SK16642001 A SK 16642001A SK 16642001 A3 SK16642001 A3 SK 16642001A3
- Authority
- SK
- Slovakia
- Prior art keywords
- pharmaceutical compound
- compound according
- clarithromycin
- granulate
- pharmaceutically acceptable
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title description 3
- 239000011248 coating agent Substances 0.000 claims abstract description 13
- 238000000576 coating method Methods 0.000 claims abstract description 13
- 238000000034 method Methods 0.000 claims abstract description 11
- 150000001875 compounds Chemical class 0.000 claims description 31
- 229960002626 clarithromycin Drugs 0.000 claims description 29
- AGOYDEPGAOXOCK-KCBOHYOISA-N clarithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@](C)([C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)OC)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 AGOYDEPGAOXOCK-KCBOHYOISA-N 0.000 claims description 28
- 239000008187 granular material Substances 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 15
- 239000000725 suspension Substances 0.000 claims description 11
- 239000000654 additive Substances 0.000 claims description 8
- 238000002844 melting Methods 0.000 claims description 8
- 230000008018 melting Effects 0.000 claims description 8
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- 239000000203 mixture Substances 0.000 claims description 6
- 238000005469 granulation Methods 0.000 claims description 5
- 230000003179 granulation Effects 0.000 claims description 5
- 150000002632 lipids Chemical class 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
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- 239000000126 substance Substances 0.000 claims 5
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- 239000003814 drug Substances 0.000 description 8
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- 239000007864 aqueous solution Substances 0.000 description 2
- NEDGUIRITORSKL-UHFFFAOYSA-N butyl 2-methylprop-2-enoate;2-(dimethylamino)ethyl 2-methylprop-2-enoate;methyl 2-methylprop-2-enoate Chemical compound COC(=O)C(C)=C.CCCCOC(=O)C(C)=C.CN(C)CCOC(=O)C(C)=C NEDGUIRITORSKL-UHFFFAOYSA-N 0.000 description 2
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- 229920003169 water-soluble polymer Polymers 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
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Abstract
Description
Súčasný vynález patrí do oblasti farmaceutickej technológie a objasňuje farmaceutický prostriedok vo forme granulátu. Presnejšie, súčasný vynález objasňuje jednoduchý jednofázový proces poťahovania claritromycínu alebo jeho derivátov pomocou farmaceutického prostriedku vo forme granulátu, aby sme účinne zakryli ich horkú chuť, a tiež vyrobili novú, pre pacienta prijateľnejšiu orálne podávanú farmaceutickú zlúčeninu vhodnú aj pre diabetikov a ktorá zároveň umožní zmeny v množstve a mieste uvolňovania aktívnej zložky.The present invention belongs to the field of pharmaceutical technology and discloses a pharmaceutical composition in the form of a granulate. More specifically, the present invention elucidates a simple single-phase process for coating clarithromycin or derivatives thereof with a pharmaceutical composition in the form of a granulate to effectively mask their bitter taste, and also to produce a new, more patient-friendly orally administrable pharmaceutical compound suitable for diabetics. the amount and site of release of the active ingredient.
Doterajší stav technikyBACKGROUND OF THE INVENTION
Claromycín je základné, vo vode prakticky nerozpustné makrolidné antibiotikum veľmi horkej chuti, ktorá zostáva v ústach aj niekoľko hodín po užití terapeutickej dávky. Pretože niektoré skupiny pacientov (deti, starší ľudia, pacienti s problémami pri prehítani) nemôžu užívať tuhé medicínske preparáty (tabletky, kapsuly) a tie isté skupiny sú veľmi citlivé na (ne)prijateľnú chuť lekárskeho prípravku, vznikla potreba získať efektívne technologické riešenie na prekrytie alebo zmiernenie horkej chuti claritromycínu alebo jeho derivátov, t.j. pripraviť suspenziu na orálne použitie, ktorá by bola pre pacienta prijateľná a terapeuticky účinná.Claromycin is a basic, practically water-insoluble macrolide antibiotic of very bitter taste, which remains in the mouth for several hours after taking a therapeutic dose. Since some patient groups (children, elderly, patients with swallowing problems) cannot take solid medical preparations (tablets, capsules) and the same groups are very sensitive to the (un) acceptable taste of the medicine, there is a need to obtain an effective technological solution to overlap or relieving the bitter taste of clarithromycin or derivatives thereof, i to provide a suspension for oral use that is acceptable and therapeutically effective to the patient.
Komerčne dostupná orálna suspenzia s claritromycínom obsahuje značné množstvo cukru (ktorý ale neeliminuje horkú chuť), a stále má relatívne nepríjemnú chuť, navyše technológia jej prípravy je multifázová, a teda drahá. Teda, súčasný vynález vzišiel z potreby pripraviť orálnu suspenziu s claritromycínom alebo jeho derivátmi, ktorá bude chutná, účinná a bude sa dať získať pri jednofázovom procese. Claritromycín je polosyntetické antibiotikum získané metyláciou erytromycínu v laktónovej pozícii C6. Syntéza je opísaná v US 4,331,803 a US 4,672,109. Je aktívny voči gram-pozitívnym baktériám a vzhľadom na široké spektrum antimikrobiálnej aktivity sa využíva klinicky. Na trhu je dostupný vo forme poťahovaných tabletiek, suspenzií a tabletiek s predĺženým účinkom.The commercially available oral suspension with clarithromycin contains a considerable amount of sugar (but which does not eliminate the bitter taste) and still has a relatively unpleasant taste, moreover, its preparation technology is multi-phase and thus expensive. Thus, the present invention arises from the need to provide an oral suspension with clarithromycin or derivatives thereof that is palatable, effective and obtainable in a single-phase process. Clarithromycin is a semi-synthetic antibiotic obtained by methylation of erythromycin at the lactone position C6. The synthesis is described in US 4,331,803 and US 4,672,109. It is active against gram-positive bacteria and is used clinically due to the broad spectrum of antimicrobial activity. It is available on the market in the form of coated tablets, suspensions and prolonged-release tablets.
Odlišné orálne farmaceutické zlúčeniny s claritromycínom sú opísané v týchto patentoch:Different oral pharmaceutical compounds with clarithromycin are described in the following patents:
JP 85/163823 opisuje orálne liečivo s claritromycínom, kyselinu citrónovú zvyšujúcu vstrebávanie antibiotika v tráviacom trakte, disintegranty, excipienty a lubrikanty.JP 85/163823 discloses an oral drug with clarithromycin, citric acid enhancing the absorption of antibiotics in the digestive tract, disintegrants, excipients and lubricants.
EP 0277042 opisuje orálnu farmaceutickú zlúčeninu (aj s makrolidmi) s vylepšenou chuťou, s vrstvou určitých polymérov, (najmä polyvinyl acetal dithylaminoacetát AEA) rozpustných v žalúdočnej šťave a s priemerom častice pod 60 pm.EP 0277042 describes an oral taste-enhanced oral pharmaceutical compound (including macrolides) with a layer of certain polymers (especially polyvinyl acetal dithylaminoacetate AEA) soluble in gastric juice and having a particle diameter below 60 µm.
US 4,808,411 opisuje farmaceutickú zlúčeninu s erytromicínom alebo jeho derivátmi a karbomérom, podľa možnosti vo forme komplexných iónových častíc obalených polymérom, ktorý môže byť rozptýlený v tekutom nosiči.US 4,808,411 discloses a pharmaceutical compound with erythromicin or derivatives thereof and a carbomer, preferably in the form of complex ionic particles coated with a polymer that can be dispersed in a liquid carrier.
JP 01-308,223 opisuje prípravu filmom potiahnutých mikrogranúl liečiva s dlhodobým účinkom, ktorý obsahuje AEA a vodu ako prídavok ku claritromycínu.JP 01-308,223 describes the preparation of long-acting film-coated drug microgranules containing AEA and water in addition to clarithromycin.
EP 0302370 a WO 90/08537 opisujú vylepšené orálne farmaceutické zlúčeniny (olejový roztok, suspenzia, emulzia) eiytromicýnu a derivátov,ktorými sa plnia mäkké želatínové kapsuly s N-metyl-pyrolidínom.EP 0302370 and WO 90/08537 disclose improved oral pharmaceutical compounds (oily solution, suspension, emulsion) of ithytromycin and derivatives which fill soft gelatin capsules with N-methylpyrrolidine.
EP-B-0420992 opisuje proces výroby orálnej farmaceutickej zlúčeniny (aj s makrolidmi) so zastretou chuťou, pri ktorom sa medikamentózna suspenzia vstrekuje do studeného vodného roztoku AEA.EP-B-0420992 discloses a process for the production of a taste-masked oral pharmaceutical compound (including macrolides) in which a medicament suspension is injected into a cold aqueous solution of AEA.
US 5,017,383 opisuje metódu výroby jemne potiahnutej farmaceutickej zlúčeniny, ktorá pozostáva zo zmiešania zamrznutých častíc tekutého média s liečivom (aj s makrolidmi) a poťahu vo forme jemného prášku, ktorý priľne na povrch častíc.US 5,017,383 discloses a method of manufacturing a finely coated pharmaceutical compound which comprises mixing frozen particles of a liquid medium with a drug (including macrolides) and a coating in the form of a fine powder that adheres to the surface of the particles.
JP 05-255,075 opisuje topnú granuláciu makrolidov, v ktorej poťah pozostáva z polymérov rozpustných v žalúdku (najmä Eudragit E), ktoré sú disperzované v zhlukoch s nízkym bodom topenia. Finálna granulácia sa prevádza striekaním. Konečná príprava suchého sirupu sa končí zmiešaním granúl s cukrom a hydroxypropylmetylcelulózy (HPMC).JP 05-255,075 discloses a heating granulation of macrolides in which the coating consists of stomach-soluble polymers (especially Eudragit E), which are dispersed in low melting point agglomerates. The final granulation is carried out by spraying. The final preparation of the dry syrup is completed by mixing the granules with sugar and hydroxypropyl methylcellulose (HPMC).
US 5.599,556 a US 5,609,909 opisuje maskovanie chuti kapsulovaných claritromycínových častíc s prolamínovaným poťahom pred prípravou suspenzie.US 5,599,556 and US 5,609,909 disclose taste masking of encapsulated clarithromycin particles with a prolaminated coating prior to slurry preparation.
WO 96/34628 opisuje orálnu farmaceutickú zlúčeninu (aj s makrolidmi) na zamaskovanie chuti (najmä suchého sirupu), ktorá obsahuje liečivo nepríjemnej chuti, vyšší polymér rozpustný v žalúdku (najmä AEA a Eudragit E) a monoglycerid s nízkym bodom topenia (najmä glyceryl monostearát) v stabilnej kryštalickej forme β (transformovanej z metastabilnej formy a prídavným trasením pri zvýšenej teplote) a spôsob maskovania chuti.WO 96/34628 discloses an oral pharmaceutical compound (also with macrolides) for masking taste (especially dry syrup) which contains an unpleasant taste drug, a higher stomach-soluble polymer (especially AEA and Eudragit E) and a low melting point monoglyceride (especially glyceryl monostearate) ) in a stable crystalline form of β (transformed from a metastable form and additional shaking at elevated temperature) and a taste masking method.
WO 97/16174 opisuje proces vodnej granulácie makrolidových antibiotík s karbomérom (akrylický polymér).WO 97/16174 describes a process for the aqueous granulation of macrolide antibiotics with a carbomer (acrylic polymer).
US 5,705,190 opisuje pevnú orálnu farmaceutickú zlúčeninu s kontrolovaným uvoľňovaním(aj claritromycínu) obsahujúcu liečivo slabo rozpustné vo vode, vo vode rozpustnú alginátovú soľ, zloženú soľ algínovej kyseliny s katiónom kovu a organickej karboxylovej kyseliny, ktorá umožňuje rozpúšťanie liečiva.US 5,705,190 discloses a solid oral controlled release pharmaceutical compound (including clarithromycin) containing a poorly water-soluble drug, a water-soluble alginate salt, a compound cation of an alginic acid with a metal cation and an organic carboxylic acid that allows drug dissolution.
US 5,707,646 opisuje farmaceutickú zlúčeninu (aj s makrolidmi) na orálne užívanie (najmä suchý sirup) obsahujúcu liečivo nepríjemnej chuti, funkčný polymér (najmä AEA alebo/ a Eudrgit E) v látke s bodom topenia 40-120 °C a alkohol cukru (napr. sorbitol) a základný oxid (najmä MgO).US 5,707,646 discloses a pharmaceutical compound (also with macrolides) for oral use (especially dry syrup) comprising an unpleasant taste drug, a functional polymer (especially AEA and / or Eudrgit E) in a melting point of 40-120 ° C and sugar alcohol (e.g. sorbitol) and a base oxide (especially MgO).
WO 98/46239 opisuje farmaceutickú zlúčeninu s oneskoreným uvoľňovaním obsahujúcu derivát erytromycínu a hydrofilný vo vode rozpustný polymér, ktoiý má pri orálnom užívaní zlepšenú chuťovú zložku a menej tráviaco-črevných vedľajších účinkov v porovnaní s bežnou formou. Prípravná technológia zahŕňa, inter alia, vlhkú granuláciu, sušenie, osievanie a mletie.WO 98/46239 discloses a delayed release pharmaceutical compound comprising an erythromycin derivative and a hydrophilic water-soluble polymer which has an improved taste component and less digestive-intestinal side effects when compared to the conventional form. The preparation technology includes, inter alia, wet granulation, drying, sieving and grinding.
V patentovej i inej literatúre existuje množstvo publikácií zaoberajúcich sa opisom a prípravou rôznych farmaceutických zlúčenín s claritromycínom. Ale nebol nájdený žiaden písomný zdroj opisujúci taký jednoduchý proces prípravy suspenzie claritromycínu, ktorá má také jednoduché zloženie, dobrú vôňu a chuť ako aj možnosť jej vylepšenia pre diabetikov. A na dôvažok umožňuje kontrolu množstva a miesta uvoľňovania aktívnej zložky.There are numerous publications in the patent and other literature dealing with the description and preparation of various pharmaceutical compounds with clarithromycin. However, no written source has been found describing such a simple process for the preparation of a clarithromycin suspension having such a simple composition, good odor and taste as well as the possibility of improving it for diabetics. In addition, it allows control of the amount and site of release of the active ingredient.
Podstata vynálezuSUMMARY OF THE INVENTION
Cieľom súčasného vynálezu je nová orálna farmaceutická zlúčenina claritromycínu a jeho derivátov. Horká chuť claritromycínu bola prekvapujúco úspešne maskovaná potiahnutím claritromycínu, ktorý môže byť prítomný sám alebo v homogénnej zmesi s konvenčnými prísadami, látkou s nízkym bodom topenia (pod 100 °C) vytvárajúcou lipidový film. Granulát bol pripravený pri topení v mixérovom granulátori, teda jedným krokom, v jednej nádobe bez použitia akýchkoľvek rozpúšťadiel. Z granulátu sa môžu pripraviť rôzne konvenčné farmaceutické zlúčeniny ako suspenzie v koncentráciách 125 mg/5 ml a 250 mg/5 ml, tablety alebo kapsuly.It is an object of the present invention to provide a novel oral pharmaceutical compound of clarithromycin and derivatives thereof. Surprisingly, the bitter taste of clarithromycin has been successfully masked by coating clarithromycin, which may be present alone or in a homogeneous mixture with conventional additives, a low melting point (below 100 ° C) forming a lipid film. The granulate was prepared by heating in a mixer granulator, i.e. in one step, in a single container without using any solvents. Various conventional pharmaceutical compounds may be prepared from the granulate as suspensions at 125 mg / 5 ml and 250 mg / 5 ml, tablets or capsules.
Základom poťahovania môže byť claritromycín alebo jeho kombinácia s takými excipientmi ako laktóza, uhličitan vápenatý, hydrofosforečnan sodný, NaCl, kyselina citrónová, PEG alebo polyméry nerozpustné v žalúdku ako Eudragit L alebo S( 1:1 alebo 1:2 kopolymér kyseliny metacrylovej a MMA), mikrokryštalická celulóza atď. Váhový pomer claritromycínu a týchto excipientov je od 5:1 do 1:12.The coating may be based on clarithromycin or a combination thereof with such excipients as lactose, calcium carbonate, sodium hydrogen phosphate, NaCl, citric acid, PEG, or stomach-insoluble polymers such as Eudragit L or S (1: 1 or 1: 2 methacrylic acid copolymer and MMA) , microcrystalline cellulose, etc. The weight ratio of clarithromycin to these excipients is from 5: 1 to 1:12.
Ako tukovú látku takmer nerozpustnú vo vode a vytvárajúcu film je možné použiť vyššie mastné alkoholy, najlepšie stearyl, cetostearyl alebo cetylalkohol alebo vhodnú kyselinu ako napr. kyselinu stearovú či fyzikálnu zmes alebo ester niekoľkých takýchto zložiek, napr. stearyl stearát. Váhový pomer claritromycínu a týchto excipientov je od 2:1 do 1:2.Higher fatty alcohols, preferably stearyl, cetostearyl or cetyl alcohol, or a suitable acid such as e.g. stearic acid or a physical mixture or ester of several such components, e.g. stearyl stearate. The weight ratio of clarithromycin to these excipients is from 2: 1 to 1: 2.
Granulácia topením sa vykonáva tak, že zmes claritromycínu (podľa možnosti s prídavkom adjuvans) a lipidu na poťahovanie sa rozpáli v granulátori mixovaním do bodu topenia lipidovej zložky a potom sa získaný granulát pomaly ochladí. Pri finálnej príprave granulátu na suspenziu sa tiež pridávajú látky zvyšujúce viskozitu a stabilizátory ako napr. xantánová guma, guarová guma, silikagél, kremičitan horečnatohlinitý atď. Pre lepšiu chuť, vôňu a vzhľad sa môže pridať cukor, sladidlo ako napr. aspartam, dusičnan sacharózy alebo erytritol, vanilka či ovocné príchute a farbivá. Ale ani všetky uvedené aditíva na prípravu suspenzií samé o sebe nemôžu prekryť horkosť claritromycínu.Melting granulation is carried out by mixing a mixture of clarithromycin (preferably with the addition of an adjuvant) and a lipid to be coated in the granulator by mixing to the melting point of the lipid component and then slowly cooling the obtained granulate. In the final preparation of the granulate for suspension, viscosity enhancers and stabilizers such as e.g. xanthan gum, guar gum, silica gel, magnesium aluminum silicate, etc. For better taste, smell and appearance can be added sugar, sweetener such as. aspartame, sucrose nitrate or erythritol, vanilla or fruit flavors and colorings. However, not all of the above-mentioned suspending additives alone can overlap the bitterness of clarithromycin.
Farmaceutickú zlúčeninu súčasného vynálezu možno zlepšiť použitím polyolov namiesto cukru, čím sa stáva vhodným aj pre diabetikov. Na tento cieľ je možné použiť napr. xylitol a manitol a ich kombinácie s maltitolom, maltol a sorbitol. Z toho vyplýva, že s účasná farmaceutická zlúčenina reprezentuje jedinú orálnu suspenziu, ktorá nie je založená na cukre.The pharmaceutical compound of the present invention can be improved by using polyols instead of sugar, making it suitable for diabetics. For this purpose, e.g. xylitol and mannitol and combinations thereof with maltitol, maltol and sorbitol. Accordingly, the present pharmaceutical compound represents a single oral suspension that is not sugar based.
Mastné alkoholy, ako napr. stearyl alkohol majú, v pomere k ich koncentrácii, spomaľujúci účinok na uvoľňovanie aktívnej zložky z farmaceutickej zlúčeniny. Táto vlastnosť sa môže využiť na kontrolovanie množstva uvoľňovaného claritromycínu a je možné pripraviť orálnu suspenziu s oneskoreným pôsobením.Fatty alcohols such as e.g. stearyl alcohol have, in proportion to their concentration, a retarding effect on the release of the active ingredient from the pharmaceutical compound. This property can be used to control the amount of clarithromycin released and a delayed action oral suspension can be prepared.
Dodatočne alebo výberovo, aplikovaním gastrorezistentnej vrstvy na granulátovú bázu z topenia môže byť zasiahnuté miesto uvoľňovania claritromycínu v zažívacom systéme. Preto je možné použiť polyméry tvoriace gastrorezistentný poťah ako napr. šelak, ftalát acetylcelulózy, HPMC ftalát etylcelulózového latexu, polymetakryláty, atď.Additionally or selectively, by applying the gastroresistant layer to the granular melt base, the site of clarithromycin release in the digestive system may be affected. Therefore, it is possible to use polymers forming a gastroresistant coating such as e.g. shellac, acetylcellulose phthalate, HPMC ethylcellulose latex phthalate, polymethacrylates, etc.
Príklady uskutočnenia vynálezuDETAILED DESCRIPTION OF THE INVENTION
Príklad 1Example 1
V granulátori bolo homogénne zmiešaných 2 kg claritromycínu a 2 kg stearylalkoholu. Počas miešania bola zmes zohriata až na bod topenia a bol zapnutý drvič. Potom sa zmes ochladila konštantným miešaním. Vytvorili sa guľovité granuly/ pelety. Boli k nim pridané suché aditíva.2 kg of clarithromycin and 2 kg of stearyl alcohol were homogeneously mixed in the granulator. While stirring, the mixture was heated to the melting point and the crusher was started. Then the mixture was cooled by constant stirring. Spherical granules / pellets were formed. Dry additives were added.
Suché aditíva per vial alebo na 5.00 g claritromycín stearyl granulátu (pelety)Dry additives per vial or per 5.00 g clarithromycin stearyl granulate (pellets)
Proces bol identický s príkladom 1, len 1.25 kg claritromycínu, 1.25 kg kyseliny stearovej a 1.5 kg NaH2PO4 bolo homogénne zmiešaných.The process was identical to Example 1 except that only 1.25 kg of clarithromycin, 1.25 kg of stearic acid and 1.5 kg of NaH 2 PO 4 were homogeneously mixed.
Suché aditíva per vial alebo na 7.2 g potiahnutého granulátu claritromycínu (pelety)Dry additives per vial or per 7.2 g coated clarithromycin granules (pellets)
Príklad 2Example 2
Príklad 3Example 3
ΊΊ
Ak bol aplikovaný gastrorezistentný poťah, množstvo sladidla sa zredukovalo na mg, inak bola príprava finálnej suspenzie identická s príkladom 1.When a gastro-resistant coating was applied, the amount of sweetener was reduced to mg, otherwise the preparation of the final suspension was identical to Example 1.
Príklad 4Example 4
Príprava granulátu bola identická s príkladom 1 alebo 2. Naviac bol aplikovaný gastrorezistentný poťah, na 500 mg peletových jadier bola pripravená nasledujúca vodnáThe preparation of the granulate was identical to Example 1 or 2. In addition, a gastroresistant coating was applied, and the following aqueous solution was prepared for 500 mg of pellet cores.
Príprava vodnej disperzie: trietylcitrát, mastenec a činidlo zabraňujúce peneniu boli rozptýlené vo vode a homogenizované. Tesne pred použitím bola disperzia vmiešané do disperzie Eudragitu a toto bolo prefiltrované .Preparation of the aqueous dispersion: triethyl citrate, talc and antifoaming agent were dispersed in water and homogenized. Just before use, the dispersion was mixed into the Eudragit dispersion and this was filtered.
Claims (14)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SI9900119A SI20244A (en) | 1999-05-19 | 1999-05-19 | Melt granulation |
| PCT/SI2000/000013 WO2000069415A2 (en) | 1999-05-19 | 2000-05-18 | Melt granulation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SK16642001A3 true SK16642001A3 (en) | 2002-05-09 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK1664-2001A SK16642001A3 (en) | 1999-05-19 | 2000-05-18 | Pharmaceutical formulation in granular form |
Country Status (13)
| Country | Link |
|---|---|
| EP (1) | EP1183013A2 (en) |
| AU (1) | AU4969700A (en) |
| BG (1) | BG106236A (en) |
| CZ (1) | CZ20014133A3 (en) |
| EE (1) | EE200100607A (en) |
| HR (1) | HRP20010932A2 (en) |
| HU (1) | HUP0201233A3 (en) |
| PL (1) | PL351654A1 (en) |
| RU (1) | RU2001134166A (en) |
| SI (1) | SI20244A (en) |
| SK (1) | SK16642001A3 (en) |
| WO (1) | WO2000069415A2 (en) |
| YU (1) | YU82001A (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK1267840T3 (en) * | 2000-03-28 | 2009-09-07 | Sandoz Ag | Granulated particles with masked taste |
| MXPA03003146A (en) * | 2000-10-13 | 2004-12-06 | Advancis Pharmaceuticals | Extended release erythromycin derivatives. |
| AU2003211243B8 (en) | 2002-02-21 | 2008-11-06 | Otsuka Pharmaceutical Co., Ltd. | Sustained release preparations and process for producing the same |
| US7943585B2 (en) | 2003-12-22 | 2011-05-17 | Sandoz, Inc. | Extended release antibiotic composition |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2085342A1 (en) * | 1990-06-14 | 1991-12-15 | Milton R. Kaplan | Stable aqueous drug suspensions |
| JP3265680B2 (en) * | 1992-03-12 | 2002-03-11 | 大正製薬株式会社 | Oral pharmaceutical composition |
| EP0670716B1 (en) * | 1992-11-30 | 2003-03-26 | Kv Pharmaceutical Company | Tastemasked pharmaceutical materials |
| IT1312058B1 (en) * | 1999-04-09 | 2002-04-04 | Pharmaplus S R L | METHOD FOR MICRO-ENCAPSULATION OF MEDICATIONS. |
-
1999
- 1999-05-19 SI SI9900119A patent/SI20244A/en not_active IP Right Cessation
-
2000
- 2000-05-18 WO PCT/SI2000/000013 patent/WO2000069415A2/en not_active Application Discontinuation
- 2000-05-18 PL PL00351654A patent/PL351654A1/en not_active Application Discontinuation
- 2000-05-18 CZ CZ20014133A patent/CZ20014133A3/en unknown
- 2000-05-18 SK SK1664-2001A patent/SK16642001A3/en unknown
- 2000-05-18 AU AU49697/00A patent/AU4969700A/en not_active Abandoned
- 2000-05-18 RU RU2001134166/14A patent/RU2001134166A/en not_active Application Discontinuation
- 2000-05-18 EE EEP200100607A patent/EE200100607A/en unknown
- 2000-05-18 HU HU0201233A patent/HUP0201233A3/en unknown
- 2000-05-18 YU YU82001A patent/YU82001A/en unknown
- 2000-05-18 EP EP00931886A patent/EP1183013A2/en not_active Withdrawn
-
2001
- 2001-12-18 HR HR20010932A patent/HRP20010932A2/en not_active Application Discontinuation
- 2001-12-19 BG BG106236A patent/BG106236A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| WO2000069415A2 (en) | 2000-11-23 |
| SI20244A (en) | 2000-12-31 |
| EE200100607A (en) | 2003-02-17 |
| HUP0201233A3 (en) | 2003-10-28 |
| YU82001A (en) | 2004-07-15 |
| CZ20014133A3 (en) | 2002-03-13 |
| BG106236A (en) | 2002-08-30 |
| AU4969700A (en) | 2000-12-05 |
| WO2000069415A3 (en) | 2001-04-26 |
| HRP20010932A2 (en) | 2003-04-30 |
| RU2001134166A (en) | 2003-08-27 |
| EP1183013A2 (en) | 2002-03-06 |
| PL351654A1 (en) | 2003-05-19 |
| HUP0201233A2 (en) | 2002-08-28 |
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