SE522851C2 - Kortikoidkomposition - Google Patents
KortikoidkompositionInfo
- Publication number
- SE522851C2 SE522851C2 SE9404280A SE9404280A SE522851C2 SE 522851 C2 SE522851 C2 SE 522851C2 SE 9404280 A SE9404280 A SE 9404280A SE 9404280 A SE9404280 A SE 9404280A SE 522851 C2 SE522851 C2 SE 522851C2
- Authority
- SE
- Sweden
- Prior art keywords
- release
- corticoid
- weight
- pharmaceutical composition
- hour
- Prior art date
Links
- 239000003470 adrenal cortex hormone Substances 0.000 claims description 12
- RKHQGWMMUURILY-UHRZLXHJSA-N cortivazol Chemical compound C([C@H]1[C@@H]2C[C@H]([C@]([C@@]2(C)C[C@H](O)[C@@H]1[C@@]1(C)C2)(O)C(=O)COC(C)=O)C)=C(C)C1=CC1=C2C=NN1C1=CC=CC=C1 RKHQGWMMUURILY-UHRZLXHJSA-N 0.000 claims description 12
- 229960005205 prednisolone Drugs 0.000 claims description 12
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 claims description 12
- 239000013543 active substance Substances 0.000 claims description 8
- 239000008363 phosphate buffer Substances 0.000 claims description 7
- 239000011248 coating agent Substances 0.000 claims description 6
- 238000000576 coating method Methods 0.000 claims description 6
- 210000004051 gastric juice Anatomy 0.000 claims description 6
- 239000003862 glucocorticoid Substances 0.000 claims description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 6
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 5
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 claims description 5
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 claims description 5
- 229960004618 prednisone Drugs 0.000 claims description 5
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 claims description 5
- 230000003111 delayed effect Effects 0.000 claims description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 4
- 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 claims description 3
- 229920002472 Starch Polymers 0.000 claims description 3
- 239000008101 lactose Substances 0.000 claims description 3
- 239000000314 lubricant Substances 0.000 claims description 3
- 235000019359 magnesium stearate Nutrition 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 210000000813 small intestine Anatomy 0.000 claims description 3
- 239000008107 starch Substances 0.000 claims description 3
- 235000019698 starch Nutrition 0.000 claims description 3
- 210000002784 stomach Anatomy 0.000 claims description 3
- 239000000454 talc Substances 0.000 claims description 3
- 229910052623 talc Inorganic materials 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims 7
- 206010011878 Deafness Diseases 0.000 claims 1
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 239000003814 drug Substances 0.000 description 7
- 229940079593 drug Drugs 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 208000002193 Pain Diseases 0.000 description 3
- 210000003743 erythrocyte Anatomy 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 210000000265 leukocyte Anatomy 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 229940037128 systemic glucocorticoids Drugs 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- 229920003134 Eudragit® polymer Polymers 0.000 description 2
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 208000006820 Arthralgia Diseases 0.000 description 1
- 101710169603 Hemoglobin-1 Proteins 0.000 description 1
- 238000000585 Mann–Whitney U test Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 208000018937 joint inflammation Diseases 0.000 description 1
- 208000018934 joint symptom Diseases 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 230000000422 nocturnal effect Effects 0.000 description 1
- -1 prednisolone Chemical compound 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000002618 waking effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0065—Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
-
- 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
- A61K9/2022—Organic macromolecular compounds
- A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
-
- 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
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- 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
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
20 25 *tio ÄÉ5 5 2 2 8 5 1 _ l mängd av åtminstone en kortikoid, evéntuešllti kbmbinatión med sédvanfigerf 'an-" vända spädnings-och hjälpmedel överdrages med en frisättningsfördröjande substans eller komposition, varvid kompositionen i ett frisättningstest enligt US Pharmacopea Standards (USP XXI, apparat 2, 100 rpm) i artificiell magsaft, med ett pH av upp till 1,2 ger en frisättning av kortikoid av högst 10 vikt-% under 1 hr, och i enlighet med samma standardfrisättningsmetod i en fosfatbuffert med pH 6,8 frisätter minst 80 vikt-% inom 3 hrs. The amount of at least one corticoid, optionally combined with diluents and diluents used is coated with a release-delaying substance or composition, the composition in a release test according to US Pharmacopea Standards ( USP XXI, apparatus 2, 100 rpm) in artificial gastric juice, with a pH of up to 1.2 gives a release of corticoid of not more than 10% by weight for 1 hr, and according to the same standard release method in a phosphate buffer of pH 6, 8 releases at least 80% by weight within 3 hrs.
Enligt en annan aspekt av föreliggande uppfinning ästadkommes en metod för behandling av inflammatoriska tillstånd och/eller symptom, varvid en terapeutiskt effektiv mängd av minst en kortikoid administreras vid en sådan tidpunkt att re- sorption av den aktiva substansen sker under dygnets sömn/viloperiod, och fö- reträdesvis så att resorption sker 4-5 hrs före uppvaknandet.According to another aspect of the present invention there is provided a method of treating inflammatory conditions and / or symptoms, wherein a therapeutically effective amount of at least one corticoid is administered at such a time that resorption of the active substance occurs during the sleep / rest period of the day, and preferably so that resorption takes place 4-5 hrs before awakening.
Med terapeutisk mängd avses här normalt en dos som ligger avsevärt under den generellt använda enligt beprövad praxis för behandling av ett specifikt tillstånd.By therapeutic amount is here normally meant a dose which is considerably below the generally used according to proven practice for the treatment of a specific condition.
Genom föreliggande uppfinning uppnås att den effektiva dosnivån kan reduce- ras med 75-80% baserat på den dosnnivå som hittills generellt använts.The present invention achieves that the effective dose level can be reduced by 75-80% based on the dose level generally used heretofore.
Uppfinningen kommer nedan att beskrivas med hänvisning till genomförda för- sök och exempel.The invention will be described below with reference to performed experiments and examples.
Behandlingseffekten av peroral tillförsel av administrerade glukokortikoider till 26 patienter med reumatoid artrit studerades. Sex av patienterna var män i åldern 54-80 år, medelålder 69 år och 20 var kvinnor i åldern 23-90 år, medelålder 62 år. Patienterna delades slumpmässigt in i två grupper. Grupp A erhöll glukokor- tikoider (Prednisolon) på natten kl. 02.00 och grupp B erhöll prednisolon kl.07.30. l grupp A ingick 13 patienter liksom i grupp B. l vardera gruppen erhöll 4 patienter 7,5 mg prednisolon och 9 patienter 5 mg prednisolon. Alla patienter er- höll sammanlagt 4 doser prednisolon under 4 dygn. Varje patient undersöktes kliniskt före försökets början och efter avslutad behandling med avseende på varaktigheten av morgonstelhet, graden av ledsmärta avläst med en 10-gradig skala och ledindex, s.k. Lansburys index som bedömer graden av ledinflamma- tion. Det visade sig att den grupp patienter som erhållit prednisolon på natten 10 15 20 25 'Pào » :o u n o .i u »>»» 522 851 3 hade i genomsnitt en 5-faldig förbättririgax: rmrgdnstelhëteri, en ßïfafäig för-'f " bättring av vilosmàrtan och en 4-faldig förbättring av ledindex. Effekterna var statitiskt säker-ställda. I den patientgrupp som erhöll prednisolon på morgonen sågs ej någon effekt på vilosrnärta eller ledindex, utan blott en marginell, cza 20%-ig förbättring av morgonstelheten. Skillnaderna i effekt mellan de båda patientgrupperna var statistiskt säker för de olika variablerna.The therapeutic effect of oral administration of administered glucocorticoids to 26 patients with rheumatoid arthritis was studied. Six of the patients were men aged 54-80 years, mean age 69 years and 20 were women aged 23-90 years, mean age 62 years. The patients were randomly divided into two groups. Group A received glucocorticoids (Prednisolone) at night at 02.00 and group B received prednisolone at 07.30. Group A included 13 patients as well as group B. In each group, 4 patients received 7.5 mg prednisolone and 9 patients received 5 mg prednisolone. All patients received a total of 4 doses of prednisolone over 4 days. Each patient was examined clinically before the start of the trial and after the end of treatment with regard to the duration of morning stiffness, the degree of joint pain read with a 10-point scale and joint index, so-called Lansbury's index, which assesses the degree of joint inflammation. It was found that the group of patients who received prednisolone at night 10 15 20 25 'Pào »: ouno .iu»> »» 522 851 3 had on average a 5-fold improvement gax: rmrgdnstelhëteri, a ßïfafäig for-'f "improvement of the pain of rest and a 4-fold improvement in joint index.The effects were statically assured.In the patient group receiving prednisolone in the morning, no effect on rest pain or joint index was seen, but only a marginal, cza 20% improvement in morning stiffness. effect between the two patient groups was statistically significant for the different variables.
Försöket visar sålunda att samma dos av ett glukokortikoidpreparat men given vid olika tidpunkter på dygnet ger dramatiskt olika effekt på ledsymptomen vid reumatoid artrit. Att nattlig tillförsel av glukokortikoider på ett så dramatiskt sätt kan påverka sjukdomssymptomen av reumatoid artrit har tidigare inte påvisats eller beskrivits. Resultaten visar att en given mängd glukokortikoid kan reduceras med en faktor 3-4 om läkemedlet administreras på natten, eller i vart fall absor- beras på natten, jämfört med etablerad dosering på morgonen.The experiment thus shows that the same dose of a glucocorticoid preparation but given at different times of the day has dramatically different effects on the joint symptoms of rheumatoid arthritis. That nocturnal administration of glucocorticoids in such a dramatic way can affect the disease symptoms of rheumatoid arthritis has not been previously proven or described. The results show that a given amount of glucocorticoid can be reduced by a factor of 3-4 if the drug is administered at night, or at least absorbed at night, compared with established dosing in the morning.
Erhållna resultat visas i tabeilen nedan, varvid visas kliniska och laboratoriedata hos de 26 patienterna med reumatoid artrit vid dag 1 och efter 4 doser av predni- solon (dag 5). 10 15 20 25 'Prio . i.The results obtained are shown in the table below, showing clinical and laboratory data in the 26 patients with rheumatoid arthritis at day 1 and after 4 doses of prednisolone (day 5). 10 15 20 25 'Prio. in.
I I l -~35 'II li 522 851 Tabell . _ Dag 1 Dag 5 kl. 02.00 kl.07.30 kl. 02.00 kl.07.30 (n=13) (n=13) (n=13) (n=13) Ålder 6214 6415 Sjukdomstld 1 013 1 214 Morgonstelhet 242138 3071103 53127 ** 2601104 Vilosmärta 4,010,7 3,510,6 1,510,4 * 3,410,7 Lansbury index 130123 101119 3317 ** 8711 3 Ritchie index 2113 1612 1 112 1412 ESR (mm/hr) 4719 4115 3615 3114 Haptoglogin (g/l) 2,810,3 2,310,3 2,710,3 2,310,3 Hemoglobin 1 1515 1 2313 1 1815 12313 WBC x 109 7,010,4 7,010,6 7,210,4 7,410,5 FlBC x 109 308118 * 256114 336124 276115 ESR: erytrocytsedimenteringshastighet (sänka) WBC: vita blodkroppar RBC: röda blodkroppar * p<0,05; ** p<0,01 med Mann-Whitney U-test.I I l - ~ 35 'II li 522 851 Table. _ Day 1 Day 5 p.m. 02.00 kl.07.30 kl. 02.00 kl.07.30 (n = 13) (n = 13) (n = 13) (n = 13) Age 6214 6415 Sickness 1 013 1 214 Morning stiffness 242138 3071103 53127 ** 2601104 Resting pain 4,010.7 3,510.6 1,510.4 * 3,410.7 Lansbury index 130123 101119 3317 ** 8711 3 Ritchie index 2113 1612 1 112 1412 ESR (mm / hr) 4719 4115 3615 3114 Haptoglogin (g / l) 2,810.3 2,310.3 2,710.3 2,310.3 Hemoglobin 1 1515 1 2313 1 1815 12313 WBC x 109 7,010.4 7,010,6 7,210,4 7,410,5 FlBC x 109 308118 * 256114 336124 276115 ESR: erythrocyte sedimentation rate (decrease) WBC: white blood cells RBC: red blood cells * p <0.05; ** p <0.01 with Mann-Whitney U test.
Det är uppenbart för fackmannen att andra inflammatoriska sjukdomstillstånd och/eller deras symptom kan behandlas på samma sätt, dvs med en reducerad dosmängd given på natten för att därmed bl. a. förbättra dossvaret och/eller redu- cera biverkningsfrekvensen av det givna läkemedlet.It is obvious to the person skilled in the art that other inflammatory disease states and / or their symptoms can be treated in the same way, ie with a reduced dose given at night so that e.g. a. improve the dose response and / or reduce the frequency of side effects of the given medicine.
En lämplig beredningsform för peroral administrering för att kunna genomföra en sådan behandling innebär att läkemedlet skall administreras före normalt säng- gående, eftersom det är obekvämt att stiga upp mitt i natten under bästa sömn för att intaga sitt läkemedel. Detta innebär i sin tur att làkemedelsberedningen måste omfatta en fördröjd frisättning av det aktuella terapeutiska medlet så att det resor- beras i den intestinala trakten först vid 2-3-tiden på natten. Prednisolon liksom prednison, ett annat läkemedel mot reumatoid artrit resorberas mycket snabbt 10 15 20 25 II r I . '35 . 522 ast I 5 och uppvisar normalt en plasma toppkåncætratibn inom-*l-S hrs. oèh 'en-plasma " halveringstid av 2-3,5 hrs.A suitable form of oral administration to be able to carry out such treatment means that the drug should be administered before normal bedtime, as it is inconvenient to get up in the middle of the night during the best sleep to take the drug. This in turn means that the drug preparation must include a delayed release of the therapeutic agent in question so that it is resorbed in the intestinal tract only at 2-3 o'clock at night. Prednisolone as well as prednisone, another drug for rheumatoid arthritis are very rapidly resorbed. '35. 522 ast I 5 and normally exhibits a plasma peak cannabatibine within- * 1-S hrs. oèh 'en-plasma "half-life of 2-3.5 hrs.
Exempel En kärna omfattande prednisolon en terapeutisk mängd belades med ett skikt av hydroxipropylmetylcellulosaftalat (HPSS) i en mängd av 8 vikt-% baserat på den totala vikten av kompositionen.Example A core comprising prednisolone a therapeutic amount was coated with a layer of hydroxypropyl methylcellulose phthalate (HPSS) in an amount of 8% by weight based on the total weight of the composition.
Kompositionen uppvisar en frisättningshastighet med avseende på aktiv subs- tans som är mindre än 10 vikt-% under de första två timmarna i sur artificiell mag- saft, pH 1,2, och som är upp till 100 vikt-% inom två timmar i fosfatbuffert, pH 6,8.The composition exhibits an active substance release rate of less than 10% by weight during the first two hours in acidic artificial gastric juice, pH 1.2, and up to 100% by weight within two hours in phosphate buffer. , pH 6.8.
Enligt en föredragen utföringsform är frisättningen fördröjd till 1-3 timmar efter passage av magen till tunntarmen, vilket innebär att en tablett eller granulat skall motstå frisättning under 2 hrs i 0,1 N HCl, varefter tabletten eller granulatet skall vidare kunna motstå frisättning under 2 hrs i fosfatbuffert vid pH 6,8, varefter in- nehållet skall frisättas under 1 hr. Detta utgör en optimal frisättningsprofil, men även mindre optimala profiler är tillämpliga så länge som tillslag av aktiv be- ståndsdel sker 4-5 hrs före ett uppvaknande, i allmänhet kl. 02--03 på morgonen.According to a preferred embodiment, the release is delayed to 1-3 hours after passage of the stomach to the small intestine, which means that a tablet or granulate should resist release for 2 hrs in 0.1 N HCl, after which the tablet or granulate should further be able to resist release for 2 hours. hrs in phosphate buffer at pH 6.8, after which the contents should be released for 1 hr. This constitutes an optimal release profile, but even less optimal profiles are applicable as long as the activation of the active ingredient takes place 4-5 hrs before waking up, generally at 02--03 in the morning.
För att uppnå detta med den lilla verksamma mängden, 5 mg, bör substansen mikroniseras och våtgranuleras. Ett sådant granulat har en frisättningshastighet i sig på 70% under 30 min i 37°C vatten. Förutom ovan nämnda överdrag kan ett laminatöverdrag med ett inre skikt av en pH 6,8 delvis resistent typ, såsom Eudragit (varumärke) RL och med ett yttre skikt för att motstå pH 1 passagen av Eudragit (varumärke) L.To achieve this with the small effective amount, 5 mg, the substance should be micronized and wet granulated. Such a granulate has a release rate per se of 70% for 30 minutes in 37 ° C water. In addition to the above coating, a laminate coating having an inner layer of a pH 6.8 partially resistant type, such as Eudragit (trademark) RL and having an outer layer to resist the pH 1 passage of Eudragit (trademark) L.
Den aktiva beståndsdelen av kortikoid såsom prednisolon, uppblandas lämpli- gen med kända spädningsmedel, såsom stärkelse, laktos, och granuleras med PVP (polyvinylpyrrolidon). För tablettslagning tillsättes glidmedel såsom talk och magnesiumstearat.The active ingredient of corticoid, such as prednisolone, is suitably mixed with known diluents such as starch, lactose, and granulated with PVP (polyvinylpyrrolidone). For tableting, lubricants such as talc and magnesium stearate are added.
O UontvtO Uontvt
Claims (13)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9404280A SE522851C2 (en) | 1994-12-09 | 1994-12-09 | Kortikoidkomposition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9404280A SE522851C2 (en) | 1994-12-09 | 1994-12-09 | Kortikoidkomposition |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SE522851C2 true SE522851C2 (en) | 2004-03-09 |
Family
ID=31885307
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SE9404280A SE522851C2 (en) | 1994-12-09 | 1994-12-09 | Kortikoidkomposition |
Country Status (1)
| Country | Link |
|---|---|
| SE (1) | SE522851C2 (en) |
-
1994
- 1994-12-09 SE SE9404280A patent/SE522851C2/en not_active IP Right Cessation
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