NO168627B - PROCEDURE FOR THE PREPARATION OF QUICK-RELEASE DIHYDROPYRIDINE PREPARATION. - Google Patents
PROCEDURE FOR THE PREPARATION OF QUICK-RELEASE DIHYDROPYRIDINE PREPARATION. Download PDFInfo
- Publication number
- NO168627B NO168627B NO843772A NO843772A NO168627B NO 168627 B NO168627 B NO 168627B NO 843772 A NO843772 A NO 843772A NO 843772 A NO843772 A NO 843772A NO 168627 B NO168627 B NO 168627B
- Authority
- NO
- Norway
- Prior art keywords
- dihydropyridine
- quick
- compound
- preparation
- solid dispersion
- Prior art date
Links
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 title claims description 25
- 238000002360 preparation method Methods 0.000 title claims description 25
- 238000000034 method Methods 0.000 title claims description 9
- 150000001875 compounds Chemical class 0.000 claims description 25
- 239000007962 solid dispersion Substances 0.000 claims description 18
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 13
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 13
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 13
- 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 claims description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- 239000003960 organic solvent Substances 0.000 claims description 8
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- 239000000725 suspension Substances 0.000 claims description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- 235000019441 ethanol Nutrition 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims 2
- 239000003826 tablet Substances 0.000 description 15
- 239000008187 granular material Substances 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 230000036470 plasma concentration Effects 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 239000007941 film coated tablet Substances 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
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 238000007922 dissolution test Methods 0.000 description 3
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 2
- 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 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 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
- 239000011247 coating layer Substances 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 229920002584 Polyethylene Glycol 6000 Polymers 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- YKTSYUJCYHOUJP-UHFFFAOYSA-N [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] Chemical compound [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] YKTSYUJCYHOUJP-UHFFFAOYSA-N 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 229940093429 polyethylene glycol 6000 Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Description
Denne oppfinnelse angår fremstilling av et hurtig-frigjørende fast preparat som inneholder dihydropyridin A forbindelsen [isopropyl-6-cyano-5-metoksykarbonyl-2-metyl-4-(3-nitrofenyl)-1,4-dihydropyridin-3-karboksylat], som har den følgende kjemiske formel: This invention relates to the preparation of a fast-release solid preparation containing the dihydropyridine A compound [isopropyl-6-cyano-5-methoxycarbonyl-2-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate], which has the following chemical formula:
Denne forbindelse er kjent fra DE 2.940.833 (krav 19). Hurtig-frigjørende faste prepreparater er bl.a. kjent fra This compound is known from DE 2,940,833 (claim 19). Quick-release solid preparations include known from
DE 3.013.839, JP Kokai nr. 58-77811 og JP Kokai nr.58-109412. DE 3,013,839, JP Kokai No. 58-77811 and JP Kokai No. 58-109412.
Dihydropyridin A forbindelsen viser karutvidende virk-ninger såsom hjerte-karutvidende virkning, hypotensiv virkning eller lignende, og er således nyttig for behandling av hjerte-karsykdommer såsom hjertesvikt, angina pektoris, myokardialt infarkt eller lignende, eller hypertensjon. The dihydropyridine A compound shows vasodilating effects such as cardiovasodilating effect, hypotensive effect or the like, and is thus useful for the treatment of cardiovascular diseases such as heart failure, angina pectoris, myocardial infarction or the like, or hypertension.
Ved oral administrering er imidlertid forholdet mellom absorpsjonen av dihydropyridin A forbindelsen i blodet og dens dose utilstrekkelig på grunn av dens dårlige oppløselig-het i vann (praktisk talt uoppløselig), og dihydropyridin A forbindelsen har således den ulempe at den er dårlig biologisk tilgjengelig. When administered orally, however, the ratio between the absorption of the dihydropyridine A compound in the blood and its dose is insufficient due to its poor solubility in water (practically insoluble), and the dihydropyridine A compound thus has the disadvantage that it is poorly biologically available.
Oppfinnerne av foreliggende oppfinnelse har funnet at nevnte ulempe kan avhjelpes ved dispergering av dihydropyridin A forbindelsen med hydroksypropylmetyl-cellulose, for å fremstille et hurtig-frigjørende, fast dispersjonspreparat og kom frem til foreliggende oppfinnelse. The inventors of the present invention have found that said disadvantage can be remedied by dispersing the dihydropyridine A compound with hydroxypropylmethyl cellulose, to produce a quick-release, solid dispersion preparation and arrived at the present invention.
Foreliggende oppfinnelse skal forklares i mer detalj i det følgende. The present invention will be explained in more detail below.
Det hurtig-frigjørende faste dispersjonspreparat fremstilles ved at dihydropyridin A forbindelsen oppløses i et egnet organisk oppløsningsmiddel, til den resulterende opp-løsning settes hydroksyprbpylmetylcellulose for å fremstille en homogen suspensjon, og derefter avdampes det organiske oppløsningsmiddel på vanlig måte. The quick-release solid dispersion preparation is prepared by dissolving the dihydropyridine A compound in a suitable organic solvent, adding hydroxypropylmethylcellulose to the resulting solution to produce a homogeneous suspension, and then evaporating the organic solvent in the usual way.
De organiske oppløsningsmidler som anvendes ved denne fremgangsmåte er ikke begrenset, og et hvilket som helst oppløsningsmiddel som dihydropyridin A forbindelsen kan opp-løses i, kan anvendes. Egnede eksempler på dette oppløsnings-middel kan omfatte kloroform, metylenklorid, aceton, etylacetat, alkohol (for eksempel metanol, etanol osv.) og lignende. The organic solvents used in this method are not limited, and any solvent in which the dihydropyridine A compound can be dissolved can be used. Suitable examples of this solvent may include chloroform, methylene chloride, acetone, ethyl acetate, alcohol (for example methanol, ethanol, etc.) and the like.
Hydroksypropylmetylcellulose er en av de vannoppløselige polymerer, og den anvendes for å dispergere dihydropyridin A forbindelsen for å danne et hurtig-frigjørende fast dispersjonspreparat. Hydroxypropyl methylcellulose is one of the water-soluble polymers, and it is used to disperse the dihydropyridine A compound to form a quick-release solid dispersion preparation.
Mengden av hydroksypropylmetylcellulose som anvendes, The amount of hydroxypropylmethylcellulose used,
er ikke gjenstand for noen begrensning, og en hvilken som helst mengde som dihydropyridin A forbindelsen kan dispergeres av, kan anvendes, og fortrinnsvis anvendes tre til syv ganger så mye som dihydropyridin A forbindelsen, basert på vekt. is not subject to any limitation, and any amount by which the dihydropyridine A compound can be dispersed may be used, and preferably three to seven times as much as the dihydropyridine A compound, based on weight, is used.
Det nye hurtig-frigjørende faste dispersjonspreparat fremstilt ved ovennevnte fremgangsmåte ifølge oppfinnelsen, kan anvendes alene som et hurtig-frigjørende fast preparat og kan omdannes til forskjellige doseringsformer såsom pulvere, fine granuler, granuler, tabletter eller lignende, på vanlig måte. Eventuelt kan farvemidler, søtningsmidler, smaksstoffer, for-tynningsmidler (for eksempel sukrose, laktose, stivelse, krystallinsk cellulose, lav-susbtituert hydroksypropylcellulose, syntetisk aluminiumsilikat osv.), smøremiddel (for eksempel magnesiumstearat osv.) eller lignende, dispergeres sammen med nevnte hurtig-frigjørende faste dispersjonspreparat. The new quick-release solid dispersion preparation produced by the above-mentioned method according to the invention can be used alone as a quick-release solid preparation and can be converted into different dosage forms such as powders, fine granules, granules, tablets or the like, in the usual way. Optionally, coloring agents, sweeteners, flavors, diluents (for example sucrose, lactose, starch, crystalline cellulose, low-substituted hydroxypropyl cellulose, synthetic aluminum silicate, etc.), lubricants (for example magnesium stearate, etc.) or the like can be dispersed together with said rapid -releasing solid dispersion preparation.
Det hurtig-frigjørende faste dispersjonspreparat og de forskjellige medisinske preparater som kan fremstilles ved eventuelt å omdanne nevnte hurtig-frigjørende, faste dispersjonspreparat til forskjellige doseringsformer som nevnt ovenfor, The quick-release solid dispersion preparation and the various medicinal preparations that can be prepared by optionally converting said quick-release solid dispersion preparation into different dosage forms as mentioned above,
har en bemerkelsesverdig forbedret oppløselighet og absorpsjons-evne i blodet sammenlignet med dihydropyridin A forbindelsen som sådan. has a remarkably improved solubility and absorbability in the blood compared to the dihydropyridine A compound as such.
For å forbedre stabiliteten, gjøre utseendet bedre, gjøre overflaten glattere, forbedre administreringsegenskapene og lignende, kan eventuelt det hurtig-frigjørende faste dispersjonspreparat fremstilt ovenfor anvendes for eksempel som en filmbelagt tablett. In order to improve the stability, make the appearance better, make the surface smoother, improve the administration properties and the like, the quick-release solid dispersion preparation prepared above can optionally be used, for example, as a film-coated tablet.
Nevnte filmbelagte tablett kan fremstilles ved at ovennevnte tablett belegges på vanlig måte, idet belegg-laget kan Said film-coated tablet can be produced by coating the above-mentioned tablet in the usual way, as the coating layer can
inneholde hydroksypropylmetylcellulose. contain hydroxypropylmethylcellulose.
For å vise de gode egenskaper hos det hurtig-frigjørende faste preparat fremstilt ifølge oppfinnelsen, henvises til de følgende forsøksresultater. To show the good properties of the quick-release solid preparation produced according to the invention, reference is made to the following test results.
OppløsningsundersøkeIse Resolution investigationIse
[Forsøksprøve] [Trial sample]
(1) De fine granuler beskrevet i det følgende eksempel 2 (1) The fine granules described in the following example 2
(2) Tabletten beskrevet i det følgende eksempel 3 (2) The tablet described in the following example 3
(3) Den filmbelagte tablett beskrevet i det følgende eksempel 4. (3) The film-coated tablet described in the following example 4.
[Forsøksmetode] [Test method]
Forsøkene ble utført i henhold til metode 2 (skovl-metoden) fra oppløsningsforsøket i den japanske Pharmacopoeia (10. utgave) under anvendelse av vann som forsøksoppløsning, og oppløsningsgraden efter 15 minutter fra begynnelsen av hvert oppløsningsforsøk ble målt. The experiments were carried out according to method 2 (scoop method) from the dissolution test in the Japanese Pharmacopoeia (10th edition) using water as the test solution, and the degree of dissolution after 15 minutes from the beginning of each dissolution test was measured.
[Forsøksresultater] [Experimental Results]
Fra resultatene av oppløsningsforsøket viste det seg at et hvilket som helst hurtig-frigjørende fast preparat som inneholder det hurtig-frigjørende faste dispersjonspreparat av dihydropyridin A forbindelsen, oppviste meget god opp-løsningshastighet. From the results of the dissolution test, it appeared that any fast-release solid preparation containing the fast-release solid dispersion preparation of the dihydropyridine A compound showed a very good dissolution rate.
Plasmakonsentrasjonsforsøk Plasma concentration test
[Forsøksprøve] [Trial sample]
(1) Tabletten beskrevet i det følgende eksempel 3 (1) The tablet described in the following example 3
(denne tablett inneholder 2 mg av dihydropyridin A (this tablet contains 2 mg of dihydropyridine A
forbindelsen i en tablett). the compound in a tablet).
(2) Sammenligningstablett: (2) Comparison tablet:
Tabletter som hver hadde den nedenfor angitte sammensetning, ble fremstilt på vanlig måte (våt-granulerings-metode), og de ble anvendt som sammenlignings-tabletter ved dette forsøk. Tablets, each of which had the composition indicated below, were prepared in the usual way (wet granulation method), and they were used as comparison tablets in this experiment.
Sammensetning av sammenligningstablett Composition of comparison tablet
[Forsøksmetode] [Test Method]
Den mengde tabletter som tilsvarte 10 mg av dihydropyridin A forbindelsen [dvs. 5 tabletter av forsøksprøve (1) The quantity of tablets corresponding to 10 mg of the dihydropyridine A compound [i.e. 5 tablets of experimental sample (1)
og 1 tablett av forsøksprøve (2)] ble administrert oralt til seks beagle-hunder (8-12 kg), som var holdt vekk fra mat natten over på en slik måte at man fikk et dekkende resultat. Plasmakonsentrasjonen av dihydropyridin A forbindelsen ble bestemt ved gasskromatografi med ECD ved 0,5, 1, 2, 4, 6, 8, 10, 12 and 1 tablet of test sample (2)] was administered orally to six beagle dogs (8-12 kg), which were kept away from food overnight in such a way that a comprehensive result was obtained. The plasma concentration of the dihydropyridine A compound was determined by gas chromatography with ECD at 0.5, 1, 2, 4, 6, 8, 10, 12
og 24 timer efter administreringen. and 24 hours after administration.
[Forsøksresultater] [Experimental Results]
Plasmakonsentrasjonen på hvert tidspunkt, maksimum plasmakonsentrasjon (C maks)- og; arealet under plasmakonsentrasjonen-tid-kurven (AUC) i hvert tilfelle med forsøksprøve (1) og forsøksprøve (2) er vist i den følgende tabell. The plasma concentration at each time, maximum plasma concentration (C max)- and; the area under the plasma concentration-time curve (AUC) in each case of test sample (1) and test sample (2) is shown in the following table.
Hver verdi er representert ved [middelverdien + standard avvik] for seks beagle-hunder. Each value is represented by the [mean + standard deviation] of six beagle dogs.
Som det fremgår av tabellen, både med hensyn til maksimum plasmakonsentrasjon og arealet under plasma-konsentras jon-tid-kurven , viste forsøksprøve (1) seg å være vesentlig bedre enn forsøksprøve (2). As can be seen from the table, both with regard to maximum plasma concentration and the area under the plasma concentration-time curve, experimental sample (1) proved to be significantly better than experimental sample (2).
Det viste seg således at ved å dispergere dihydropyridin A forbindelsen med hydroksypropylmetylcellulose for å danne et hurtig-frigjørende fast dispersjonspreparat, ble absorpsjonen av dihydropyridin A forbindelsen i blod bemerkelsesverdig forbedret, og dens biologiske tilgjengelig-het ble meget forsterket. Thus, it was found that by dispersing the dihydropyridine A compound with hydroxypropylmethylcellulose to form a quick-release solid dispersion preparation, the absorption of the dihydropyridine A compound into blood was remarkably improved, and its bioavailability was greatly enhanced.
De følgende eksempler illustrerer oppfinnelsen ytter-ligere. The following examples further illustrate the invention.
Eksempel 1 Example 1
Dihydropyridin A forbindelse (100 g) ble oppløst i vannfri etanol (5 l), og derefter ble hydroksypropylmetylcellulose (500 g) tilsatt for å fremstille en suspensjon. Det organiske oppløsningsmiddel ble derefter avdampet under redusert trykk for å danne et hurtig-frigjørende fast dispersjonspreparat. Dihydropyridine A compound (100 g) was dissolved in anhydrous ethanol (5 L), and then hydroxypropylmethylcellulose (500 g) was added to prepare a suspension. The organic solvent was then evaporated under reduced pressure to form a quick-release solid dispersion formulation.
Eksempel 2 Example 2
Til en suspensjon av dihydropyridin A forbindelse (100 g) og hydroksypropylmetylcellulose (500 g) i vannfri etanol (5 l) ble satt sukrose (9,4 kg), og den resulterende blanding ble omrørt. Derefter ble det organiske oppløsningsmiddel avdampet under redusert trykk for å danne et hurtig-frigjørende: fast dispersjonspreparat. To a suspension of dihydropyridine A compound (100 g) and hydroxypropylmethylcellulose (500 g) in anhydrous ethanol (5 L) was added sucrose (9.4 kg) and the resulting mixture was stirred. Then, the organic solvent was evaporated under reduced pressure to form a quick-release: solid dispersion formulation.
Dette hurtig-frigjørende faste dispersjonspreparat ble omdannet til fine granuler på vanlig måte. This quick-release solid dispersion preparation was converted into fine granules in the usual manner.
Eksempel 3 Example 3
Til en suspensjon av dihydropyridin A forbindelse (100 g) og hydroksypropylmetylcellulose (500 g) i vannfri etanol (5 i.) ble satt laktose (6,87 kg) og lav-substituert hydroksypropylcellulose (1,5 kg), og den resulterende blanding ble omrørt og derefter ble det organiske oppløsningsmiddel avdampet under redusert trykk for å danne et hurtig-frigjørende, fast dispersjonspreparat. To a suspension of dihydropyridine A compound (100 g) and hydroxypropylmethylcellulose (500 g) in anhydrous ethanol (5 l.) was added lactose (6.87 kg) and low-substituted hydroxypropyl cellulose (1.5 kg), and the resulting mixture was stirred and then the organic solvent was evaporated under reduced pressure to form an immediate release solid dispersion preparation.
Efter at det resulterende hurtig-frigjørende, faste dispersjonspreparat var omdannet til granuler på vanlig måte, ble granulene omdannet med magnesiumstearat (30 g) til tabletter på vanlig måte, idet vekten av hver av disse var 180 mg. After the resulting quick-release solid dispersion preparation was converted into granules in the usual manner, the granules were converted with magnesium stearate (30 g) into tablets in the usual manner, the weight of each being 180 mg.
Eksempel 4 Example 4
For hver tablett angitt i eksempel 3 besto belegnings-laget av hydroksypropylmetylcellulose (5,1 mg), titandioksyd (1.6 mg), polyetylenglykol-6000 (0,8 mg), talk (0,4 mg) og jernoksyd-gul (0,1 mg) ble filmbelagt på vanlig måte, for å danne en filmbelagt tablett inneholdende dihydropyridin A forbindelse. For each tablet indicated in Example 3, the coating layer consisted of hydroxypropylmethylcellulose (5.1 mg), titanium dioxide (1.6 mg), polyethylene glycol-6000 (0.8 mg), talc (0.4 mg) and iron oxide yellow (0. 1 mg) was film-coated in the usual manner, to form a film-coated tablet containing dihydropyridine A compound.
Claims (3)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NO843772A NO168627C (en) | 1984-09-20 | 1984-09-20 | PROCEDURE FOR THE PREPARATION OF QUICK-RELEASE DIHYDROPYRIDINE PREPARATION. |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NO843772A NO168627C (en) | 1984-09-20 | 1984-09-20 | PROCEDURE FOR THE PREPARATION OF QUICK-RELEASE DIHYDROPYRIDINE PREPARATION. |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO843772L NO843772L (en) | 1986-03-21 |
| NO168627B true NO168627B (en) | 1991-12-09 |
| NO168627C NO168627C (en) | 1992-03-18 |
Family
ID=19887848
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO843772A NO168627C (en) | 1984-09-20 | 1984-09-20 | PROCEDURE FOR THE PREPARATION OF QUICK-RELEASE DIHYDROPYRIDINE PREPARATION. |
Country Status (1)
| Country | Link |
|---|---|
| NO (1) | NO168627C (en) |
-
1984
- 1984-09-20 NO NO843772A patent/NO168627C/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| NO843772L (en) | 1986-03-21 |
| NO168627C (en) | 1992-03-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| FI83839B (en) | FREQUENCY FRAGMENTATION AND ENHYDROPYRIDINE-A-FRACTION FAST DISPERSION. | |
| FI89005B (en) | PROCEDURE FOR THE FRAMEWORK FOR END DOSAGE WITH ADJUSTMENT PROCEDURE | |
| US20010047000A1 (en) | Partial fatty acid oxidation inhibitors in the treatment of congestive heart failure | |
| US20140357860A1 (en) | Salt of ivabradine with adipic acid | |
| US20020052367A1 (en) | Pharmaceutical compositions containing carvedilol and hydrochlorothiazide | |
| NO344559B1 (en) | Amorphous lercanidipine hydrochloride | |
| EP0371471B1 (en) | Readily absorbable drug formulation of nb-818 | |
| US6475525B1 (en) | Oral preparations containing forskolin derivatives and process for producing pharmaceutical preparations | |
| EP3658122B1 (en) | Pharmaceutical composition comprising sacubitril and valsartan | |
| EP0324982A1 (en) | Inclusion complex of nicardipine or its hydrochloride with beta-cyclodextrin, a process for preparing the same and a sustained release pharmaceutical preparation containing the same | |
| US6887886B2 (en) | Therapeutic compositions comprising excess enantiomer | |
| AU2002351118B2 (en) | Use of (R)-verapamil for the treatment of abnormal increases in gastrointestinal motility | |
| KR101823071B1 (en) | Process for preparing telmisartan-containing tablets | |
| NO168627B (en) | PROCEDURE FOR THE PREPARATION OF QUICK-RELEASE DIHYDROPYRIDINE PREPARATION. | |
| AU2022326581A2 (en) | Osmotic pump controlled-release tablet of insoluble drug and preparation method therefor | |
| KR100708533B1 (en) | Pharmaceutical Composition of Amlodipine Maleate having Enhanced Stability | |
| WO2023128903A1 (en) | Improved manufacturing method for formulations comprising amorphous tolvaptan | |
| NZ209624A (en) | Fast release solid preparation containing dihydropyridine a and hydroxypropylmethyl cellulose | |
| US20140302138A1 (en) | Extended release pharmaceutical compositions containing carbamazepine | |
| WO2024136768A1 (en) | Stable pharmaceutical compositions comprising amorphous tolvaptan | |
| WO2001045710A1 (en) | Pharmaceutical composition containing [1-{[1-(1,3-benzodioxol-5-ylmethyl)-1h-imidazol-5-yl]methyl}-4-(1-naphthyl)-1h-pyrrol-3-yl](4-methyl-1-piperazinyl)methanone |