Pharmaceutical preparation in the form of a foil having an active substance incorporated therein
Abstract
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1 claim: 1 independent, 0 dependent
- 1Revendicare Procedeu pentru condiționaTea unui .medicament sub formă de foița ușor dezagreg abilă în a pă sau solvenți organici, utilizabilă ca inserție, caracterizat prin aceea că substanța activă se amestecă cu un agent plastifiant, ales dintre polimerii de polioxietilenă, polioxipropilenă, poiioxistearați, produse de poliadiție aciisubstituite ale oxidului de etilen, siliconi, glicerina, propilengiicoii sau săpunuri metalice, se dizolvă sau se aduc în suspensie cu 0,01...2% apă, solvenți organici sau un amestec de apă și solvenți organici în soluția sau suspensia obținută și caire reprezintă 48 ... 84 % față de soluția sau suspensia respectivă, înainte de uscare se introduce generatorul de foiță în proporție de 6 . . . 20% ales dintre hidi’oxipropilceluloză, hidroxietileeluloză, meiilhidroxipropiicelulază, metilceluloză sau un amestec al acestora, se adaugă, eventual, materiale de umpluitură în proporție de pînă la 30 %, se omogenizează, iar soluția sau suspensia se trage în foi de grosimea 0/1 ... 2 mm, care se usucă, după uscare avînd grosimea de 0,05 ... 1 mm, după care se divizează în bucăți cie mărimea dorită.
393 paragraphs in 2 sections, as filed
BACKGROUND OF THE INVENTION The present invention relates to a process for conditioning a medicament in the form of a foil that is easily disintegrated in water or organic solvents, for internal or external administration.
Paper sheets coated with active substances for oral administration are known, consisting of water-insoluble cellulose fibers and a water-soluble binder (Patent, Belgium, no. 836363). Sodium carboxymethyl cellulose is preferably used as a water-soluble binder. The active substance is applied 'to the sheet of paper, by dripping the active substance in the form of a solution, pii in its sprinkling on the sheet or by passing the sheet through the solution of the active substance. The batch process, consisting of the separate preparation of the foil and then the application of the active substance to the prepared foil, has the disadvantage that the accuracy of the dosage is not sufficiently accurate, which, in the case of the small doses of the active substance currently administered, is of particular importance. The unspecified doses are generated not only by applying the active substance to the sheet of paper, but also to the preparation and preliminary treatment of the support and the storage of the support material. It was observed, for example, that in the case of the use of the machines for drawing the sheets according to known recipes, a uniform sheet layer does not form and that on drying the sheet is contracted. It is easy to understand that in the case of non-uniform material, neither the reception of the active substance on the sheet can be uniform. In addition, an active substance bound only superficially can detach when handling the sheets, or, for example, the packing operation. At the same time, sodium carboxymethyl cellulose used as a binder can dissolve in the stomach, releasing carboxymethyl cellulose, which incorporates some of the active substance, delaying or preventing the resorption of the drug.
It is also known to administer drugs in the form of ophthalmological insertions, their preparation being done by pressing, injections or by extrusion, at a temperature of 65. . . 204<sup>c</sup>C.
These inserts give up the active substance gradually, for a long time (Patent, RSR, no. 63062).
<sub>25</sub> The present invention provides fast-dissolving inserts and immediately yields the active substance, in that the active substance is mixed with a plasticizing agent, selected from polymers of polyoxy30 ethylene, polyoxypropylene, polyoxystearates, acylsubstituted polyethylene products.
LAW PRICE 4.60
68 336 of ethylene oxide, silicones, giicerine, propylene glycols or metal soaps, dissolve or suspend with 0.01 ... 2% water, organic solvents or a mixture of water and organic solvents, in solution either the suspension obtained, and sometimes represents 48 ... 84% compared to the finished product, before the light is introduced the sheet generator in proportion of 6 ... 20 %, selected from hydroxypropylcellulose, hydroxyethylcellulose, methylhydroxyproipylcellulose, methylcellulose or a mixture thereof, if necessary, fillers in proportion of up to 30% are added, homogenized, and the solution or suspension is drawn in sheets of thickness 0.1 2 mm, do they dry, after drying with a thickness of 0.05 ... 1 mm, after which they are divided into pieces of the desired size.
Further 20 embodiments of the invention are given below.
Example 1. Preparations for 1000 imitates - 0.25 g. . . D-morgestrel - 0.05 g. . . ethinyl estradiol and - 0.84 g. polymers of polyoxyethylene polyoxypropiylene are dissolved under stirring in - 95.00 g. ethyl alcohol and a mixture of powdered powder is introduced into this solution:
- 16.93 g ... hydroxypropyl cellulose and - 16.93. .. cellulose.
The resultant suspension is drawn on a suitable firing apparatus, obtaining an egg layer of 500 m thick which is dried.
A unit contains:
- 0.25 mg. ... Dr. Norgestrel;
- 0.05 mg. .. ethiniioestradiol;
- 0.84 mg. . . polyoxyethylene-polyoxypropylene polymer;
- 16.93 mg ... · hydroxyprcid cellulose;
- 16.93 mg ... cellulose;
35.00 mg.
One unit corresponds to an area of about 3 cm<sup>2</sup>.
The appearance of the sheet: white, similar to paper.
The dry sheet has a thickness of about 170 wal
Example 2. Preparations for 1000 units.
- 1.10 g ... Cremophor EL (acyl-substituted polyethylene oxide product) is dissolved in -152.00 g. .. the water. in this solution are added to the suspension - 0.25 g. D-norgestrel and - 0.05 g. . . ethinyl. In this suspension the following are inserted:
- 22.10 g. . . hydroxypropyl cellulose and - 16.50 g. . . cellulose and possibly homogenate.
The resultant suspension is drawn on a suitable sheet drawing machine, to obtain a layer with a thickness of 500 m », which is then dried.
A unit contains:
- 0.25 mg. . . D-norgestrel;
- 0.05 mg. . . ethinium estradiol;
- 1.10 mg. . . Cremophor EL (acyl-substituted polyethylene product of ethylene oxide;
- 22.10 mg. . . hydroxypropyl cellulose;
- 16.50 mg. . . cellulose;
- 40.00 mg.
One unit corresponds to an area of about 3 cm<sup>2</sup>.
The appearance of the sheet: white, similar to the paper.
The dry sheet has a thickness of about 170 ηιμ.
Example 3. Prepared for 1000 units - 0.03 g. D-norgestrel and - 0.84 g. . . Polyoxyl-40-stearate is dissolved under stirring at -95.00 g. . . ethyl alcohol.
In this solution a powder mixture of:
- 16.93 g. . . hydroxypropikecylose and - 17.20 g. . . cellulose.
The resultant suspension is drawn on a suitable foil drawer, to obtain a layer with a thickness of 500 mr, which is then dried.
A unit contains:
- 0.03 mg. . . D-norgestrel;
—- 0.84 mg. . . poiitoxll - 40 - stearate;
- 16.93 mg. . . hydroxypropyl cellulose;
- 17.20 mg. . . cellulose.
35.00 mg.
One unit corresponds to an area of about 3 cm<sup>2</sup>.
The appearance of the sheet: white, similar to paper.
The light sheet has a thickness of about 170 m | A
Example 4. Prepared for 1000 units - 1.10 g., Polyoxyethylene polyoxypropylene polymers are dissolved in - 152.00 g. . . demineralized water.
In this solution the following are suspended:
- 0.03 g. . Micronized D-norgestrel and eventually homogenized.
In this suspension the following are inserted:
- 22.10 g. hydroxypropyl cellulose and - 16.77 g ... cellulose.
The resultant suspension is drawn on a suitable sheet puller to obtain a layer with a thickness of 500 mr, which is then dried.
A unit contains ·:
- 0.03 mg. .. D-norgestrei;
- 1.10 mg. polyoxyethylene-polyoxypropylene polymer;
- 22.10 mg. . . hydroxypropyl cellulose;
— 16<sub>r</sub>77 mg. . . cellulose.
40.00 mg.
A unit corresponds to an area of about 3 cm<sup>2</sup>.
The appearance of the sheet: white, similar to paper.
The dry sheet has a thickness of about 170 myt
Example 5. Preparation for 1000 units - 0.025 g. . . fluocOrtotcmtrimetiiiace-tiat and - 0.183 g. .. glycerin dissolves in - 30,000 g. . . eltilie alcohol.
7,292 g are introduced into this solution. . . hidiroxipropilceiuiloză.
The solution obtained is drawn on a suitable sheet drawing machine, to obtain a layer with a thickness of 500 ml<sup>1</sup>, which is then dried.
A unit contains:
- 0.025 mg. . . fluocortolone-trimethylacetate;
- 0.183 mg. . . glycerine;
- 7.292 mg. hydroxypropyl cellulose, 7T5Wmg ^
A unit corresponds to a surface of 1 man<sup>2</sup>.
The appearance of the sheet: transparent.
The dry sheet has a thickness of about 70 sqm.
The foil is suitable for local application.
Example 6. Prepared for. 1000 units - 10.00 g. 7-chloro-2-meIlyliatmino-5-phenyl-3H-1, 4-benzoidinzepin-4-oxide and - 0.84 g. polymers of polyoxyethyleneapolixypropylene are dissolved in - 95.00 g. . . ethyl alcohol.
In this solution, a powder mixture of:
- 16.93 g. . . hydrosiproprcululose and - 7.23 g. . . cellulose.
The resultant suspension is pulled on a suitable foil drawer, to obtain a layer with a thickness of 500 im<sup>1</sup>, which is then dried.
A unit contains:
- 10.00 mg. . . 7-chloro-2-methylamino-5-phenyl-3H-1,4-benzodiazepine-4-oxide;
- 0.84 mg. . . polymers of polyoxyethylene-polyoxypropylene;
- 16.93 mg, .. hydroxypropyl cellulose;
—- 7.23 mg ... cellulose.
35.00 mg.
One unit corresponds to an area of about 3 cm<sup>2</sup>.
The appearance of the sheet: yellow, similar to the hoof.
The dry sheet has a thickness of about 170 sq m.
Example 7, Preparation for 1000 units - 1.00 g ... norethistorone acetate;
- · 0.03 g. ethinyl oestradiol and - 0.84 g. . . polymers of poly-oxyethylene-dihydroxypropylene are dissolved in:
- 95.00 g. . . ethyl alcohol.
In this solution a powder mixture of - 16.93 g ... hydroxypropyl cellulose and - 16.20 g ... cellulose is introduced.
The resultant suspension is drawn on a suitable foil drawer, to obtain a layer with a thickness of 500 mr, which is then dried.
A unit contains:
- 1.00 mg. . . non-rethisterone acetate;
- 0.03 mg. · · Ethinylcestraldiol;
- 0.84 mg. . . polyoxyethylene polyoxypropylene;
- 16.93 mg ... hydroxypro-pilcellulose;
- 16.20 mg_. . . cellulose.
35.00 mg.
One unit corresponds to an area of about 3 cm<sup>2</sup>.
The appearance of the sheet: white, like portraits,
The dry sheet has a thickness of about 170 stems
Example 8. Prepared for 1000 units - 1.00 g. norethisterone acetate;
- 0.03 g. etinb this radio! and - 0.84 g. . . propylene glycol is dissolved in a mixture of - 101.60 g. . . methylene chloride and - 26.40 g. . . ethyl alcohol.
In this solution a powder mixture of:
- 8.47 g ... hydroxypropyl cellulose;
- 8.47 g. . . hydroxyethyl cellulose and - 16.19 g. .. cellulose.
The resulting suspension is drawn onto a suitable sheet of steel to obtain a layer with a thickness of 500 mu, which is then dried.
A unit contains:
- 1.00 mg. . . norethisterone acetate;
- 0.03 mg. . . and Illinoestradiol;
- 0.84 mg. . . pro pSi-etn him col;
- 8.47 mg. . . hydroxypropyl cellulose;
- 8.47 (mg. Hydroxyethyl cellulose;
-16.19 mg. . . cellulose.
35.00 mg.
One unit corresponds to a surface of 3 cm<sup>2</sup>.
The appearance of the sheet: abe, similar to the paper.
The dry sheet has a thickness of about 170 mto
Example 9. Preparation, per 1000 units - 1.00 g. . . nonethyletherone acetate;
- 0.03 g. . . and / iniloesitradyl and - 0.84 g,. . polyoxyethylene-polyoxypropylene polymers are dissolved in a mixture of:
- 101.60 g ... mild methyl chloride and • - 25.40 g. . . ethyl alcohol.
In this solution a powder mixture of:
- 16.93 g. . . hydroxylcellulose and - 16.20 g. starch.
The resulting suspension is drawn on a suitable sheet puller, to obtain an egg layer of 500 m thick, and then dried.
A unit contains:
- 1.00 mg. . . norethisterone acetate;
- 0.03 mg. . . etiniloestraidiol;
- 0.84 mg. . . polyoxyethylene-polyoxyprcylene polymer;
- 16.93 mg. . . hydroxyethyl cellulose;
- 16.20 mg. . . starch.
35.00 mg.
One unit corresponds to an area of about 3 cm<sup>2</sup>.
The appearance of the sheet: aib, similar to paper.
The dry sheet has a thickness of about 170 mi! -L
Example 10. Preparation for 1000 units - 1.00 g. . . norethisterone acetate;
- 0.03 g. . . ethinyl eistradiol and - 0.84 g. .. polyoxyl-40-stearate is dissolved in - 95.00 g. . . ethyl alcohol.
In this solution a powder mixture of:
- 16.93 g. . . hidiOxypropyl cellulose;
- 8.10 g. . . lactose;
- 8.10 g. ,. corn starch.
The resultant suspension is drawn on a so-called "foil" sheet, to obtain a layer with a thickness of 500 mr, and then it dries.
A unit contains:
<td>- 1.00 mg.</td><td>. . norethystero acetate</td>
<td>N / A ;</td><td></td>
<td>- 0.03 mg.</td><td>. . ethynyloestradyc and</td>
<td>- 0.84 mg.</td><td>. . poliiOxil-40-stearate;</td>
<td>- 16.93 mg.</td><td>. . Hydroxypropylcellulose;</td>
<td>- 8.10 mg.</td><td>. . corn starch.</td>
35.00 mg.
One unit corresponds to an area of about 3 cm.<sup>2</sup>.
The appearance of the sheet: white, similar to paper.
The dry sheet has a thickness of about
170 m (u.
Example 11. Prepared for 1000 units - 1.00 g. norethisterone (17-ethynyl 19-nor-testosterone);
- 0.03 g. . . ethinyl estradiol.ol and - 0.22 g. . . polyoxyethylene-pdioxypropylene polymers are dissolved in a mixture of:
- 84.76 g ... ethyl alcohol and - 4.00 g. . . the water. In this solution a powder mixture of:
- 16.00 g. . . hydroxypropyl cellulose and - 16.00 g. . . cellulose and possibly homogenized ·.
The resulting suspension is drawn on a suitable sheet-firing device, to obtain a layer with a thickness of 800 mc, then the cups are dried.
A unit contains:
- 1.00 mg. . . norethisterone (17-ethynyl-19-nor-tesitosterone);
- 0.03 mg. . . ethinyl estnadiol;
- 0.22 mg. . . polyoxyethylene-poly Qxiprapilene polymer;
- 16.00 mg. . . hydroxypropyl cellulose;
- 16.00 mg. . . cellulose.
33.25 img.
The surface of a unit about 3 cm<sup>2</sup>.
The appearance of the sheet: white, similar to paper.
The dry sheet has a thickness of about 230 m3.
Example 12. Preparation for 1000 zenith - 4.0 g. . . glisoxepid *) in midronized form dissolves in:
- 0.9 g. . . polioxyI-40-stearate and is suspended in:
- 152.0 g. . . water and eventually homogenize.
In this suspension the following are inserted:
- 15.0 g. hydroxyethyl cellulose and - 15.1 g. calcium carbonate.
The resultant suspension is drawn on a suitable sheet puller, to obtain a layer, with a thickness of 500 cubic meters, which is then dried.
A unit contains:
- 4.00 mg. . . glisoxepid *);
- 0.90 mg. . . polyoxyl-40-stearate;
- 15.00 mg. . . hydroxyethyl cellulose;
- 15.10 mg. . . calcium carbonate.
35.00 mg.
One unit corresponds to an area of about 3 cm<sup>2</sup>.
The appearance of the sheet: white, paper-like,
The dry sheet has a thickness of about 170 nites <sup>c</sup>) 4- and 4- IE- (3-methyl-isoxazol-3-carboxamido)] -ethyl) -benzer- ,;<sup>,</sup>j.Koni) -lp.-hexamethyl-semicafoacicl
Example 13. Preparation for 1000 units - 0.030 g. . . D-norgestrel is dissolved in:
- 40,000 g. . . methylene chloride and - 55,000 g. . . ethanol.
This solution introduces:
- 0.840 g. . . silicone oil;
- 6,930 g. . . methylcellulose and - 16,000 g. . . poly-N-vinylpyrrolidone and - 17,200 g. . . starch and possibly homogenize.
The resultant suspension is drawn on a suitable foil drawer to ob * 883 «y
it holds a layer with a thickness of 500 im<sup>1</sup>, which is then dried.
A unit contains:
- 0.030 mg. . . D-norgestrel;
- 0.840 mg. . . silicone oil;
- 6,930 mg. . . methicellulose;
- 10,000 mg. . . poly-N-vinylpyrrolidone;
- 17,000 mg. . . starch.
35,000 mg.
One unit corresponds to an area of about 3 cm<sup>2</sup>.
The appearance of the sheet: white, similar to paper.
The dry sheet has a thickness of about 170 m +.
Example 14. Prepared for 1000 units - 0.84 g. . . polyoxyethylene-polyoxypropene polymers are dissolved under stirring in:
- 95.00 g. . . ethyl alcohol.
In this wife a mixture of dust is introduced:
- 17.08 g. . . hydroxypropyl cellulose and - 17.08 g ... cellulose.
The resultant suspension is drawn on a foil drawer, to obtain an egg layer the thickness of 500 nr<sup>!</sup>, which then dries.
A unit contains:
- 0.84 mg. . . polymers of polyoxyethylene-polyoxypropylene;
- 17.08 mg. . . hydroxy oxide pi: cellulose; -17.08 ηζχ. . cellulose.
35.00 mg.
Example 15. Prepared for 1000 omits - 0.04 g. . . old;
- 0.04 g. . . essence of milk cream And - 0.40 g. . . polyoxyethylene-polyoxypropylene polymers are dissolved in a mixture of:
- 79.00 g. . . ethyl alcohol and - 4.00 g ... water.
This solution introduces:
- 30.00 g. . . iron fumarate - (11);
- 15.00 g ... hydroxypropyl cellulose;
- 5.52 ig. . . cocoa and - 4.00 g. . . cellulose and eventually become cgenogenized.
The resulting suspension is drawn on a suitable foil drawing device, to obtain a layer with a thickness of 0.5 ms, which is then dried.
A unit contains:
- 30.00 mg. . . iron fumarate - (II);
- 15.00 mg. . . hydroxypsx> pilce> l'ulose;
- 4.00 mg. . . cellulose;
- 0.40 mg. . . polyoxyethylene-pallioxyproipylene polymer;
- 5.52 mg. . . cocoa;
- 0.04 mg. . . sugar;
- 0.04 mg. . . essence of milk cream.
IO
55.00 mg. . . weight / unit.
One unit corresponds to an area of about 3 cm<sup>2</sup>.
Leaf appearance: light reddish mairo.
Example 16. Sheets for intravaginal application
The foil is prepared as described in Example 11.
A unit contains:
- 100.0 mg. . . 5-morpholinomethyl - 3 - (5-nitro-1-melyl-2-imidazoldl) -methylenamino-2-oxazolidinone. HCl;
- 8.4 mg. . . Cremofor El;
- 72.4 mg. . , cellulose;
- 350.0 mg. . . w! unit.
One unit corresponds to an area of about 8 X 4 cm.
The foil (a unit) is wrapped either on a commercial or single tampon, in a thin tube.
Example 17. Two-phase preparation
Part 1: 21 units with active substance.
Part 2: 7 units without active substance.
Prepared for 3000 units, part 1: 0.75 g. D-norgestrel;
- 0.15 g. . . ethinylotestradicl and - 0.54 g. polyoxyethylene-polyoxypropylene polymers are dissolved in:
- 237.0 g. . . ethyl alcohol and - 12.00 g. . . the water.
This solution introduces:
- 44.28 g. . . hydroxypropyl cellulose and - 44.28 g. cellulose and eventually homogenized.
Prepared for 1000 units, part 2 - 0.18 g. . . polyoxyethylene-polyoxypropylene polymers are dissolved in a mixture of:
- 79.00 g. . . ethyl alcohol and - 4.00 g. .. the water.
This solution introduces:
- 14.91 g. hydroxypropyl cellulose and - 14.91 g. . . cellulose and possibly homogenized.
The resultant suspension is drawn on a suitable sheet puller, provided with a special two-chamber scraper, (width of a chamber 1 = 54 mm; = 18 mm), to obtain a layer with a thickness of 0.5 mm which then dry. By properly dividing them into units of 18 χ 18 mm, for example, by drilling, three units with the active substance and one unit without the active substance can be detached from the width of the sheet. From the sheet of paper you can get any number of sections, of three units with active substance and one unit without active substance.
A unit contains:
Part 1
Part a (with active substance) 2 ~ u, the active substance
0.25 mg D-noirgestirel -0.05 mg ethinyl estradiol
14.76 mg hSidiroixipropiiloeiuArea 14.91 mg 14.76 mg, cellulose 14.91 mg
0.18 mg polyoxyethylene polymer aHpolioxypropylene 14.91 mg
30.00 rpg weight per unit 30.00 mg
Surface area: about 2 cm<sup>2</sup>.
Appearance: «white.
Example 18. Three-phase preparation (I two active substance concentrations)
Part 1: 11 units with 0.05 mg D- 20 norgestirel;
0.05 mg ethinyl estradiol.
Square 2: 10 units with 0.125 mg
G-niorgiestirel;
0.05 mg ethinyl estradiol. <sub>25</sub>
Part 3: 7 units without active substance.
Prepared for 1100 units, part 1 - 0.055 g., D-norgesteel;
- 0.055 g. .. ethinyl estradiol and<sub>3Q</sub> - 0.198 g. polyoxyethylene-polyoxypropylene polymers are dissolved in a mixture of:
- 86,900 g. .. «ethyl alcohol and - 4,400 g. .. "the water.<sub>35</sub>
This solution introduces:
- 16,346 g ... hydroxyipi'ppilceiiulase and - 16,346 g. cellulose and eventually homogenized.
.12
Prepared for 1000 units, part 2:
- 0.125 g. D-norgestrel;
- 0.050 g ... polyoxyethylene-polyoxypropylene polymers are dissolved in a mixture of:
- 79,600 g. . . ethyl alcohol and - 4,000 g. . . the water.
In «this solution is introduced:
- 14,823 g. . . ΙιΐύΐΌχΐρΐΌρϋοθΙηΙοζβ and - 14,823 g. . . cellulose and possibly homogenized.
Prepared for 700 units, part 3:
- 0.189 g. polymers of polyoxyethylene-poilioxipro.pilene are dissolved in a mixture of:
- 82,950 g. .. ethyl alcohol and - - 4,200 g. . . "the water.
in this mixture the following are obtained:
- 15.656 g,. . hydroxypropyl cellulose and -— 15,656 g. . . cellulose and possibly homogenized;
The resultant suspension is drawn on a suitable foil drawer, provided with a special scraper with chambers (the width of the chambers 18 mm), to «get a layer, does it« then dry. By proper division, for example, by punching, units of width 18 X 18 mm, for part 1, 18 χ 19.8 mm, for part 2, and 18 X 28 mm, for part can be detached 3, with different contents of active substance. From the sheet of paper you can detach prep «show with 11 units part 1, 10 units part 2 and 7« units part 3,
A unit contains:
<td>Part 1</td><td>Paitca the 2nd</td><td>Part 3</td><td>Content of substances</td>
<td>0.050 mg 0.050 mg 0.180 mg 14,860 mg 14,860 mg</td><td>0.125 mg 0.050 mg 0.180 mg 14,823 mg 14,822 mg</td><td>0.270 mg 22.366 mg 22,364 «mg</td><td>D-norgestrel ethinyloiestradiol polymers of polyoxyethylenepalioxy propylene yeast oxypropyl cellulose celuljoză</td>
<td>30,000 mg about 3 cm<sup>of</sup>white</td><td>30,000 mg about 3.5 "cm<sup>5</sup>(white</td><td>45,000 mg about 5 cm<sup>2</sup>white</td><td>weight on some: atheists surface per unit appearance</td>
Example 19. Three-phase preparation 40
Part 1: 11 units with 0.05 mg Dnorgesirel;
0.05 mg ethinyl estradiol.
Part 2: 10 units with 0.125 mg
D-norgestrel; 45
0.05 mg ethinyl estradiol.
Part 3: 7 units with 50.00 mg iron fumarate - (II).
Ready for 1100 units, part 1:
- 0.066 g. . . yellow dye, food, no. 2 (Tartrazine; E 162) dissolves in:
- 4,400 g in - 86,900 g In this - 0.055 g - 0.055 g - 0.198 g. . water and then enter. . ethyl alcohol.
solution dissolves:
. . D-norgestrel;
. . ethinyl estradiol and. . polymers of polyoxyethylenesΗ
<td>—- 0.042 g.</td><td>. . saccharin;</td>
<td>- 0.042 g. .</td><td>. essence of dc cream -</td>
<td>you and</td><td></td>
<td>- - 0.406 g. .</td><td>. polymers of polyoxyethyl-</td>
n-p oil oxypropylene.
This solution introduces:
<td>- 16,313 g. .</td><td>. hydroxypropyl cellulose and</td>
<td>- 16,313 g. . ,</td><td>. cellulose and possibly se</td>
<td>homogenized.</td><td></td>
<td colspan="2">Ready for 1000 units, the part</td>
<td>2nd:</td><td></td>
<td>- 0.065 g. . .</td><td>, orange color, aii-</td>
<td>mentar no. 2</td><td>(Sunset Yelow; E 110) if</td>
<td>dissolve by:</td><td></td>
<td>- 4,000 g. . .</td><td>water and then enter</td>
<td>in the :</td><td></td>
<td>- 79,000 g. .</td><td>. ethyl alcohol.</td>
<td>in this variety</td><td>dissolution is dissolved:</td>
<td>- 0.125 g ...</td><td>. D-norgerstrel;</td>
<td>- 0.050 g. .</td><td>. ethinyl estradiol and</td>
<td>- 0.180 g. . .</td><td>polymers of polyoxyethyl-</td>
n-poldioxypropylene dissolves in an a-
<td colspan="3">meisiietc of<sup>:</sup> :</td>
<td>- 55,300 g.</td><td>. . ethyl alcohol and</td><td></td>
<td>- ~ 2,800 g.</td><td>. . the water.</td><td></td>
<td>in that</td><td>solution is introduced:</td><td></td>
<td>- 35,000 g.</td><td colspan="2">. . iron fumarate - (II);</td>
<td>- 17,500 g.</td><td>. . hydroxyprcpiloelulose;</td><td></td>
<td>- 5,950 g.</td><td>. . cocoa and</td><td></td>
<td>- 4,060 g.</td><td>. . cellulose and possibly</td><td>it</td>
<td>omegenizţează</td><td></td><td></td>
<td colspan="2">The resulting suspension is drawn on one</td><td>a-</td>
<td>back stop</td><td>suitable sheets, provided</td><td>with</td>
Na-polioxiproţpil | ene.
This solution introduces:
- 14,790 g ... h Hydroxypropyl cellulose and - 14,790 g. . . cellulose and possibly homogenized.
Prepared for 700 units, part 3:
a special scraper with three chambers (the width of a chamber 18 mm), to obtain a strait, which is then dried. By proper division, for example, by drilling, in units of 18 X 18 mm, for part 1, 18 X 19.8 mm for part 2 and 18 X 28 mm, for part 3, they can be detached from the width of the unit sheet with different active substance contents. From the sheet of paper can be prepared preparations with 11 units part 1, 10 units part 2 and 7 units part 3.
A unit contains :
<td>The part at</td><td colspan="2">Part 2</td><td>Part 3</td><td>Content of substances</td>
<td>0.050 mg</td><td> 0,125</td><td>mg</td><td> —</td><td>D-norgestrel</td>
<td>0.050 m, g</td><td> 0,050</td><td>mg</td><td> —</td><td>e.ti njilloestradiol</td>
<td> —</td><td> —</td><td></td><td>50,000 mg</td><td>iron fumarate - (II) pallioxyethylene polymer-</td>
<td>0.180 mg</td><td> 0,180</td><td>mg</td><td>0.580 mg</td><td>poliioxipropilenă</td>
<td>0.060 mg</td><td> —</td><td></td><td> ’—</td><td>yellow food coloring no. 2 orange food coloring</td>
<td> —</td><td> 0,065</td><td>mg</td><td> —</td><td>no. 2</td>
<td>14,830 mg</td><td> 14,790</td><td>mg</td><td>25,000 mg</td><td>hydr oxiprcpilcclul ozon</td>
<td>14,830 mg</td><td> 14,790</td><td>mg</td><td>5,800 mg</td><td>cellulose</td>
<td> —</td><td> —</td><td></td><td>8.50 | 0 mg</td><td>cajcaio '</td>
<td> —</td><td></td><td></td><td>0.060 mg</td><td>saccharine</td>
<td> —</td><td></td><td></td><td>0.060 mg</td><td>essence of milk cream</td>
<td>30.00 mg</td><td> 30,000</td><td>mg</td><td>90,000 mg</td><td rowspan="2">weight / unit</td>
<td>is about 3 crX</td><td>about 3</td><td>, 5 cm<sup>2</sup></td><td>about 5 cm<sup>2</sup></td>
<td>and galbsjn</td><td colspan="2">portoeiaiiiu</td><td>mato</td><td>surface / units</td>
Example 20. Prepared for 1000 units
<td>0.15 g. ,</td><td>,. D-norgestrel;</td><td></td>
<td>0.03 g.</td><td>. . ethinyl estradiol;</td><td></td>
<td>0.84 g.</td><td>. . polymers of polyoxyethylene-</td><td> 35</td>
polyoxypropylene dissolves under stirring in:
...... 95.00 g ... ethyl alcohol.
In this solution a powder mixture of:
- 16.99 g. . . hydroxypropyl cellulose and - 16.99 g. . . cellulose.
The resultant suspension is drawn on a suitable foil drawer, to obtain a layer with a thickness of 500 nv which is then dried.
A unit contains:
--- 0.15 mg. . . D-norgesirel;
- 0.03 mg. . . ctinylcestradiol;
- 0.84 mg. . . polymers they polyoxyethylene-polyoxycopile;
- 16.99 mg. . . hydroxypropylsululose;
- 16.99 mg,. . cellulose.
35.00 mg.
One unit corresponds to an area of about 3 cm<sup>2</sup>.
The appearance of the leaf has a, like the lashing of lime.
The dry sheet has a thickness of about 170 m.
The method of preparing the inserts follows: the sheet generator hydroxyethyl alcohol of water soluble cellulose, such as hydroxyethyl cellulose and methydroxypropyl ketosis, as well as methylcellulose, is introduced into the suspension or solution obtained by mixing the active solution with the plasticizing agent with water, organic solvents or a mixture of water, and a mixture of water and mixture. obtained, if necessary, fill materials are added, then the solution or suspension is drawn in sheets of thickness 0,1 ... 2 mm which dries, after drying with a thickness of 0.05 ... 1 mm, after which it is divided into pieces of the desired thickness.
For a better understanding of the invention, the following are also shown:
As can be seen from the examples above, the process according to the invention can be used to prepare strips of sheet ir, which, along the width of the strip, are located next to units in the tub, incorporating different active substances and / or different concentrations of the active substances. With the help of a special scraper, consisting of two or more chambers, layers can be drawn from different solutions, respectively, suspensions, resulting in a coherent layer, without the layers being mixed. The width and thickness of each layer is individually adjustable for each room. Optionally, the different zones (bands) with active substances, respectively, with different concentrations of different active substances, can be made visible or different co-adjacent. By drying the resulting layer, a foil is obtained from which, by proper division, for example, by drilling, units with different active substances and / or or different concentrations of the active substance are obtained. The foil with different active substances and / or with different concentrations of active substance are necessary to obtain preparations! with several phases, for example. pen16 to obtain contraceptive preparations. By the possibility of separating the different incompatible substances, in a single sheet unit, the stability of the respective active substances is improved. For intra-vaginal application, the sheets can be wrapped, for example, on a commonly used commercial pad.
The sheet generator can be filled with fillers and active substances, as well as small quantities of an insulating agent.
Suitable insulating agents include, but are not limited to, the polyoxyethylene-polyoxypeptyl polymers (Plu-ronic F 68), polyoxystearates, the acyl-substituted polyadiene products of ethylene oxide, for example (Cremophoir El); silicones and insulating silicone, glycerin, pcopiLanglycol and metal soaps.
Ga filling materials can be used. for example, cellulose, sugars, such as, for example, lactose ·, dextrose, sucrose, etc. ; starches, polyvalent alcohols, such as mannit; then calcium carbonate, talc and soluble dyes or pigments. The filling materials can be replaced partially or totally with active substances. If the fillers, respectively, soluble active substances are used, then a transparent foil is obtained, and if the fillers, respectively, the insoluble active substances are used, then a white or colored foil, similar to the paper, is obtained.
According to the invention, all the active substances used in human and veterinary medicine can be incorporated. For internal use, oral administration may be considered in particular. By external use we mean, in particular, the local administrations, on the skin and body cavities, such as the nose, ear, vagina, etc. As active substances are mentioned as examples: gestagens, estrogens, mixtures of gestagens and oestragens, transchilizers, antidiabetic drugs. sulfonamides. antibiotics, typhlogistic drugs, for example, corticosteroids, etc.
The active drug substance can be present in the support material, either in dissolved form or in uniform suspension. The amount of active substance can be about 0 ... 60%. As a dose (unit), surfaces containing the active substance are cut or perforated, as are tablets, dragees, aliphs, suppositories, etc. In the cut surfaces, the active substance can be present in different quantities, ranging from 1 g to 0.5 g, being possible both lower and higher doses than the mentioned limiflelc.
68336
Naturally, carriers without active substance can also be prepared.
In the preparation of medicines in sheet form, according to the invention, the sheet generator can be present in solution, 5 respectively, in suspension, in quantities of about 6. . . 20% by weight, the filling material in quantities of about 0. . .
% and the separation agent preferably in an amount of about 0.01. . . 2% by weight.
The solvent or suspension medium represents about 48 in the mixture. . . 84% (v / v) and consists of water and / or one or more organic solvents. As soil-<sub>15 </sub>organic incomes may be considered acceptable solvents from a physiological point of view or solvents which, upon drying, can be removed up to a physiologically insignificant residue. <sub>2θ </sub>Such solvents are, for example, ethyl alcohol, isopropanol, methylene chloride, etc. and their mixtures. Preferably water and ethyl alcohol are used, respectively water and ethanol blends.
The thickness of the resulting layers represents about 0, 1 to 2 mm and that of the dry sheet about 0.05 to 1 preferably 0.7 to 0.3 mm. <sub>3C</sub>
The process according to the invention has the following advantages:
- the active substance is found uniformly and evenly in the carrier of the active substance;
- the administrative dose may be slightly variable, varying the concentration of the active substance in the support, the thickness and the surface of the sheet.
- the process is simple to perform and has a single phase;
- the obtained products are stable over time.
Contents2
44 members in 27 offices
Priority claims2
| Document | Office | Kind | Date |
|---|---|---|---|
| 2432925 | Germany | A | |
| 2449865 | Germany | A |
Members44
| Document | Office | Kind | |
|---|---|---|---|
| BE831024A | Belgium | A | |
| IE42604L | Ireland | L | |
| DK295075A | Denmark | A | |
| FI751801A | Finland | A | |
| NO752416L | Norway | L | |
| NL7507785A | Netherlands (Kingdom of the) | A | |
| SE7507659L | Sweden | L | |
| DE2432925A1 | Germany | A1 | |
| FR2276811A1 | France | A1 | |
| JPS5129218A | Japan | A | |
| DE2449865A1 | Germany | A1 | |
| ZA754305B | South Africa | B | |
| DD122196A5 | German Democratic Republic (until 1990) | A5 | |
| AU8252775A | Australia | A | |
| ES439159A1 | Spain | A1 | |
| IN142428B | India | B | |
| EG11756A | Egypt | A | |
| ATA513275A | Austria | A | |
| CS181182B2 | Czechoslovakia (until 1993) | B2 | |
| GB1510999A | United Kingdom | A | |
| IL47573A | Israel | A | |
| AT346492B | Austria | B | |
| US4136145A | United States of America | A | |
| US4136162A | United States of America | A | |
| HU173016B | Hungary | B | |
| PL101842B1 | Poland | B1 | |
| US4152159A | United States of America | A | |
| CA1067407A | Canada | A | |
| FR2276811B1 | France | B1 | |
| SE413285B | Sweden | B | |
| RO68836AThis record | Romania | A | |
| IE42604B1 | Ireland | B1 | |
| DE2432925B2 | Germany | B2 | |
| DE2449865B2 | Germany | B2 | |
| DK143221B | Denmark | B | |
| FI60354B | Finland | B | |
| CH625704A5 | Switzerland | A5 | |
| DK143221C | Denmark | C | |
| FI60354C | Finland | C | |
| JPS6028810B2 | Japan | B2 | |
| DE2432925C3 | Germany | C3 | |
| PH18973A | Philippines | A | |
| NL186294B | Netherlands (Kingdom of the) | B | |
| NL186294C | Netherlands (Kingdom of the) | C |
Numbers
- Application
- 7582701
Titles3
- French
- PROCEDE POUR CONDITIONNEMENT D'UN MEDICAMENT EN FORME DE FEUILLE MINCE FACILEMENT DE DECOMPOSEE DANS L'EAU OU SOLVANTS ORGANIQUES
- Romanian
- PROCEDEU PENTRU CONDITIONAREA UNUI MEDICAMENT SUB FORMA DE FOITA USORDEZAGREABILA IN APA SAU SOLVENTI ORGANICI
- English
- PROCEDURE FOR CONDITIONING A MEDICINE IN THE FORM OF SUGGESTABLE FOOTAGE IN WATER OR ORGANIC SOLVENTS
Classification
- CPC, 1
- A61K9/7007
- IPC, 2
- A61K9 70
- A61K31 57