IES65615B2 - Pharmaceutical processing - Google Patents
Pharmaceutical processingInfo
- Publication number
- IES65615B2 IES65615B2 IES950586A IES65615B2 IE S65615 B2 IES65615 B2 IE S65615B2 IE S950586 A IES950586 A IE S950586A IE S65615 B2 IES65615 B2 IE S65615B2
- Authority
- IE
- Ireland
- Prior art keywords
- tablets
- active pharmaceutical
- pharmaceutical ingredient
- direct compression
- lubricant
- Prior art date
Links
- 238000007907 direct compression Methods 0.000 claims abstract description 17
- 238000002156 mixing Methods 0.000 claims abstract description 16
- 239000000314 lubricant Substances 0.000 claims abstract description 14
- 239000008186 active pharmaceutical agent Substances 0.000 claims abstract description 13
- 239000000203 mixture Substances 0.000 claims abstract description 13
- 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 abstract description 11
- 239000008101 lactose Substances 0.000 claims abstract description 11
- 239000003112 inhibitor Substances 0.000 claims abstract description 9
- 230000003993 interaction Effects 0.000 claims abstract description 5
- 238000000034 method Methods 0.000 claims description 14
- 239000004615 ingredient Substances 0.000 claims description 9
- 229920002472 Starch Polymers 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 239000008107 starch Substances 0.000 claims description 5
- 235000019698 starch Nutrition 0.000 claims description 5
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 abstract description 14
- 235000019359 magnesium stearate Nutrition 0.000 abstract description 7
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 abstract description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 abstract description 3
- 229940069328 povidone Drugs 0.000 abstract description 3
- ZKNJEOBYOLUGKJ-ALCCZGGFSA-N (z)-2-propylpent-2-enoic acid Chemical compound CCC\C(C(O)=O)=C\CC ZKNJEOBYOLUGKJ-ALCCZGGFSA-N 0.000 abstract description 2
- 229960002016 oxybutynin chloride Drugs 0.000 abstract description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 abstract description 2
- 238000003556 assay Methods 0.000 description 5
- 238000009472 formulation Methods 0.000 description 4
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 3
- 239000008108 microcrystalline cellulose Substances 0.000 description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 description 3
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- MAEIEVLCKWDQJH-UHFFFAOYSA-N bumetanide Chemical compound CCCCNC1=CC(C(O)=O)=CC(S(N)(=O)=O)=C1OC1=CC=CC=C1 MAEIEVLCKWDQJH-UHFFFAOYSA-N 0.000 description 2
- 229960004064 bumetanide Drugs 0.000 description 2
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical class CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 235000019759 Maize starch Nutrition 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 239000004141 Sodium laurylsulphate Substances 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- FETSQPAGYOVAQU-UHFFFAOYSA-N glyceryl palmitostearate Chemical compound OCC(O)CO.CCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O FETSQPAGYOVAQU-UHFFFAOYSA-N 0.000 description 1
- 229940046813 glyceryl palmitostearate Drugs 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
- NDDAHWYSQHTHNT-UHFFFAOYSA-N indapamide Chemical compound CC1CC2=CC=CC=C2N1NC(=O)C1=CC=C(Cl)C(S(N)(=O)=O)=C1 NDDAHWYSQHTHNT-UHFFFAOYSA-N 0.000 description 1
- 229960004569 indapamide Drugs 0.000 description 1
- -1 light mineral oil Substances 0.000 description 1
- 229940059904 light mineral oil Drugs 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000005550 wet granulation Methods 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Tablets are produced by directly compressing a mixture formed by dry blending an active pharmaceutical agent such as oxybutynin chloride, direct compression lactose, a lubricant such as magnesium stearate and an inhibitor such as a cross povidone based product. The inhibitor prevents interaction between the direct compression lactose and the active pharmaceutical ingredient.
Description
Pharmaceutical Processing The invention relates to a method for producing tablets of an active pharmaceutical ingredient.
There are two main techniques for formulating tablets of pharmaceutically active compounds - wet granulation and direct compression.
Direct compression is preferred for active ingredients which react adversely with aqueous media. However, there are problems in producing satisfactory tablets by direct compression techniques. These include blending/unblending, poor flow characteristics, poor compressibility of tablet ingredients and low colour potential.
This invention is therefore directed towards providing an improved method for producing tablets of an active pharmaceutical ingredient.
According to the invention there is provided a method for producing tablets of an active pharmaceutical ingredient comprising the steps of: mixing the active pharmaceutical ingredient, a lubricant, direct compression lactose, and an amount of an inhibitor to substantially prevent interaction between the direct compression lactose and the active pharmaceutical ingredient; and * directly compressing the mixture thus formed to form * tablets. - 2 In one embodiment of the invention, the inhibitor is a starch product or a derivative of a starch product such as carboxymethyl starch.
In another embodiment of the invention, the inhibitor is a cross-povidone based product.
Preferably the formulation includes a lubricant and the method includes the step of mixing the ingredients except the lubricant; subsequently adding the lubricant; and further mixing the ingredients.
Any suitable lubricant may be used such as stearic acid salts e.g. magnesium, calcium or zinc stearate. Other suitable lubricants include glyceryl monostearate, glyceryl palmitostearate, hydrogenated castor oil, hydrogenated vegetable oil, light mineral oil, mineral oil, polyethylene glycol, sodium benzoate, sodium lauryl sulphate, sodium stearyl fumarate, stearic acid and talc.
Most preferably mixing is performed using a dry blending technique.
The invention also provides tablets of an active pharmaceutical ingredient whenever prepared by a method according to the invention.
The invention will be more clearly understood from the following description thereof given by way of example only.
We have found that if tablets are produced by a direct compression technique using a lubricant and direct compression lactose, there are unfavourable interactions with the pharmaceutically active ingredient in the tablet formulation resulting in unacceptably low assay figures.
I We have overcome this problem by including an inhibitor in the formulation to substantially prevent such interactions. We have also found that by mixing the ingredients except the lubricant and subsequently adding the lubricant and further mixing of the ingredients leads to the production of tablets with satisfactory hardness, dissolution and tabletting qualities.
Mixing using a dry blending technique is also preferred since the avoidance of granulating solutions confers active ingredient stability, the elimination of applied heating stages, particle size uniformity.
In each case, the formulation is a direct compression formulation. The ingredients were weighed out and all the ingredients except the lubricant (in these cases magnesium stearate) were added to a receptacle and dry blended for about 6 minutes. The magnesium stearate was then added and the mixture was blended for a further 2 minutes. Tablets were then formed from the blend by conventional direct compression techniques.
EXAM-1 A batch of tablets were prepared by direct compression. Each tablet had the following composition:- mg Oxybutynin chloride 119 mg DC Lactose 43 mg microcrystalline cellulose 12 mg c ro s povidone 1 mg magnesium stearate The tablets gave an assay of 97.9%.
EXAMPLE 2 A batch of tablets were prepared by direct compression. Each tablet had the following composition. mg Bumetanide 5 237.5 mg DC Lactose mg microcrystalline cellulose 25 mg crospovidone 2.5 mg magnesium stearate The tablets gave an assay of 97.4%.
EXAMPLE 3 A batch of tablets were prepared by direct compression Each tablet had the following composition. mg Bumetanide 237.5 mg DC Lactose 80 mg microcrystalline cellulose mg maize starch 2.5 mg magnesium stearate The tablets gave an assay of 98.2%.
EXAMPLE_4_ A batch of tablets were prepared by direct compression Each tablet had the following composition:- 2.5 mg Indapamide 82.75 mg DC Lactose 4 mg carboxymethyl starch 25 0.75 mg magnesium stearate The tablets gave an assay of 100.4%.
The invention is not limited to the embodiments hereinbefore described which may be varied in detail.
Claims (5)
1. A method for producing tablets of an active pharmaceutical ingredient comprising the steps of: mixing the*active pharmaceutical ingredient, 5 a lubricant, direct compression lactose, and an amount of an inhibitor to substantially prevent interaction between the direct compression lactose and the active pharmaceutical ingredient; and 10 directly compressing the mixture thus formed to form tablets.
2. A method as claimed in claim 1 wherein the method includes the step of mixing the ingredients except the lubricant; subsequently adding the lubricant; 15 and further mixing the ingredients, preferably the mixing is performed using a dry blending technique.
3. A method as claimed in any preceding claim wherein the inhibitor is a starch product or a derivative 20 thereof, alternatively the inhibitor is a crosspovidone based product.
4. A method of producing tablets of an active pharmaceutical ingredient substantially as hereinbefore described with reference to the 25 examples.
5. Tablets of an active pharmaceutical ingredient whenever prepared by a method as claimed in any preceding claim.
Priority Applications (13)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IES950586 IES65615B2 (en) | 1995-07-31 | 1995-07-31 | Pharmaceutical processing |
| EP00115840A EP1057479A1 (en) | 1994-12-14 | 1995-12-14 | Pharmaceutical tablet formulations for direct compression |
| PT95942265T PT800384E (en) | 1994-12-14 | 1995-12-14 | METHOD FOR PREPARING A PHARMACEUTICAL TABLET |
| IE950946A IE950946A1 (en) | 1994-12-14 | 1995-12-14 | Pharmaceutical tablet formulations. |
| PCT/IE1995/000062 WO1996018386A1 (en) | 1994-12-14 | 1995-12-14 | Pharmaceutical tablet formulations for direct compression |
| EP95942265A EP0800384B1 (en) | 1994-12-14 | 1995-12-14 | Pharmaceutical tablet formulations for direct compression |
| DE69520292T DE69520292T2 (en) | 1994-12-14 | 1995-12-14 | PHARMACEUTICAL PREPARATION FOR DIRECT INJECTION |
| ES95942265T ES2154744T3 (en) | 1994-12-14 | 1995-12-14 | FORMULATIONS OF PHARMACEUTICAL TABLETS FOR DIRECT COMPRESSION. |
| AT95942265T ATE199495T1 (en) | 1994-12-14 | 1995-12-14 | PHARMACEUTICAL PREPARATION FOR DIRECT COMPRESSION |
| DK95942265T DK0800384T3 (en) | 1994-12-14 | 1995-12-14 | Pharmaceutical tablet formulations for direct compression |
| GB9525598A GB2295966B (en) | 1994-12-14 | 1995-12-14 | Direct compression tablets |
| AU43539/96A AU4353996A (en) | 1994-12-14 | 1995-12-14 | Pharmaceutical tablet formulations for direct compression |
| GR20010400714T GR3035863T3 (en) | 1994-12-14 | 2001-05-15 | Pharmaceutical tablet formulations for direct compression |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IES950586 IES65615B2 (en) | 1995-07-31 | 1995-07-31 | Pharmaceutical processing |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IES950586A2 IES950586A2 (en) | 1995-11-01 |
| IES65615B2 true IES65615B2 (en) | 1995-11-01 |
Family
ID=11040836
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IES950586 IES65615B2 (en) | 1994-12-14 | 1995-07-31 | Pharmaceutical processing |
Country Status (1)
| Country | Link |
|---|---|
| IE (1) | IES65615B2 (en) |
-
1995
- 1995-07-31 IE IES950586 patent/IES65615B2/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| IES950586A2 (en) | 1995-11-01 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Patent lapsed |