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Immediate release tablet

a tablet and release technology, applied in the field of immediate release tablets, can solve the problems of inability to give unacceptable tablets with very low hardness, poor quality of granules, and inability to dissolve variables in time,

Inactive Publication Date: 2005-09-22
FORSMAN SIGBRIT +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0016] The formulation according to the invention comprises the thrombin inhibitor, a filler or a combination of fillers, said filler / fillers having disintegrant properties (due to swelling) and, optionally, non swelling filler(s) disintegrant(s), binder(s) and / or lubricant(s).

Problems solved by technology

This variability in dissolution is not acceptable for safe, efficient and convenient therapy.
These two compositions gave very poor quality of the granulates, which gave unacceptable tablets with very low hardness.

Method used

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Examples

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working examples

Example 1

Drug Dissolution from Tablets According to the Invention

[0034] IR tablets of the thrombin inhibitor, Compound A, were prepared by mixing Compound A microcrystalline cellulose, sodium starch glycollate and mannitol The mixture was moistured with a suitable amount of polyvinylpyrrolidone K 90 dissolved in water. After drying, the granulate was milled and then mixed with sodium stearyl fumarate and compressed to tablets.

mg / tablCompound A24Microcrystalline cellulose (MCC pH 101)140Sodium starch glycollate16Mannitol16Polyvinylpyrrolidone K 9015Waterq.s.Sodium stearyl fumarate2Punches:9mmTablet weight:213mgHardness:110N

[0035] The obtained tablets were analysed with regard to dissolution of Compound A using a USP dissolution apparatus No. 2 (paddle), 100 rpm, 500 ml. The dissolution medium used had a temperature of 37° C. Two different dissolution medium were used, 0.1 M HCl pH 1 and phosphate buffer pH 6.8 (ionic strength 0.1). The amount of Compound A released was determined...

example 1b

Drug Dissolution from Tablets According to the Invention

[0037] IR tablets of thrombin inhibitor, Compound A were prepared by mixing Compound A, microcrystalline cellulose and maize starch and the mixture was moistured with a suitable amount of maize starch (paste). After drying the granulate was milled and then mixed with polyvinylpyrrolidone crosslinked. Finally the sodium stearyl fumarate was admixed and the granulate was compressed into tablets.

mg / tablCompound A30Microcrystalline cellulose115Maize starch55Maize starch (paste)6Waterq.s.Polyvinylpyrrolidone crosslinked10Sodium stearyl fumarate2.2Punches:8.5mmTablet weight:219mgHardness:110N

[0038] The obtained tablets were analysed for dissolution of Compound A according to the method described in Example 1. Results are shown in FIG. 2. After 30 minutes the amount of Compound A dissolved was 100% (average n=3) in 0.1 M HCl and 97% (average n=3) in phosphate buffer pH 6.8.

example 2

Drug Dissolution from Tablets According to the Reference

[0039] Lachman ((The theory and practice of industrial pharmacy 1986,343, appA) describes another composition and manufacturing of a “standard” granulate for an IR tablet. IR tablets of the thrombin inhibitor, Compound A were prepared according to this method by mixing Compound A, tricalcium phosphate and the mixture was moistured with pre-gelatinated maize starch dissolved in water. After drying the granulate was milled and then mixed with talc Finally, the mineral oil was admixed and the granulate was compressed to tablets.

Compound A24Tricalcium phosphate100Pregelatinized starch15Waterq.s.Talc60Mineral oil, light4Punches:9mmTablet weight:198mgHardness:12N

[0040] The obtained tablets were analysed for dissolution of Compound A according to the method described in Example 1. Results are shown in FIG. 2. After 30 minutes the amount of Compound A dissolved was 40% (average n=3) in 0.1 M HCl and 5% (average n=3) in phosphate buf...

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Abstract

A new oral IR formulation in solid form for a low molecular weight thrombin inhibitor having pH dependant dissolution, characterized in that the formulation comprises a filler or a combination of fillers having disintegrant properties in an amount higher than 35% w / w of the formulation.

Description

FIELD OF THE INVENTION [0001] The invention relates to a solid dosage form of a low molecular weight thrombin inhibitor formulated as immediate release (IR) tablets as well as a process for manufacture thereof. The invention also relates to the medical use of the formulation in the prophylaxis and / or treatment of thromboembolism. BACKGROUND OF THE INVENTION [0002] The thrombin inhibitor, used in the formulation of the present invention is a low molecular weight drug with pH dependent solubility. It is characterised by a low solubility at basic pH which is dramatically increased in the protonated form at acidic pH. Thus, upon administration in conventional IR formulations, fast dissolution of the drug is obtained in acidic pH while markedly slower dissolution is obtained at more neutral pH. This variability in dissolution is not acceptable for safe, efficient and convenient therapy. The present invention provides an immediate release formulation based on conventional manufacturing pr...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61KA61K9/14A61K9/20A61K9/22A61K31/397A61K38/00A61K38/04A61K38/54A61K38/55A61K47/10A61K47/36A61K47/38A61PA61P7/00A61P7/02A61P43/00
CPCA61K9/2009A61K9/2018A61K9/2027A61K47/38A61K9/2059A61K31/397A61K9/2054A61P43/00A61P7/00A61P7/02A61K9/20
Inventor FORSMAN, SIGBRITKARLSSON, CHRISTERKARLSSON, MAGNUS
Owner FORSMAN SIGBRIT