EP2086517A2 - Pharmaceutical dosage form - Google Patents

Pharmaceutical dosage form

Info

Publication number
EP2086517A2
EP2086517A2 EP07852324A EP07852324A EP2086517A2 EP 2086517 A2 EP2086517 A2 EP 2086517A2 EP 07852324 A EP07852324 A EP 07852324A EP 07852324 A EP07852324 A EP 07852324A EP 2086517 A2 EP2086517 A2 EP 2086517A2
Authority
EP
European Patent Office
Prior art keywords
dosage form
pharmaceutical dosage
form according
pantoprazole
pharmaceutical
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP07852324A
Other languages
German (de)
French (fr)
Inventor
Abdullah Uslu
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Nobel ILAC San VE Tic AS
Original Assignee
Nobel ILAC San VE Tic AS
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Nobel ILAC San VE Tic AS filed Critical Nobel ILAC San VE Tic AS
Publication of EP2086517A2 publication Critical patent/EP2086517A2/en
Withdrawn legal-status Critical Current

Links

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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2009—Inorganic compounds
    • 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
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • 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
    • A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • 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
    • A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
    • A61K9/2846—Poly(meth)acrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants

Definitions

  • pantoprazole formulation The preferred tablet formulation of pantoprazole formulation is explained in Example 1.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Inorganic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The present invention including pantoprazole active ingredient consists of pharmaceutical solid dosage form core tablet, an enteric-coating and a pre-coating between core tablet and enteric coating. Core tablet, contains the pantoprazole active ingredient together with sodium carboxymethylcellulose as binder and isomalt as filler.

Description

DESCRIPTION PHARMACEUTICAL DOSAGE FORM
Field of the Invention This present invention relates to a stable pharmaceutical dosage form including pantoprazole active ingredient or pharmaceutical acceptable salt.
Background of the Invention
Pantoprazole which is a proton-pump inhibitor derivative binds to H+, K+ ATPaz enzyme and inhibits it by turning into active form in acid environment in parietal cells canal lumen of stomach mucosa. Pantoprazole pressurize both the basal and inhibited the gastric acid secretion by H+, K+ ATPaz inhibition. The anti-secretary effect after enzyme inhibition lasts more than 24 hours.
The medicaments including pantoprazole active ingredient are used to treat duodenal and gastric peptic ulcer, gastroesophageal reflux disease and reflux esophagi; by the combination of two suitable antibiotics to reduce the replication of duodenal and gastric ulcer which occurs because of Helicobacter pylori.
Pantoprazole active ingredient (S)-5-methoxy-2-[(4-methoxy-3,5-dimethyl-2-pyridinile), is first disclosed in US patent US4758579.
To develop stable pantoprazole formulations from benzimidazole and the group of benzimidazole is very difficult because of the sensitivity to acidic environment, heat and humidity of the molecules.
To use the ancillary compounds which are commonly used and disclosed in EP244380 and EP 247983 patents cause problems in the stability of the final product.
European Patent application EP0589981 discloses stable pantoprazole formulation. It is stated that in this document commonly used binders and the fillers, such as lactose, microcrystalline cellulose or hydroxypropylcellulose cause stability problems in the pantoprazole formulation. In the same patent is explained that the problem can be solved by using mannitol as filler. European Patent EP0589981 discloses the use of a suitable binder (high molecular weighted binder) preferably PVP and/or hydroxypropylcellulose (HPMC) to obtain the tablet in a desired strength. In addition it is stated in this document that using sodium carbonate as basic material in the formulation. To add basic material in the active ingredient formulations of benzimidazole derivatives is a known technique.
When the patent above and the other patent of the known technique, the binder which will be used in the stable pharmaceutical compound including pantoprazole, should be ' compatible with other ancillary compounds and should have the suitable binding capability to make the tablet in the desired strength.
Sodium carboxymethylcellulose is more basic binder than hydroxypropylcellulose and PVP and it is obvious advantage for the formulation especially stability. But, in the patent EP0589981 which mannitol is used as filler, using sodium carboxymethylcellulose as stable making binders is not stated. The binders in this patent are restricted with PVP and hydroxypropylmethylcellulose. The reason for that is the pantoprazole formulation including mannitol does not provide the desired strength values. Although sodium carboxymethylcellulose is more desired than HPMC and PVP for their basic properties, they are not used in the pantoprazole tablet formulations because of the undesired strength values.
Another document EP1257256 Bl explains a group filler including mannitol to be used in the pellet formulation. This patent protects filler materials, mannitol, sucrose, fructose, fructo-oligo saccharine, inulin, sorbitol, xylitol, inositol, isomalt and maltodextrin to be used as pellet formulation. But this patent does not give any information about neither the usage of these fillers in the pantoprazole formulation nor tablet formulations. In addition the most filler used in this patent causes staining in the pantoprazole formulations.
The objective of the present invention is to develop a new pantoprazole tablet formulation having suitable stability values and administrated orally.
Another objective of the invention is to develop a basic filling material and a pantoprazole tablet formulation conformable with this filler. The pantoprazole active ingredient containing subject invention includes pharmaceutical solid dosage form core tablet, an enteric coating and a pre-coating between core tablet and enteric coating.
The core tablet includes both sodium carboxymethylcellulose as binder and isomalt as filler.
To use isomalt as filler in pantoprazole formulation contribute the production of stable pantoprazole formulation.
In addition using isomalt filler with sodium carboxymethylcellulose unexpectedly provides the desired core tablet strength values.
In the formulation of the subject invention, the core tablet includes also tri-basic sodium phosphate as basic material.
In the formulation of the subject invention, the core tablet includes also sodium stearil fumarate as lubricant agent.
The protective coating between core tablet and enteric coating consist of Pharmacoat 603, PVP K 25, Sepisperse AP3232, Propylene glycol.
The enteric coating includes Eudragit®, Citroflex and Simeticone Emulsion or Dimethicone Emulsion.
The preferred tablet formulation of pantoprazole formulation is explained in Example 1.
Examplel
Pantoprazole 40 mg enteric-coated tablet formulation:
The open formula of the pantoprazole containing pharmaceutical compound is shown above and the production process is given below.
In the first step of the production, the aqueous solution of NaCMC - 7MXF was prepared. Some of tri-basic phosphate was added and the granulation solution was prepared (pH > 10). The pantoprazole sodium sesquihydrate transferred into the wet granulation cauldron and some of crospovidone, isomalt LM-PF, anhydrous tri-basic sodium phosphate and rest of NaCMC — 7MXF were mixed to obtain a suitable mixture. This mixture is granulated by granulation solution in a fluidized bed. Obtained granules, rest of crospovidone and sodium stearate fumarate were mixed and the solid mixture was made tablet by suitable tablet machine. The pre-coating process and then enteric-coating process were made respectively.
Two stability tests were performed to obtain tablets. In the first stability test, the tablets were placed open in boxes and the boxes were stored at 4O0C, 75 % relative humidity and at 6O0C the tablets were examined by visual observation and the results are shown below in table II.
For the second stability test the tablets were packed in aluminum/aluminum blisters and stored under accelerated stability test conditions of 300C, 65 % relative humidity and 400C, 75 % relative humidity for 6 months and the obtained results are below.
The results obtained from the stability tests clearly show that the ancillary materials used in the pantoprazole formulation are conformable with pantoprazole and the formulation is stable.

Claims

1. Pharmaceutical dosage form including core tablet consists of pantoprazole as active ingredient or an pharmaceutical acceptable salt, isomalt as filler, sodium carboxymethylcellulose as binder, at least one pharmaceutical suitable disintegrant, one basic material and one lubricant.
2. Pharmaceutical dosage form according to claim 1, including pantoprazole as active ingredient.
3. Pharmaceutical dosage form according to claim 1 or 2, including crospovidone as disintegrant.
4. Pharmaceutical dosage form according to claim 1 or 3, including anhydrous tri- basic sodium phosphate as basic material.
5. Pharmaceutical dosage form according to claim 1 or 4, including sodium stearil fumarate as lubricant.
6. Pharmaceutical dosage form according to claim 1 or 5, which administrated orally.
7. Pharmaceutical dosage form according to claim 1 or 6, which is in the tablet form.
8. Pharmaceutical dosage form according to claim 1 or 7, including enteric-coating.
9. Pharmaceutical dosage form according to claim 1 or 8, consists of Pharmacoat 603, PVP K 25, Propylene glycol and take part between core tablet and enteric coating.
10. Use of the pharmaceutical dosage form according to claim 1 or 9, in the manufacture of a medicine for the treatment of the a duodenal and gastric peptic ulcer, gastro-esophageal reflux disease and reflux esophagi; by the combination of two suitable antibiotics to reduce the replication of duodenal and gastric ulcer which occurs because of Helicobacter pylori.
EP07852324A 2006-10-10 2007-10-10 Pharmaceutical dosage form Withdrawn EP2086517A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
TR2006/05624A TR200605624A2 (en) 2006-10-10 2006-10-10 Pharmaceutical dosage form
PCT/TR2007/000121 WO2008045009A2 (en) 2006-10-10 2007-10-10 Pharmaceutical dosage form

Publications (1)

Publication Number Publication Date
EP2086517A2 true EP2086517A2 (en) 2009-08-12

Family

ID=39283297

Family Applications (1)

Application Number Title Priority Date Filing Date
EP07852324A Withdrawn EP2086517A2 (en) 2006-10-10 2007-10-10 Pharmaceutical dosage form

Country Status (3)

Country Link
EP (1) EP2086517A2 (en)
TR (1) TR200605624A2 (en)
WO (1) WO2008045009A2 (en)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105380919A (en) * 2015-11-20 2016-03-09 世贸天阶制药（江苏）有限责任公司 Pantoprazole sodium enteric-coated tablet and preparation method thereof

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SE9402431D0 (en) * 1994-07-08 1994-07-08 Astra Ab New tablet formulation
DE19752843C2 (en) * 1997-11-28 2003-01-09 Byk Gulden Lomberg Chem Fab Pharmaceutical preparation in tablet or pellet form for pantoprazole and omeprazole
GB0003782D0 (en) * 2000-02-17 2000-04-05 Dumex Ltd As Process

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2008045009A2 *

Also Published As

Publication number Publication date
TR200605624A2 (en) 2008-05-21
WO2008045009A2 (en) 2008-04-17
WO2008045009A3 (en) 2008-12-31

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