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WO2016155682A1 - Nouvelle étape dans le processus d'enrobage de granules contenant de la tamsulosine hcl - Google Patents

Nouvelle étape dans le processus d'enrobage de granules contenant de la tamsulosine hcl Download PDF

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Publication number
WO2016155682A1
WO2016155682A1 PCT/CZ2016/000032 CZ2016000032W WO2016155682A1 WO 2016155682 A1 WO2016155682 A1 WO 2016155682A1 CZ 2016000032 W CZ2016000032 W CZ 2016000032W WO 2016155682 A1 WO2016155682 A1 WO 2016155682A1
Authority
WO
WIPO (PCT)
Prior art keywords
pellets
water
spraying
coating
process according
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.)
Ceased
Application number
PCT/CZ2016/000032
Other languages
English (en)
Inventor
Radka MALA
Alexandra DUMICIC
Jan DOHNAL
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.)
Zentiva KS
Original Assignee
Zentiva KS
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 Zentiva KS filed Critical Zentiva KS
Publication of WO2016155682A1 publication Critical patent/WO2016155682A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5026—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
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/18—Sulfonamides

Definitions

  • the invention relates to a process of coating pellets containing TamsuIosin.HCl.
  • the pellets provides with an acid resistant coating, with extended release of the said drug are subsequently capsuled into hard gelatine capsules.
  • TamsuIosin.HCl belongs to the group of drugs called alpha-adrenoreceptor blockers. Tamsulosin relaxes prostate muscles and the urethra. This enables easier flow of urine through the urethra, making it easier to urinate.
  • the present invention relates to pellets containing the active ingredient TamsuIosin.HCl, which are covered with a functional coating.
  • the coated pellets consist of the core, which contains the active ingredient, and a protective polymer-based coating that prevents releasing of the active ingredient in an acidic environment.
  • the pellet cores are produced by wet granulation followed by extrusion and spheronization.
  • the coating is applied in the form of an aqueous polymeric dispersion in an atomizing device.
  • the liquid can be applied onto the particles from the top, from the bottom, or tangentially.
  • Table 1 The composition presented in Table 1 is very similar, regardmg its quality, to the composition of the preparation that is disclosed by the patent US 4 772 475 (EP 0 194 838, EP 0 533 297).
  • Microcrystalline cellulose serves as the filler.
  • Eudragit ® L 30 D-55 copolymer of methacrylic acid and ethyl aery late 1 :1 (30 % dispersion)
  • Triethyl acetate and triacetin are added to the formulation as softeners.
  • Talc serves as an anti-adhesive ingredient.
  • the present invention relates to a process of producing a pharmaceutical composition of Tamsulosi HCl in the form of pellets coated with a copolymer of methacrylic acid and ethyl acrylate in the weight ratio of 1:1, the spraying with water being made onto freshly coated pellets.
  • the process provides an alternative pellet coating method to the methods that have already been described in the prior art.
  • the alternative consists in the added water spraying step. This step is inserted into the process after spraying with the coating polymer dispersion. During the coating process such conditions must be provided that the dispersion drops applied onto the pellets are given time to dry to such an extent that on contact with the device the coating should not get abraded or stick to the device wall.
  • the water evaporation rate must be sufficiently low to ensure coalescence of the polymer on the pellet surface.
  • no compact film layer is guaranteed, which can then contain fissures leading to a product of unacceptable quality.
  • additional spraying with water will ensure the required product quality even in case the optimum conditions cannot be achieved during the spray application of the polymeric coating dispersion. This may e.g. happen in case of an insufficient capacity of a peristaltic pump. If the pumping rate of the coating dispersion is low, the humidity in the system may be low and the solvent may evaporate too quickly.
  • the impossibility to achieve the optimum conditions may also be caused by very dry input air ensuring fluidization without the possibility to compensate it by quicker spraying. In these cases, which rather describe error conditions than the routine production, the product can be saved by additional water spraying. Water supplied to the system in any manner (spraying, fiuidizing air) serves as a softener and makes it possible to finalize the process of polymer coalescence on the pellet surface.
  • the step of spraying water onto freshly coated pellets is carried out before or after drying of the freshly coated pellets at the pellet temperature of 30 to 35°C for 2 to 5 hours, preferably for 3 to 4 hours.
  • the humidity of the output air is maintained between 63 and 73% RH.
  • the water spraying step is added to the process after the step of spray- application of the polymeric dispersion.
  • This step can also be added after the drying of the coated pellets. However, in such a case it may be necessary to repeat the drying to achieve the required humidity of the final coating pellets.
  • the manner of water spraying is governed by the spraying duration and spraying time.
  • the spraying rate is adjusted depending on the pellet temperature, which may achieve 30 to 35°C (typically 31°C).
  • the maximum temperature of the product is not determined by the decomposition temperature of Tamsulosin.HCl, which is stable up to about 230°C, but it is determined by the properties of the other auxiliary substances in the product.
  • the temperature of the product must not also be so high to cause softening of the polymer on the pellet surface, which would result in abrasion of the coating on contact with the device surface.
  • the product temperature is further controlled by the speed of the fluidizing air and the input air temperature.
  • the duration of the spraying is based on the coating properties that should be achieved. Generally, the required improvement of the acid resistance properties is achieved after 2 to 5 hours of spraying at the output humidity in the system between 55 to 75% RH. Humidity is supplied to the system with the fluidizing air and sprayed water. It is removed by the fluidizing air. It is important that the pellets get in contact with water. In an experiment wherein pellets were exposed to atmospheric humidity in the water vapour form, no improvement of the acid resistance properties of the functional coating was registered.
  • Tamsulosin pellets with extended release consists of the following steps:
  • the coated pellets are filled into hard gelatine capsules
  • Pellets coated with a functional polymeric film were prepared by the above mentioned producing process, comprising water spraying.
  • the composition of the pellets is presented in Table 3.
  • Table 4 contains the results of dissolution after 1 h at pH 1.0 (paddles, 100 rpm) before and after spraying of water.
  • experiment A water spraying was applied onto 100 g of coated pellets in a laboratory device. The spraying took 3.6 hours and the product temperature was maintained at 31°C. The spraying rate was 7.55 g / min, i.e. the total amount of 1631 g of water was sprayed onto the pellets. Related to the charge weight it amounted to 1631%.
  • Experiment B was conducted in a production plant with the coated pellet charge of 100 kg. The spraying took 3.0 hours and the product temperature was 30°C. In this case the spraying rate was 730 g / min.
  • the total amount of sprayed water was 131.4 kg, which represents 131.4%, related to the charge weight.
  • the linear flow rate of the fluidizing air and the input air humidity was comparable in both the cases.
  • the output air temperature was 62°C in both the cases. In both the experiments, the output air humidity was maintained between 63 and 73% RH.
  • the product temperature was 30 to 31 °C and it was achieved by the water flow rate since the other parameters remained constant during the experiment. The obtained results indicate that, the values of the above mentioned parameters of the process being maintained, it is the spraying duration that is essential for both the equipment sizes and not the quantity / relative quantity of sprayed water.
  • composition in combination with suitably selected process parameters ensured a product of the required quality.
  • additional application of water spraying improved the acid resistance of the coating to such an extent that during one hour in acidic media max. 10% of the active ingredient was released. This limit was not achieved before the application of the water spray.
  • the further dissolution profile in pH 6.8 media has the character of a product with extended release.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne un procédé de production d'une composition pharmaceutique contenant le principe actif Tamsulosine HCl sous forme de granules enrobées d'un copolymère d'acide méthacrylique et d'acrylate d'éthyle selon le rapport en poids de 1:1, de l'eau étant pulvérisée sur les granules fraîchement enrobées. La manière dont est pulvérisée l'eau est régie par la durée et le moment de pulvérisation.
PCT/CZ2016/000032 2015-03-30 2016-03-30 Nouvelle étape dans le processus d'enrobage de granules contenant de la tamsulosine hcl Ceased WO2016155682A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CZ2015-225A CZ2015225A3 (cs) 2015-03-30 2015-03-30 Nový krok ve způsobu potahování pelet obsahujících Tamsulosin.HCI
CZPV2015-225 2015-03-30

Publications (1)

Publication Number Publication Date
WO2016155682A1 true WO2016155682A1 (fr) 2016-10-06

Family

ID=55759419

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CZ2016/000032 Ceased WO2016155682A1 (fr) 2015-03-30 2016-03-30 Nouvelle étape dans le processus d'enrobage de granules contenant de la tamsulosine hcl

Country Status (2)

Country Link
CZ (1) CZ2015225A3 (fr)
WO (1) WO2016155682A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023072872A1 (fr) 2021-10-25 2023-05-04 Farmalíder, S.A. Suspension orale de tadalafil

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0194838A2 (fr) 1985-03-08 1986-09-17 Yamanouchi Pharmaceutical Co. Ltd. Formulation pharmaceutique à libération contrôlée
US20030147948A1 (en) * 2001-07-27 2003-08-07 Yamanouchi Pharmaceutical Co., Ltd Composition comprises sustained-release fine particles and manufacturing method thereof
WO2004043448A1 (fr) * 2002-11-14 2004-05-27 Synthon B.V. Pastilles pharmaceutiques a la tamsulosine
JP2005272347A (ja) * 2004-03-24 2005-10-06 Ohara Yakuhin Kogyo Kk 固形製剤の製造方法
WO2010066268A1 (fr) 2008-12-09 2010-06-17 Synthon B.V. Granules de tamsulosine pour une association à dose fixe
WO2014203137A2 (fr) * 2013-06-21 2014-12-24 Wockhardt Limited Compositions pharmaceutiques de tamsulosine ou ses sels
CZ27703U1 (cs) 2014-11-20 2015-01-12 Zentiva, K.S. Kapsle obsahující Tamsulosin.HCI v peletách s prodlouženým uvolňováním

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0194838A2 (fr) 1985-03-08 1986-09-17 Yamanouchi Pharmaceutical Co. Ltd. Formulation pharmaceutique à libération contrôlée
US4772475A (en) 1985-03-08 1988-09-20 Yamanouchi Pharmaceutical Co., Ltd. Controlled-release multiple units pharmaceutical formulation
EP0533297A1 (fr) 1985-03-08 1993-03-24 Yamanouchi Pharmaceutical Co. Ltd. Formulation pharmaceutique à libération contrôlée
US20030147948A1 (en) * 2001-07-27 2003-08-07 Yamanouchi Pharmaceutical Co., Ltd Composition comprises sustained-release fine particles and manufacturing method thereof
WO2004043448A1 (fr) * 2002-11-14 2004-05-27 Synthon B.V. Pastilles pharmaceutiques a la tamsulosine
JP2005272347A (ja) * 2004-03-24 2005-10-06 Ohara Yakuhin Kogyo Kk 固形製剤の製造方法
WO2010066268A1 (fr) 2008-12-09 2010-06-17 Synthon B.V. Granules de tamsulosine pour une association à dose fixe
WO2014203137A2 (fr) * 2013-06-21 2014-12-24 Wockhardt Limited Compositions pharmaceutiques de tamsulosine ou ses sels
CZ27703U1 (cs) 2014-11-20 2015-01-12 Zentiva, K.S. Kapsle obsahující Tamsulosin.HCI v peletách s prodlouženým uvolňováním

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
DATABASE WPI Section Ch Week 200573, Derwent World Patents Index; Class A96, AN 2005-707967, XP002757727, TANIGUCHI T; TERAI T; TOGO T: "Manufacture of a solid formulation, by adding liquid of methacrylic acid copolymer L, triethyl citrate, glyceryl monostearate, polysorbate-80 and water to drug granules, and ethyl cellulose, glyceryl monostearate and water to form coats" *
WANG J ET AL: "Preparation and evaluation of tamsulosin hydrochloride sustained-release pellets modified by two-layered membrane techniques", ASIAN JOURNAL OF PHARMACEUTICAL SCIENCES, vol. 10, no. 1, February 2015 (2015-02-01), pages 31 - 39, XP002757726 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023072872A1 (fr) 2021-10-25 2023-05-04 Farmalíder, S.A. Suspension orale de tadalafil

Also Published As

Publication number Publication date
CZ2015225A3 (cs) 2016-10-12

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