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WO2018131010A2 - Chambre dynamique pour tests de perméabilité in vitro - Google Patents

Chambre dynamique pour tests de perméabilité in vitro Download PDF

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Publication number
WO2018131010A2
WO2018131010A2 PCT/IB2018/052688 IB2018052688W WO2018131010A2 WO 2018131010 A2 WO2018131010 A2 WO 2018131010A2 IB 2018052688 W IB2018052688 W IB 2018052688W WO 2018131010 A2 WO2018131010 A2 WO 2018131010A2
Authority
WO
WIPO (PCT)
Prior art keywords
dissolution vessel
chambers
cover
magnetized material
vitro
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/IB2018/052688
Other languages
English (en)
Other versions
WO2018131010A3 (fr
Inventor
Antonio ARIAS
Audino MONTENEGRO
Sebastian VELARDE
Christian GÓMEZ
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.)
Absorption Systems
Original Assignee
Absorption Systems
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 Absorption Systems filed Critical Absorption Systems
Publication of WO2018131010A2 publication Critical patent/WO2018131010A2/fr
Publication of WO2018131010A3 publication Critical patent/WO2018131010A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N13/00—Investigating surface or boundary effects, e.g. wetting power; Investigating diffusion effects; Analysing materials by determining surface, boundary, or diffusion effects
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/08—Investigating permeability, pore-volume, or surface area of porous materials
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/04—Closures and closing means
    • B01L2300/041—Connecting closures to device or container
    • B01L2300/042—Caps; Plugs
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/04—Closures and closing means
    • B01L2300/046—Function or devices integrated in the closure
    • B01L2300/047—Additional chamber, reservoir
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0609—Holders integrated in container to position an object
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0681—Filter
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0832—Geometry, shape and general structure cylindrical, tube shaped
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N13/00—Investigating surface or boundary effects, e.g. wetting power; Investigating diffusion effects; Analysing materials by determining surface, boundary, or diffusion effects
    • G01N2013/006—Dissolution of tablets or the like
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
    • G01N15/08—Investigating permeability, pore-volume, or surface area of porous materials
    • G01N2015/0813—Measuring intrusion, e.g. of mercury

Definitions

  • the present invention may be included in the technical field of health science, in particular in models for studying dissolution and absorption models occurring simultaneously in the stomach and intestine, such as in vitro permeability assays, in such a way that these are reproduced with higher accuracy.
  • medicaments administered orally in the solid form thereof are disintegrated and dissolved in the stomach and are absorbed in the intestine.
  • the device of the invention allows concomitant assessment of (a) the dissolution characteristics of intact (without being milled or processed) tablets or capsules and in the actual clinical size thereof, and of (b) permeability of the active principles through a cell membrane.
  • the device of the invention will simulate the gastrointestinal condition by using the expected dose/gastric volume ratio after swallowing the tablet or capsule with a glass of water, and after incorporation of the relevant physiological components (bile acid, taurocholic acid, in the mucosal chamber, and plasmatic protein, albumin, in the serum chamber).
  • relevant physiological components bile acid, taurocholic acid, in the mucosal chamber, and plasmatic protein, albumin, in the serum chamber.
  • the distinctive physiological significance of the device of the invention will lead to a higher and better in vivo performance of medicaments based on the in vitro dissolution and permeability assays results. Furthermore, it will cause a great positive impact on development and optimization of medicament formulations since the most novel molecules are Class 2 compounds (low solubility and high permeability), a type of compound which in general requires substantial efforts in their formulation, even when this does not guarantee success thereof. It will likewise allow assessment of the food effect on absorption of orally administered medicaments of Class 2.
  • the device of the invention will have the following functions: (i) providing for understanding of the relationship between the medicament dissolution (tablet or capsule) and permeability of the active principle; (ii) reducing the number of assays performed in animals, such as dogs, for routine assessment of formulations, for which, furthermore, there are no possible alternatives; (iii) optimizing in vitro formulations for increasing the success probability in the bioequivalence studies; and (iv) assessing the food effect of food on absorption of the orally administered medicaments of Class 2, among others, given that the prior studies have found that the mostly used animal model, the dog, is not capable of suitable prognosis of the effect of food in humans.
  • a first aspect of the invention refers to a dynamic chamber for in vitro permeability assays characterized by having a cylindrical shape and comprising:
  • the filter may be made of polycarbonate, a fabric or any other biomaterial, such that the biological permeability process can be produced, and
  • Fixing the filter by means of magnets is a safer mechanism, thus preventing thread-like fixing mechanisms from damaging said filters or the biomaterials.
  • Another aspect of the present invention refers to a simulating gastrointestinal device for in vitro permeability assays characterized in that it comprises: - a U-shaped dissolution vessel;
  • dissolution vessel cover divided into two parts attached to each other by means of a magnetized material and having suitable orifices for vertically accommodating and fitting at least two dynamic chambers, described in the present invention, thus being arranged inside the dissolution vessel, and
  • the dissolution vessel cover accommodates four dynamic chambers and comprises, at the inner part thereof, anchoring orifices for the magnetized material of the chamber cover and two openings on the surface thereof.
  • FIG.1 It shows a front and side view of a dynamic chamber of the invention.
  • FIG.2 It shows a side and upper view of the configuration of the cover for accommodating four dynamic chambers.
  • FIG.3 it shows a cross-sectional view of the device of the invention.
  • FIG.1 This first image represents a general view of the dynamic chamber, in the most basic form thereof, and shows its main characteristics. It shows the chamber (1 ), the cover (2) with the magnetized material that will subsequently fix it to said cover (2) and that will also allow direct sampling (6a) with pipettes or any other device, the cover/washer (3) fixing the filters (3a) to the chamber with a magnetized material and the protrusions (4) intended for mitigating the possible turbulences in the liquid in the dissolution vessel once it starts being stirred. Furthermore, it shows the ducts (5) which will be in charge of adding sampled liquid and the ducts (6) in charge of removing said liquid so as to analyse it as a sample.
  • FIG.2 shows the cover configuration for accommodating four dynamic permeability chambers (7).
  • This cover comprises two parts (9, 10), which are attached to each other by a magnetized material (1 1 ).
  • the figure also shows the openings (8) the cover is provided with so as to perform a manual sampling.
  • FIG.3 This image shows the position of the cover (13) and the permeability dynamic chambers (1 ) in a dissolution vessel (14) in a cross-sectional view, as well as the stirring blade (15), typical of any standard dissolution apparatus, and the fixing points by means of a magnetized material of the chambers (12). Said figure also shows the expected level (16) of the liquid or fluid using the dissolution vessel.
  • the following is a description of an example of a typical assay to be realized by the device of the invention:
  • a significant amount of liquid is introduced at a pH being similar to that of the stomach (distilled water, in case of not using a biorelevant means, or any other biorelevant fluid with the suitable pH) in the dissolution vessel (14) until the level (16) indicated by the laboratory operator.
  • the tablet or tablets of medicaments to be analysed and stirring is started by the standard stirring blade (15).
  • the pH of the liquid is modified so as to adapt it to the conditions expected in the intestine.
  • the permeability dynamic chambers (1 ) are introduced, having previously fitted therein filters or any other bio-material containing cells or tissues being the expected for the permeability process to be produced from the chamber outer side (17) or donor, to the inner side (17) or receptor. Meanwhile, stirring continues with the standard stirring blade (15). According to what is established by the assay protocol, sampling is performed at known intervals, using the inner ducts of the chamber (6) (for an automatic sampling process) or the upper opening of said chamber (6a) (for manual sampling). The operator shall also be able of taking samples from the donor side at previously established intervals thanks to the openings (8) that the dissolution vessel has.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • Physics & Mathematics (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • Dispersion Chemistry (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Investigating Or Analysing Biological Materials (AREA)

Abstract

L'invention concerne une chambre dynamique pour tests de perméabilité de forme cylindrique comprenant un coude arrondi au niveau de sa partie inférieure conjointement avec un filtre accouplé au moyen d'une fixation par aimant et de saillies sur les côtés de celle-ci. De plus, l'invention concerne également un dispositif de simulation gastro-intestinale pour des tests de perméabilité in vitro comprenant une chambre dynamique accouplée au niveau de celui-ci, dans un ensemble de quatre, au couvercle d'un récipient de dissolution standard.
PCT/IB2018/052688 2018-04-13 2018-04-18 Chambre dynamique pour tests de perméabilité in vitro Ceased WO2018131010A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
PA9210301 2018-04-13
PA92103 2018-04-13

Publications (2)

Publication Number Publication Date
WO2018131010A2 true WO2018131010A2 (fr) 2018-07-19
WO2018131010A3 WO2018131010A3 (fr) 2018-10-25

Family

ID=62840282

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2018/052688 Ceased WO2018131010A2 (fr) 2018-04-13 2018-04-18 Chambre dynamique pour tests de perméabilité in vitro

Country Status (1)

Country Link
WO (1) WO2018131010A2 (fr)

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020176800A1 (en) * 2001-05-09 2002-11-28 Henry Richard A. Curved miniature liquid chromatography column
JP2011506934A (ja) * 2007-12-06 2011-03-03 ペイン セラピューティクス インコーポレイテッド 溶解試験装置および試験のための方法
WO2011062633A1 (fr) * 2009-11-19 2011-05-26 Resmed Motor Technologies, Inc. Soufflerie
JP2013524257A (ja) * 2010-04-12 2013-06-17 ディステック，インコーポレーテッド 溶出試験用容器カバー
US9128017B2 (en) * 2013-03-19 2015-09-08 Rarecyte, Inc. Device, systems and methods for analyzing a target analyte

Also Published As

Publication number Publication date
WO2018131010A3 (fr) 2018-10-25

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