CA2214998A1 - Testing vessel - Google Patents

Testing vessel Download PDF

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Publication number
CA2214998A1
CA2214998A1 CA002214998A CA2214998A CA2214998A1 CA 2214998 A1 CA2214998 A1 CA 2214998A1 CA 002214998 A CA002214998 A CA 002214998A CA 2214998 A CA2214998 A CA 2214998A CA 2214998 A1 CA2214998 A1 CA 2214998A1
Authority
CA
Canada
Prior art keywords
vessel
dissolution testing
testing
dissolution
insert
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.)
Abandoned
Application number
CA002214998A
Other languages
French (fr)
Inventor
Stephen George Barnwell
Stephen John Burns
Simon Higginbottom
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.)
Cortecs Ltd
Original Assignee
Individual
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 Individual filed Critical Individual
Publication of CA2214998A1 publication Critical patent/CA2214998A1/en
Abandoned legal-status Critical Current

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Classifications

    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N13/00Investigating surface or boundary effects, e.g. wetting power; Investigating diffusion effects; Analysing materials by determining surface, boundary, or diffusion effects
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/15Medicinal preparations ; Physical properties thereof, e.g. dissolubility
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N13/00Investigating surface or boundary effects, e.g. wetting power; Investigating diffusion effects; Analysing materials by determining surface, boundary, or diffusion effects
    • G01N2013/006Dissolution of tablets or the like

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  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Pathology (AREA)
  • General Physics & Mathematics (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Analytical Chemistry (AREA)
  • Physics & Mathematics (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Food Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Molecular Biology (AREA)
  • Biophysics (AREA)
  • Medicinal Preparation (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Sampling And Sample Adjustment (AREA)
  • Devices For Use In Laboratory Experiments (AREA)

Abstract

A dissolution testing vessel comprising means which prevent a formulation undergoing dissolution testing from floating freely at the surface of the testing medium, but which do not prevent the testing medium from moving freely within the vessel. In particular, the means consists of a mesh or grille.

Description

-CA 022l4998 l997-09-09 TESTING VESSEL

This invention relates to a dissolution testing vessel, and in particular to a vessel for testing dissolution of pharmaceutical formulations, particularly buoyant pharmaceutical formulations.

In the field of pharmaceutical formulations there exists a need to study the behaviour of the formulations in vitro in such a way that the in vivo behaviour of the ~ormulations can be predicted. Many different types of formulation are produced, for example, slow-release formulations which are designed to release active ingredient(s) over a given period of time at an approximately constant rate.

Other formulations may be designed to release an initial "burst" of active ingredient followed by a steady-state release thereafter. For these various types of formulatlon, a reliable method of assessing dissolution in vivo and consequently analysing the rate of release of active ingredient(s) is required.

WO-A-9206680 is an example of an application relating to novel pharmaceutical formulations. In that disclosure dissolution testing is carried out using a method based upon the USP XXII dissolution test for tablets and capsules. This test is designed to subject the samples to an environment similar to that found in the intestine.
In that test a dissolution apparatus is used, again as specified by USP XXII. This essentially consists of a dissolution vessel into which is placed a buffered medium in which the dissolution testing of the pharmaceutical CA 022l4998 l997-og-og formulation will be carried out The sample is simply "dropped" into the medium and is allowed to float ~reely at the surface. The body o~ the medium is agitated by means of a paddle which is rotated. Paddle height is adjusted so that the top edge of the blade is level with the surface of the liquid. Then, at various time points throughout the test, aliquots of the dissolution medium can be removed and replaced with fresh buffer. These aliquots can then be tested to determine the amount of active ingredient(s) released from the sample formulation. This method is described in detail by Burns et al, Int. J. Pharmaceutics (1995) (in press).

There is, however, a problem with this adaptation of a traditional type testing method, in that since the sample can float freely at the surface of the liquid it can in fact be caught up by the paddle and indeed the formulation under test could even stick to the paddle.
Clearly, this may result in a delay in the breakdown of the formulation, and hence release of active ingredient(s), by virtue of the reduced mechanical action of the paddle on an erodible formulat~ion.

There thus exists a need to provide a dissolution testing vessel which overcomes this problem and allows the dissolution testing to be carried out on pharmaceutical formulations without any mechanical interaction between the formulation and the means used to agitate the medium in which the testing is being carried out. There is also required a means of assessing drug release from floating dosage forms without the sampling errors encountered when the dosage form is floating close to the surface of the dissolution medium.

CA 02214998 1997-09-og Similarly, it would be useful to have dissolution testing apparatus which could be used to assess drug release reliably ~rom a sinking, erodible, dosage form.

Thus, the present invention provides a dissolution testing vessel comprising means which prevent a ~ormulation undergoing dissolution testing ~rom ~loating ~reely at the sur~ace o~ the testing medium, but which do not prevent the testing medium ~rom moving ~reely within the vessel.

In a pre~erred embodiment, the means will also prevent a formulation undergoing dissolution testing ~rom sinking to the bottom o~ the testing medium.
The invention there~ore provides a testing vessel which will prevent the mechanical interaction with the means o~
agitation described above. In particular, the testing vessel o~ the invention is suitable ~or testing dissolution o~ both buoyant pharmaceutical ~ormulations and sinking erodible dosage ~ormulations.

Suitably, the means provided divide the vessel into at least two portions, while at the same time allowing the testing medium to move ~reely between those portions. In a pre~erred embodiment o~ the invention the means consists o~ an insert, which is provided as a mesh or grille and typically will have substantially the same diameter as that o~ the inner wall o~ the vessel.
Suitably this can be made of stainless steel.

i A particularly convenient way o~ allowing the insert to be held in place is to provide the vessel with one or more projections which project inwardly ~rom the wall o~

CA 02214998 1997-og-og W096/28717 PCT/GB9G/OC~93 the vessel and on which the insert can rest.

Alternatively, a continuous projection can be provided which runs ~or substantially the whole o~ the inner circum~erence o~ the vessel, eg a collar, ridge or shoulder. Thus, the insert can simply be dropped into the interior or the vessel and will sit on the collar, ridge or shoulder.

Suitably, the one or more projections, or continuous projection respectively, can be ~ormed as part o~ the vessel itsel~. This is particularly the case if the vessel is made o~ plastic or glass.

There~ore, in use, the pharmaceutical ~ormulation under test will remain below the insert (i~ it is a ~loating dosage ~orm) and will not be free to ~loat at the sur~ace. I~, however, it is a slnking erodible dosage ~orm, it can rest on the top o~ the insert. The medium itsel~ is still agitated by means o~ a paddle or paddles and the normal aliquots can be taken at appropriate time points to determine the amount o~ active ingredient(s) released.

The mechanical interaction between the means, ~or example an insert, and the ~ormulation, provides a suitable means o~ mechanical erosion, whether the dosage ~orm is a ~loating type or sinking type, and there~ore mimics the e~ect o~ the gastrointestinal tract in vivo. Unlike the paddle set to sur~ace method described by Burns et al, 1995 (supra), there is little tendency ~or the ~ormulation to stick to the means.

A pre~erred embodiment o~ the invention (used to assess CA 02214998 1997-og-og a ~loatlng dosage form) will now be descrlbed with re~erence to the accompanying drawing in which:

Fiaure l: is a sectional view o~ a pre~erred embodiment o~ the invention.

In Figure l can be seen a sectional view o~ a pre~erred vessel(l) o~ the invention. The vessel(l) is moulded with a continuous indentation(2) which runs along the entire circumference o~ the vessel. This e~ectively divides the vessel into a lower portion(3), which represents approximately one third o' the vessel's volume, and an upper portion(4). The provision o~ the indentation means that there is also provided a shoulder or ridge(5) which runs ~or the whole o~ the internal circum~erence o~ the vessel(l). An insert(6) is simply dropped into the vessel(l) and will rest upon the shoulder or ridge(5). A pharmaceutical ~ormulation undergoing testing will be placed in the vessel be~ore the insert(6) is dropped in and once the testing medium has been poured into the vessel the pharmaceutical formulation will remain within the lower portion(3) o~
the vessel(l) and will be prevented ~rom ~loating ~reely at the sur~ace o~ the testing medium by the insert(6).
EXAMPLE l: Comparison of Modi~ied and Existing Dissolution A dissolution study was carried out with a ~loating dosage ~orm, size '0' enteric-coated capsules containing a granule preparation o~ salmon calcitonin with a potency o~ 400 iu per capsule. The dissolution medium, volume 900 ml, was maintained at 37~C + 1~C and contained 5.84 g~ disodium hydrogen orthophosphate, 4.61 g l-CA 022l4998 l997-09-09 potassium dihydrogen orthophosphate, 2.00 g l-l sodium cholate and 1.00 g l-l sodium deoxycholate adjusted to pH
6.8. To determine the release of salmon calcitonin from the floating capsules, 5 ml samples of dissolution medium were removed for analysis. Samples were removed at specific intervals (eg 10, 15, 20, 25 min), up to 30 min, in each case the volume being replaced with fresh dissolution medium. The calcitonin content of the samples was determined by a specific ELISA for salmon calcitonin and quantified by comparison with authentic standards.

The two dissolution methods compared were as follows:

METHOD A - BP Type II apparatus with the paddles set to the surface of the dissolution medium as described by Burns et al (1995), Int. J. Pharm. (in press);

METHOD B - the present invention.
The paddle rotation speed in both cases was 100 rpm.

Results The results of the study comparing the two dissolution methods are shown in Table 1.

W 096/28717 PCT/~b9C/C~53 TA~3LE 1 Time Standard Present (min) Method Invention A B
O O O
~2 <2 2.5 + 27 (~200) 22 + 19 (95) 20 + 32 (160) 54 + 21 (39) 50 + 24 (48) 82 + 7 (9) 73 + 2 (3) 90 + 8 (9) The values are means o~ 6 determinations + SD, with the coe~icient o~ variance shown in brackets, and are expressed as percentage salmon calcitonin released ~rom the dosage ~orm.

The results in Table 1 show that the extent and rate o~
calcitonin release ~rom a ~loating dosage ~orm is considerablv less than using the method described in the present invention. Another observation is the reduced variability in the measurements at each point with the present invention compared with the standard method illustrated by the lower coe~icient o~ variance.

The skilled man will appreciate that any suitably shaped vessel can be used, o~ any suitable material. In addition, the means provided with the vessel ~or preventing the pharmaceutical formulation ~rom ~loating ~reely at the sur~ace o~ the testing medium can simply be adapted to the vessel shape. All such variations are intended to be within the scope o~ the present invention.

Claims (12)

CLAIMS:
1. A dissolution testing vessel comprising means which prevent a formulation undergoing dissolution testing from floating freely at the surface of the testing medium, but which do not prevent the testing medium from moving freely within the vessel.
2. A dissolution testing vessel as claimed in claim 1 wherein the means comprises an insert.
3. A dissolution testing vessel as claimed in claim 2 wherein the insert has substantially the same diameter as the inner wall of the vessel.
4. A dissolution testing vessel as claimed in claim 2 or claim 3 wherein the insert consists of a mesh or grille.
5. A dissolution testing vessel as claimed in any one of claims 2 to 4 wherein the insert is made of stainless steel.
6. A dissolution testing vessel as claimed in any one of claims 1 to 5 wherein the vessel is provided with one or more projections projecting inwardly from the interior wall of the vessel.
7. A dissolution testing vessel as claimed in any one of claims 1 to 5 wherein the vessel is provided with a continuous projection, projecting inwardly from the interior wall of the vessel, which runs for substantially the whole of the inner circumference of the vessel.
8. A dissolution testing vessel as claimed in claim 6 or claim 7 wherein the one or more projections or continuous projection respectively are formed as part of the vessel itself.
9. A dissolution testing vessel as climed in any one of claims 1 to 8 which is constructed of glass or plastic.
10. A dissolution testing vessel as claimed in claim 1 which is for use with pharmaceutical formulations.
11. The use of a dissolution testing vessel as defined in any one of claims 1 to 10 in the dissolution testing of a pharmaceutical formulation.
12. A dissolution testing vessel as claimed in claim 1 substantially as hereinbefore described with reference to the accompanying drawings.
CA002214998A 1995-03-10 1996-03-04 Testing vessel Abandoned CA2214998A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9504893.0 1995-03-10
GBGB9504893.0A GB9504893D0 (en) 1995-03-10 1995-03-10 Testing vessel

Publications (1)

Publication Number Publication Date
CA2214998A1 true CA2214998A1 (en) 1996-09-19

Family

ID=10771008

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002214998A Abandoned CA2214998A1 (en) 1995-03-10 1996-03-04 Testing vessel

Country Status (12)

Country Link
EP (1) EP0815427A1 (en)
JP (1) JPH11503517A (en)
KR (1) KR19980702844A (en)
AU (1) AU4885396A (en)
BR (1) BR9607230A (en)
CA (1) CA2214998A1 (en)
FI (1) FI973639A0 (en)
GB (1) GB9504893D0 (en)
IL (1) IL117407A0 (en)
NO (1) NO974156D0 (en)
WO (1) WO1996028717A1 (en)
ZA (1) ZA961920B (en)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19725015C2 (en) * 1997-06-13 2002-02-14 Bayer Ag Sinker for determining the rate of release of active substances
DE60316344T2 (en) * 2002-12-16 2008-06-12 N.V. Organon CONTAINER, DEVICE AND METHOD FOR TESTING THE DISSOLUTION OF PHARMACEUTICAL COMPOSITIONS
US7357046B2 (en) 2002-12-16 2008-04-15 N. V. Organon Method for dissolution testing of a pharmaceutical delivery device
TW200732644A (en) * 2005-10-25 2007-09-01 Rohm & Haas Dissolution test equipment and methods for testing having improved filtration system
DE202008014226U1 (en) 2008-10-21 2010-11-18 Levin, Felix, Dr. Test system for quick and easy analysis of substances in liquids
DE102009042345A1 (en) 2008-10-21 2010-05-12 Levin, Felix, Dr. Test system for determination of substances in e.g. urine of potentially infected patients, has test formulations provided in cup or in container and forming stable product during contact with substances in liquid in cup
CN109884281B (en) * 2019-04-12 2023-12-01 中国地质科学院岩溶地质研究所 Test device for on-line monitoring carbonate corrosion
JP7390069B1 (en) * 2022-09-20 2023-12-01 クラシエ株式会社 Drug holder, dissolution test device, and drug dissolution test method

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3862042A (en) * 1974-02-27 1975-01-21 Becton Dickinson Co Serum/plasma separator - piston with red-cell trapping surfaces
FR2546628B1 (en) * 1983-05-27 1987-02-13 Univ Bordeaux DEVICE FOR STUDYING THE RELEASE-DISSOLUTION OF MEDICINAL PRODUCTS FROM PASTY PHARMACEUTICAL FORMS
CA1274159A (en) * 1986-06-19 1990-09-18 Joseph K.S. Lee Dissolution cell and method for determining the in- vitro release of a drug
FR2655874B1 (en) * 1989-12-20 1992-03-13 Prolabo Sa SOLID DISSOLUTION CELL AND DISSOLUTION KINETICS STUDY APPARATUS COMPRISING SAME.
EP0712490B1 (en) * 1993-08-06 2002-05-29 Novartis AG Apparatus for simulating the effect of the living organism on the change in shape, the disintegration and dissolution behaviour and the active-ingredient release of a pharmaceutical dosage form

Also Published As

Publication number Publication date
BR9607230A (en) 1997-11-11
KR19980702844A (en) 1998-08-05
FI973639A (en) 1997-09-09
ZA961920B (en) 1997-09-08
IL117407A0 (en) 1996-07-23
JPH11503517A (en) 1999-03-26
MX9706805A (en) 1997-11-29
AU4885396A (en) 1996-10-02
WO1996028717A1 (en) 1996-09-19
FI973639A0 (en) 1997-09-09
GB9504893D0 (en) 1995-04-26
EP0815427A1 (en) 1998-01-07
NO974156L (en) 1997-09-09
NO974156D0 (en) 1997-09-09

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FZDE Discontinued