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
• • G—PHYSICS
  • G01—MEASURING; TESTING
  • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
  • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
  • G01N33/15—Medicinal preparations ; Physical properties thereof, e.g. dissolubility
• • 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

Definitions

• This invention relates to a dissolution testing vessel, and in particular to a vessel for testing dissolution of pharmaceutical formulations, particularly buoyant pharmaceutical formulations.
• formulations may be designed to release an initial "burst" of active ingredient followed by a steady-state release thereafter.
• 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.
• 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.
• 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 formulation will oe carried out.
• the sample is simply "dropped” into the medium and is allowed to float freely at the surface.
• the body of 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.
• 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 ingredien (s) released from the sample formulation. Th s method is described m detail by Burns et al , Int . J. Pharmaceuti cs (1995) (in press) .
• the present invention provides 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.
• the means will also prevent a formulation undergoing dissolution testing from sinking to the bottom of the testing medium.
• the invention therefore provides a testing vessel which will prevent the mechanical interaction with the means of agitation described above.
• the testing vessel of the invention is suitable for testing dissolution of both buoyant pharmaceutical formulations and sinking erodible dosage formulations.
• the means provided divide the vessel into at least two portions, while at the same time allowing the testing medium to move freely between those portions.
• the means consists of an insert, which is provided as a mesh or grille and typically will have substantially the same diameter as that of the inner wall of the vessel.
• this can be made of stainless steel.
• a particularly convenient way of allowing the insert to be held in place is to provide the vessel with one or more projections which project inwardly from the wall of the vessel and on which the insert can rest.
• a continuous projection can be provided which runs for substantially the whole of the inner circumference of the vessel, eg a collar, ridge or shoulder.
• the insert can simply be dropped into the interior of the vessel and will sit on the collar, ridge or shoulder.
• the one or more projections, or continuous projection respectively can be formed as part of the vessel itself. This s particularly the case if the vessel is made of plastic or glass.
• the pharmaceutical formulation under test will remain below the insert (if it s a floating dosage form) and will not be free to float at the surface. If, however, it is a sinking erodible dosage form, it can rest on the top of the insert. The medium itself is still agitated by means of a paddle or paddles and the normal aliquots can be taken at appropriate time points to determine the amount of active ingredient (s) released.
• the mechanical interaction between the means, for example an insert, and the formulation provides a suitable means of mechanical erosion, whether the dosage form is a floating type or sinking type, and therefore mimics the effect of the gastrointestinal tract in vivo .
• the formulation Unlike the paddle set to surface method described by Burns et al , 1995 ( supra) , there is little tendency for the formulation to stick to the means.
• Fi ⁇ ure 1 is a sectional view of a preferred embodiment of the invention.
• FIG. 1 can be seen a sectional view of a preferred vessel (1) of the invention.
• the vessel (1) is moulded with a continuous indentation(2) which runs along the entire circumference of the vessel. This effectively divides the vessel into a lower portion(3) , which represents approximately one third of the vessel's volume, and an upper portion(4) .
• the provision of the indentation means that there is also provided a shoulder or ridge (5) which runs for the whole of the internal circumference of the vessel (1) .
• An insert (6) is simply dropped into the vessel (1) and will rest upon the shoulder or ridge (5) .
• a pharmaceutical formulation undergoing testing will be placed in the vessel before 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) of the vessel (1) and will be prevented from floating freely at the surface of the testing medium by the insert (6) .
• a dissolution study was carried out with a floating dosage form, size '0' enteric-coated capsules containing a granule preparation of salmon calcitonin with a potency of 400 iu per capsule.
• the dissolution medium volume 900 ml, was maintained at 37°C ⁇ 1°C and contained 5.84 g.l" 1 disodium hydrogen orthophosphate, 4.61 g.l "1 potassium dihydrogen orthophosphate, 2.00 g.l 1 sodium cnolate and 1.00 g.l ' sodium deoxycholate adjusted to pH 6.8.
• 5 ml samples of dissolution medium were removed for analysis.
• Samples were removed at specific intervals (eg 10, 15, 20, 25 mm) , up to 30 mm, n each case the volume being replaced with fresh dissolution medium.
• the calcitonm content of the samples was determined by a specific ELISA for salmon calcitonm and quantified by comparison with authentic standards.
• the paddle rotation speed in both cases was 100 rpm.
• the values are means of 6 determinations ⁇ SD, with the coefficient of variance shown in brackets, and are expressed as percentage salmon calcitonin released from the dosage form.
• Table 1 show that the extent and rate of calcitonin . release from a floating dosage form is considerably 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 coefficient of variance.
• any suitably shaped vessel can be used, of any suitable material.
• the means provided with the vessel for preventing the pharmaceutical formulation from floating freely at the surface of the testing medium can simply be adapted to the vessel shape. All such variations are intended to be within the scope of the present invention.

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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)

Applications Claiming Priority (3)

Publications (1)

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• 1995
  • 1995-03-10 GB GBGB9504893.0A patent/GB9504893D0/en active Pending
• 1996
  • 1996-03-04 WO PCT/GB1996/000493 patent/WO1996028717A1/en not_active Application Discontinuation
  • 1996-03-04 KR KR1019970706251A patent/KR19980702844A/ko not_active Application Discontinuation
  • 1996-03-04 CA CA002214998A patent/CA2214998A1/en not_active Abandoned
  • 1996-03-04 EP EP96904938A patent/EP0815427A1/en not_active Withdrawn
  • 1996-03-04 AU AU48853/96A patent/AU4885396A/en not_active Abandoned
  • 1996-03-04 JP JP8527352A patent/JPH11503517A/ja active Pending
  • 1996-03-04 BR BR9607230A patent/BR9607230A/pt not_active Application Discontinuation
  • 1996-03-07 IL IL11740796A patent/IL117407A0/xx unknown
  • 1996-03-08 ZA ZA9601920A patent/ZA961920B/xx unknown
• 1997
  • 1997-09-09 FI FI973639A patent/FI973639A0/fi not_active Application Discontinuation
  • 1997-09-09 NO NO974156A patent/NO974156L/no unknown

Non-Patent Citations (1)

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