GB2583468A - A device for measuring tablet and granule dissolution and disintegration - Google Patents
A device for measuring tablet and granule dissolution and disintegration Download PDFInfo
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- GB2583468A GB2583468A GB1905668.8A GB201905668A GB2583468A GB 2583468 A GB2583468 A GB 2583468A GB 201905668 A GB201905668 A GB 201905668A GB 2583468 A GB2583468 A GB 2583468A
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- 239000008187 granular material Substances 0.000 title claims abstract description 105
- 238000004090 dissolution Methods 0.000 title claims abstract description 50
- 239000004480 active ingredient Substances 0.000 claims abstract description 21
- 238000004128 high performance liquid chromatography Methods 0.000 claims abstract description 7
- 238000005406 washing Methods 0.000 claims abstract description 6
- 239000000843 powder Substances 0.000 claims abstract description 5
- 239000003814 drug Substances 0.000 claims description 15
- 229940079593 drug Drugs 0.000 claims description 7
- 239000007921 spray Substances 0.000 claims description 4
- 238000005469 granulation Methods 0.000 claims description 3
- 230000003179 granulation Effects 0.000 claims description 3
- 238000009476 low shear granulation Methods 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- 238000009477 fluid bed granulation Methods 0.000 claims description 2
- 238000009478 high shear granulation Methods 0.000 claims description 2
- 239000004615 ingredient Substances 0.000 claims description 2
- 238000000917 particle-image velocimetry Methods 0.000 abstract 2
- 229940126601 medicinal product Drugs 0.000 abstract 1
- 239000000825 pharmaceutical preparation Substances 0.000 abstract 1
- 229940127557 pharmaceutical product Drugs 0.000 abstract 1
- 239000011230 binding agent Substances 0.000 description 17
- 238000010586 diagram Methods 0.000 description 14
- 239000012530 fluid Substances 0.000 description 14
- 238000012546 transfer Methods 0.000 description 14
- 239000007787 solid Substances 0.000 description 13
- 239000000523 sample Substances 0.000 description 10
- 238000000034 method Methods 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 239000002245 particle Substances 0.000 description 8
- 229920005439 Perspex® Polymers 0.000 description 5
- 239000004926 polymethyl methacrylate Substances 0.000 description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 230000007704 transition Effects 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 3
- 239000011148 porous material Substances 0.000 description 3
- 239000011164 primary particle Substances 0.000 description 3
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 229930003268 Vitamin C Natural products 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- 235000019154 vitamin C Nutrition 0.000 description 2
- 239000011718 vitamin C Substances 0.000 description 2
- 206010007556 Cardiac failure acute Diseases 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000002902 bimodal effect Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- -1 e.g. Substances 0.000 description 1
- 230000003628 erosive effect Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000001360 synchronised effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
-
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
- G01N21/33—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using ultraviolet light
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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)
- Chemical Kinetics & Catalysis (AREA)
- Electrochemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
To determine the granule and tablet dissolution and disintegration profile a device preferably comprising a flow cell may be used with active ingredient measuring equipment. Preferably the active ingredient measuring equipment comprises a conductivity meter, an ultraviolet analyser or high performance liquid chromatography (HPLC). The device may be further combined with a high-speed video camera or laser particle image velocimetry (PIV). Preferably the granules or tablets comprise washing powder, medicinal/pharmaceutical products, food or coffee granules. The granule or tablet size preferably falls within the range 20μm to 50mm, or 50μm to 20mm.
Description
A device for measuring tablet and granule dissolution and disintegration
HELD OF THE INVENTION
This invention relates to a device for determining tablet and/or granule dissolution and disintegration profile, more particularly, this invention relates to a device for measuring the release of active ingredients from tablet and/or granules in order for the optimisation of product performance.
BACKGROUND OF THE INVENTION
Tablet and granule dissolution and disintegration (TGDD) are of significant interest to both science and industry. In industry, increasing use of tablet and granular materials in the chemical, petrochemical, food and pharmaceutical industries, both as intermediate and end products, e.g., medicines and detergents, gives rise to the need for a better understanding of tablet and granule dissolution and disintegration. A good knowledge of the physical principles which control the release of active ingredients from tablet and/or granule is crucial for the optimisation of product performance.
It has been noticed that the bio-availability, a term commonly used in medical science to describe the effectiveness of the absorption of a medicine by human body, depends on their dissolution rate and mechanism. Take a vitamin C tablet as an example; it has been shown that tablet with a mean disintegration time of 60 minutes has the highest bio-availability. A shortened or lengthened disintegration time reduces the bio-availability, hence reducing the vitamin C absorption in a body. Thus, in the pharmaceutical industry, controlled release is paramount, although in most cases fast dissolution is also essential, such as medicine drug used to treat acute heart failure. Researchers are trying to improve the disintegration ability of drug tablets by the selection of binders. Another example is washing powder. The need to gain a better understanding of granule dissolution and disintegration is driven by the constant demand of consumers for better products. Therefore, an understanding of TGDD is of direct technological importance.
Dissolution refers to the process by which a solid dissolves into a continuous solvent phase, i.e. the transfer of mass from the soluble solute into the solvent. However, tablet and granule dissolution and disintegration (TODD) is more specific. A heterogeneous aggregate is composed of insoluble or sparingly soluble solid particles and a soluble binder, e.g., a drug granule used to forming tablet contains soluble lactose and one or a few different sparingly soluble active ingredients. TGDD refers to the process by which granules disintegrate in a solvent, resulting in binder dissolution and the liberation of insoluble primary particles. TGDD is different from the dissolution of a homogeneous material, a simple molecule dissolution, where the process proceeds at a rate largely governed by the chemistry of the components. TGDD is more complicated because the heterogeneous system involves the mix of insoluble particles and a soluble binder or different dissolution rates of sparingly soluble particles. In addition, the influences of various physical properties such as granule size, the primary particle, binder-solid ratio, and internal pore structure further complicate TGDD behaviour. Therefore, in the case of TGDD, the physical properties of the granule should be taken into consideration. In the case of TGDD, there is greater interest in how individual particles of granules break up or disintegrate rather than in how the individual molecule dissolves into the solvent. It is expected that when primary particles detach from a granule, or solvent diffuses inside the granule, fresh particles will be exposed to the solvent, and thus the apparent dissolution rate may change. In addition, the overall dissolution mechanism may vary. In general, the major difference between molecule dissolution and TGDD is that the latter requires information on the tablet and/or granule structure, thus formulation of the dissolution model must take into consideration the granule structure. One of practical example in medicine application is how the active ingredient of a drug granule releases by the disintegration and dissolution process hence influencing bioavailability.
In TGDD, to monitor insoluble particle or binder alone cannot give a complete image of how granule dissolution and disintegration take place. It is possible that dissolution and disintegration may not be synchronous, i.e., particles and binder transport rates differ.
It is therefore the aim of the present invention to provide a device for determining granule dissolution and disintegration profile, more particularly, measuring the release of active ingredients from granules in order for the optimisation of product performance.
BR!EF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAVVINGS An example of the invention will now be described by referring to the accompanying drawings: Figure 1: is a diagram showing microscope flow cell.
Figure 2: is a diagram showing a) tube fitted for conductivity probe, b) conductivity probe which is used to plug in tube in figure 2a) Figure 3: is a diagram showing conceptualised flow cell apparatus (note: conductivity could be replaced by other active ingredient testing equipment, such as UV analyser or HPLC or any other system could be used measure concentration of ingredients) Figure 4: is a diagram showing a typical granule dissolves in flow cell, a) t = 0; b) t= 50 s (flow rate of 0.008 m s-1) Figure 5: is a diagram showing granules made by high shear granulation dissolution profile, a) diameter variation versus time; b) conductivity variation versus time.
Figure 6: is a diagram showing granules made by low shear granulation dissolution profile; a) diameter variation versus time, b) conductivity variation versus time.
Figure 7: is a diagram showing granule mass transfer coefficient variation versus time (low shear granule 800 gm) under different flow rate; a) Solid mass transfer coefficients kc versus time. b) Binder mass transfer coefficients versus time.
Figure 8; is a diagram showing Comparison of TGDD kc kcB: a) kc versus Reynolds number, b) ke versus Reynolds number (LS granule 800 jim).
Figure 9: is a diagram showing solid Sherwood number analysis which suggests a different trend, i.e. not being limited by solid transport due to normalised solid Sherwood number being far below the Frossling equation predicted value.
Figure 10: is a diagram showing a spray dried granule after 50 s of dissolution time (flow rate of 0.008 m s-1) DESCRIP.11014
Brief description of the invention
This invention designed a special piece of equipment, the microscope flow cell, combined with active ingredient measuring equipment, such as conductivity meter or UV analyser, or HPLC, in order to give an explicit and complete image of how the dissolution and disintegration of a granule take place, as well as determining which one is the dominating factor under controlled hydrodynamic conditions. The microscope could also be replaced by high speed video camera or laser PIV.
Detailed description of the invention Summary of the invention The object of the present invention is to provide a device for measuring the dissolution and disintegration of tablet and/or granules, the device comprising; * a square channel flow cell made of Perspex and two microscope slides or transparent cover such as glass, Figure 1; * a cylindrical tube made of Perspex to connect the exit of square channel and fix the electrical conductivity probe, Figure 2 a); * an electrical conductivity probe was fitted in the cylindrical container and sealed with rubber o-rings, Figure 2 b).
The above pieces of components are connected with a flow system, Figure 3. The square flow cell is placed under microscope or any type of monitor to record the size change of tablet or granule, such as video camera. The mentioned electrical conductivity probe could be replaced by other detecting method, e.g., UV analyser or high performance liquid chromatography (HPLC) to measure the active ingredient released in the TGDD process.
Flow cell design To see clearly what happen under the microscope, a square channel flow cell, made of Perspex and two microscope slides, was designed. The square channel was sealed between the two microscope slides, similar to a sandwich (See Figure 1. Two principles were followed in designing the microscope flow cell.
1. The flow rate must be well defined, i.e. fixed flow rate.
2. The flow condition must be stable.
The velocity distribution in the laminar flow will form a parabolic velocity distribution because of the fluid viscosity. The original analysis for laminar flow is developed by Hagen and Poiseuille, used to describe flow through a circular tube. Bird et al. gave an equation based on momentum transport to describe laminar flow in a narrow slit.
V = X w(To 'Pt* c 2 2 \ 24),p B (1) where xcw is the distance from centre to the point of measured velocity, BC is the channel half width, p is the fluid viscosity, Lfp is the distance fluid passed, Jb9'i, is the pressure difference for fluid passing distance Li. An average velocity is given by: -3 vm (2) where Q is the volumetric flow rate, and AC is the cross-sectional area of the channel. The velocity distribution in a square channel has the similar form as that one in a circular tube, which has form as follow. (3) (4)
v = (To -(1; )R2 (v) = 1 2 * where R is the radius of the circular tube. As granule has spherical shape, for the convenience to make decision how wide the channel should be taken, the average velocity in the middle regime covering granule area is estimated as follow.
1rG vrdrc18 0 r2R rrG "max jo rdrch9 1 4L [ 2g (To -p r 1 2 (To-(PL)R2 1 r 2 2 R (5) where rG is the radius covering granule project area. According to Equation 5, for a 1 mm granule, if the width of channel is 5 mm, the average velocity cross the granule area has ( 1--Gvaa1 = 0.98v 2 5-gar2 R2 r 1 11v (6) Therefore a channel of 5 mm width is sufficient to provide uniform velocity across the granule area. Even for a granule of 2 mm size, the average velocity cross the granule area has 92% maximum velocity. This estimation is effect for square channel as both has the similar form of velocity distribution. The average velocity of square channel is more close to the maximum velocity (see Equations 4 and 6). The fact, the uniform velocity around granule area, also eliminates the concern of the Sherwood number approximation affected by the wall effect.
To have the above velocity distribution as well as obtain a steady-state fluid rate it was necessary to maintain a fully developed flow passing the granule. Thus, the entrance length should be considered to make sure the dissolution takes place in a steady fluid.
For the laminar flow condition, Bird et al. gave: LQ = 0.035D1, Re (7) where Dp is the diameter of the pipe, Re is the Reynolds number, and Le is the entrance length which is required for build-up of fully developed parabolic profiles. Equation 7 is developed for circular tube. For square channel, there is no direct reference regarding entrance length available. However, in hydrodynamics, it is often using hydraulic radius, Rh, as conduits do not always have circular cross sections. Hydraulic radius is valid approach because the shear stress occurring at the wall will be the same for a given fluid average velocity regardless of conduit shape. The hydraulic radius, Rh, is defined as by Griskey: RCross -sectional area perpendicular to flow
-
Wetted perimeter (8) This concept leads to that there is an equivalent or hydraulic diameter, Deq/Dh, for any cross section such that Dec, = Dn = 4R, (9) As square channel is very close to circular tube, therefore this approach should be sufficient to calculate the entrance length. For a square channel of 5 mm width, the hydraulic diameter equals 5 mm according to Equations 8 and 9. For a maximum velocity of 0.03 m s-1 at centre of the channel used in this work, the average velocity is 0.02 m s-1 according Equation 9. Therefore Reynolds number of the channel has Re "mme, = - =100fi 0.00 lkg s D "up 0.005m x 0.02ms-1 x1000kgm-3 (io) Therefore the entrance length Le = 0.035x 5 10-3 x 100 = 17.5 mm As the microscope slide length was 76 mm, it was sufficient to satisfy the requirement for an entrance length for the channel. To further assure the fluid fully developed, the tube connected to the square has the close cross section area. As parabolic velocity distribution has been well established for both large and small scale from hydrodynamic theory to practice, it is reasonable to have the approximation value of fluid velocity for the designed channel. The Perspex channel is shown in Figure 1.
For measuring the real time binder concentration, a special tube was designed to connect the exit of square channel and fix the electrical conductivity probe (see Figure 2 a) and b). A cylindrical container was made of Perspex (see Figure 2 a). The electrical conductivity probe (see Figure 2b) was fitted in the cylindrical container and sealed with rubber o-rings. Two orifices were made as shown in Figure 2a. The dissolved solution fluid was pumped from the low orifice, passed through the conductivity probe, flowed out of the orifice of the probe, and finally out of the container via high orifice on the tube. The conductivity value was read when the fluid passing the electrode. Because there was no solution accumulation for this specially designed tube, the measured binder release rate reflects the in situ binder release rate for a single granule.
Solvent distilled water was supplied from a large tank, with the flow rate being controlled by a screw clip. Flow rates were calibrated by measuring the flow volume at a known time. Figure 4 is a schematic diagram of the flow cell experiment equipment. Solvent fluid enter the micro flow cell, pass and dissolve the granule, then pass through the conductivity probe. The pinned granule was put in the position 20 mm close to the flow cell exit. The length of the needle is 30 mm with a spring end to hold in the tube. This provides further sufficient distance for fluid fully developed. In the same time the distance of 20 mm from the granule to the exit of the flow cell is also sufficient to leave fluid uninterrupted to the region of granule.
A typical Results analysis of granules dissolution and disintegration profile Figure 5 describes the TGDD of HS granules with initial starting size of 700 gm under various flow rates. Figures 6a and 6b show the change in diameter and the conductivity profile as a function of time, respectively. It can be seen that both the diameter and the conductivity decays with time but the trend is slightly different. The diameter profile shows a convex shape while the conductivity profile shows a concave shape_ It is shown that high flow rate results in shorter dissolution time The data are analysed as follows.
Firstly, the diameter profile was modelled and the solid mass transfer coefficient kc was calculated. The experimental diameter profile data were fitted by the use of the bimodal population model deduced according to the following equation.
1 2ku 14\ 1-m
-Do Do (12)
The solid line in Figure 6a shows the modelled diameter profile. It can be seen that the experimental data can be well described by the equation.
From the modelling, the solid mass transfer coefficient, kcO, and the exponential index, In, can be extracted. For Figure 6a, kco and in were calculated as 2.2 gm s-1 and -0.5 for flow rates of 0.031 m s-1; 1.5 pm s-1 and -0.5 for flow rates of 0.020 m s-1; and 0.55 pm s-1 and -0.5 for flow rates of 0.008 m s-1, respectively. Hence, the solid mass transfer coefficients can be calculated based on Equation (13). II!
7 \ 2k° (1-in)tAm= k° 1 D1) ( 13) Discussion Figures 7 to 10 show the dissolution of different granules under the microscope flow cell. During the experiments, two prominent phenomena were observed: Granules did not disintegrate into large fragments despite the difference in porosities. The dissolution is a surface process.
Granules containing more pores produced more bubbles than those containing less pores.
Observation 1 does not claim that granule disintegration did not happen at all, as the disintegration of small aggregates (less than 20 Im) was not included. Indeed in rare incidents, some granules did break, which is difficult to describe quantitatively. However, the majority of the granules followed the surface erosion process, i.e., no disintegration occurred. Small aggregates less than 20 pm are difficult to see at the same magnification scale as that used for the granule image under the microscope. It is therefore difficult to claim that disintegration did not happen at this level. However, this would not affect the conclusion that majority of TGDD occurs as a surface process above the 20 p.m scale level.
EXEMPLARY EMBODIMENTS
In accordance with one embodiment of the present invention, a granule of washing powder dissolution and disintegration profile is monitored by the this invention, the microscope flow cell, combined with active ingredient measuring equipment conductivity meter In another embodiment, a medicine thug granule made of lactose excipients and active ingredient dissolution and disintegration profile is monitored by the this invention, the microscope flow cell, combined with active ingredient measuring equipment UV analyser In a further embodiment, a medicine drug tablet made of two different excipients and two different active ingredients dissolution and disintegration profile is monitored by the this invention, the microscope flow cell, combined with active ingredient measuring equipment HPLC The above is just some example, the system can be used for granules made by various granulation, namely high shear granule, low shear granulation, fluidised bed granulation, spray dried granulation. The lists are not limited here. The system can be used for washing powder, washing tablets, medicine granule, medicine tablets and all granules tablets applied in chemical and pharmaceutical industries.
EXAMPLE Example 1
Figure 4 shows a typical dissolution profile of a HS granule. Figure 4a shows the granule starting to dissolve at initial time, t = 0. Figure 4b shows the same granule after 50 s of dissolution, t = 50 s. It can be seen that only two bubbles appeared on the granule surface after GDD processed 50 s, which is consistent with low porosity of this type of granule. From the figure, granule diameter was obtained by calculating the projected area of the granule. One of the typical results of granule diameter versus time at different flow rates, is shown in Figure 5 a). At the same time, the conductivity profile was recorded, to monitor binder dissolution behaviour, which is also shown in Figure 5b).
Figure 4 describes a typical TGDD profile of HS granules of 750 gm under various flow rates. Figures 5a and 5b describe granule diameter and conductivity profile as a function of time, respectively. It is clear that a higher flow rate results in a shorter dissolution time. It can be seen that granule diameter and conductivity, decay with the progress of the TGDD with different-shaped curves. Granule diameter shows a convex shape while conductivity shows a concave shape with the progress of the TGDD. The different behaviour of granule diameter and conductivity profiles origin from the different transport abilities of particles and binder, as well as the reaction behaviour between binder and solvent.
Example 2
Figure 6 shows a typical dissolution profile of an LS granule. Similar to the examination of HS granules, granule diameter and the conductivity of the solution profiles were monitored, a) diameter variation versus time, b) conductivity variation versus time.
Example 3
Figure 7 shows a typical dissolution image of an FB granule. Figure 7 is a diagram showing granule mass transfer coefficient variation versus time (FB granule 800 ftm) under different flow rate; a) Solid mass transfer coefficients kc versus time. b) Binder mass transfer coefficients versus time.
It can be seen that initial binder mass transfer coefficients are higher than solid mass transfer coefficients. A transition for binder mass transfer coefficient exists as TGDD progresses for both flow rates of 0.020 and 0.031 m s-1. Binder mass transfer coefficients decrease with the decrease of the Reynolds number initially and increase after passing the transition point. The reason for the extended transition point for the 0.020 m s-1 flow rate is most probably due to a higher porosity granule. With the increase in porosity, the solid shell is more quickly built up and consumed, and hence the transition point appears.
Example 4
Example 4 in Figure 8 is a diagram showing Comparison of TGDD kc kcB; a) kc versus Reynolds number, b) kc'' versus Reynolds number (LS granule 800 Um).
Example 5
Figure 10 shows a typical dissolution image of a SD granule. Figure 10 is a diagram showing a spray dried granule after 50 s of dissolution time (flow rate of 0.008 m s-1). It can be seen that more bubbles appeared on the granule surface due to higher porosity of this type of granule, when compared to other type of granules.
Claims (11)
- CLAWSThis invention relates to a device for determining granule dissolution and disintegration profile, more particularly, this invention relates to a device for measuring the release of active ingredients from granules in order for the optimisation of product performance.1. A device for determining granule and tablet dissolution and disintegration profile, more particularly, for measuring the release of active ingredients from granules in order for the optimisation of product performance.
- 2. A device according to claim 1, are made of the microscope flow cell, combined with active ingredient measuring equipment, such as conductivity meter
- 3. A device according to claim 1, are made of the microscope flow cell, combined with active ingredient measuring equipment, such as UV analyser
- 4. A device according to claim 1, are made of the microscope flow cell, combined with active ingredient measuring equipment, such as HPLC
- 5. A device according to claim 1, are made of the microscope flow cell, combined with high speed video camera or laser PIV or alike and active ingredient measuring equipment, such as conductivity meter, UV analyser, HPLC and alike
- 6. A device according to claim 1-5 can measure granule or tablet image evolution and ingredient release concentration simultaneously and give an explicit and complete image of how the dissolution and disintegration of a granule take place, as well as determining which one is the dominating factor under controlled hydrodynamic conditions.
- 7. A device according to claim 1-6 can determine granule or table dissolution and disintegration profile of chemical industry product such as washing powder
- 8. A device according to claim 1-6 can determine granule or table dissolution and disintegration profile of pharmaceutical industry product such as medicine drug
- 9. A device according to claim 1-6 can determine granule or table dissolution and disintegration profile of any other industry product such as food industry, coffee granule or petrochemical industry or any alike.
- 10.A device according to claim 7-9, granules and tablet can be made by various prior art technology, such as high shear granulation, low shear granulation, fluidised bed granulation, spray dried granulation, tablet machine, and alike.
- 11.A device according to claim 7-9, granule and tablet size can be from 20 p.m to 50 mm, preferably 50 pm to 20 mm.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB1905668.8A GB2583468A (en) | 2019-04-23 | 2019-04-23 | A device for measuring tablet and granule dissolution and disintegration |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB1905668.8A GB2583468A (en) | 2019-04-23 | 2019-04-23 | A device for measuring tablet and granule dissolution and disintegration |
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| GB201905668D0 GB201905668D0 (en) | 2019-06-05 |
| GB2583468A true GB2583468A (en) | 2020-11-04 |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4108602A (en) * | 1976-10-20 | 1978-08-22 | Hanson Research Corporation | Sample changing chemical analysis method and apparatus |
| US20030086823A1 (en) * | 2001-11-07 | 2003-05-08 | Fernando C J Anthony | Fiber-optic dissolution systems, devices, and methods |
| EP2402748A1 (en) * | 2010-06-30 | 2012-01-04 | Rohm and Haas Company | Delivery device for dispensing pharmaceutical dosage forms into dissolution testing apparatus |
| WO2014027323A1 (en) * | 2012-08-14 | 2014-02-20 | Fondazione Istituto Italiano Di Tecnologia | Device and method for determining the dissolution kinetics of colloidal nanoparticles |
| US20190101518A1 (en) * | 2017-10-28 | 2019-04-04 | Royan Institute | Dissolution test for sensitive drugs |
-
2019
- 2019-04-23 GB GB1905668.8A patent/GB2583468A/en not_active Withdrawn
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4108602A (en) * | 1976-10-20 | 1978-08-22 | Hanson Research Corporation | Sample changing chemical analysis method and apparatus |
| US20030086823A1 (en) * | 2001-11-07 | 2003-05-08 | Fernando C J Anthony | Fiber-optic dissolution systems, devices, and methods |
| EP2402748A1 (en) * | 2010-06-30 | 2012-01-04 | Rohm and Haas Company | Delivery device for dispensing pharmaceutical dosage forms into dissolution testing apparatus |
| WO2014027323A1 (en) * | 2012-08-14 | 2014-02-20 | Fondazione Istituto Italiano Di Tecnologia | Device and method for determining the dissolution kinetics of colloidal nanoparticles |
| US20190101518A1 (en) * | 2017-10-28 | 2019-04-04 | Royan Institute | Dissolution test for sensitive drugs |
Also Published As
| Publication number | Publication date |
|---|---|
| GB201905668D0 (en) | 2019-06-05 |
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