FIELD OF THE INVENTION

The invention relates to a device for testing the Equilibrium Relative Humidity (ERH) of a test sample and a corresponding method.

BACKGROUND OF THE INVENTION ERH is the % relative humidity (RH) of the air surrounding a material at the equilibrium point of moisture absorption/desorption. ERH is also known and measured as Water Activity (A _w ). ERH measurement has only recently been used in the pharmaceutical industry and other similarly regulated industries in order to assess the moisture status and stability of active ingredients/end formulations under ambient and different test conditions, for example during manufacture, after storage etc.

An ERH measurement is derived from relative humidity (%RH) data. Hygrometers are conventionally used to measure %RH. There are many different types of hygrometer available on the market. As shown in Figure 1 , known methods for %RH and hence ERH measurement generally involve placing a test sample in a closed container 3 provided with a temperature/humidity sensor 5. One such device is described in the applicant's GB 2487186 A. There has to be a known set %RH in the container before the measurement takes place. However, the container has to be opened in order to introduce a sample into the container and closed again after the sample has been located in the container. This operation alters the %RH in the container. Therefore, test results are likely to be compromised. Thus, there is a need to provide an improved system to measure the ERH of test samples.

The object of the present invention is to obviate and mitigate the above drawback(s).

SUMMARY OF THE INVENTION

According to a first aspect of the present invention, there is provided a device for measuring the ERH of a sample of pharmaceutical material, the device comprising:

a first container defining an enclosed test chamber for receiving the sample; a relative humidity (%RH) sensor and a means for recording the ERH in communication with the test chamber; and

a humidity adjusting device arranged in communication with the first container to adjust %RH in the test chamber.

In one arrangement, the humidity adjusting device comprises a source of moisture vapour.

In one arrangement, the first container includes an inlet port arranged in communication with the humidity adjusting device; and the inlet port is operable between an open state in which moisture vapour is allowed to access or leave the test chamber and a closed state in which the moisture vapour is prevented from accessing or leaving the test chamber. Preferably, the first container and the humidity adjusting device are located within a sealed enclosure structure.

In one arrangement, the first container has an open end for receiving the sample therethrough; and a closure member placeable over the open end of the first container for closing and sealing the open end.

In one arrangement, the open end of the first container is located on an external side of the enclosure structure to allow the sample to be placed into the test chamber from outside the enclosure structure. Preferably, the first container is sealingly connected with the enclosure structure around the open end of the first container. In this way, access into the test chamber from outside the enclosure structure is only allowed though the open end of the first container.

In one arrangement, the humidity adjusting device includes an outlet port operable between an open state in which moisture vapour is allowed to egress or access the humidity adjusting device and a closed state in which the moisture vapour is prevented from egressing or accessing the humidity adjusting device.

The moisture vapour can be provided in the humidity adjusting device by any suitable method apparent to a person skilled in the art. For example only, a heating element and a volume of liquid may be provided in the humidity adjusting device wherein on activation of the heating element liquid begins to evaporate; or a volume of liquid alone can provide moisture vapour through unaided evaporation. Alternatively, damp or wet salt can be provided as a source of moisture vapour. It will be appreciated that the humidity adjusting device may also be operable to remove moisture from the test chamber and its surroundings in order to establish the required %RH in the test chamber. In this variation, salt can act as a moisture absorbing substance. Preferably, the inlet port of the first container and the outlet port of the humidity adjusting device are located within the sealed enclosure structure.

In one arrangement, the %RH sensor is provided in the enclosure structure, preferably adjacent the first container. A further %RH sensor may be provided within the test chamber.

Preferably, the device includes a control means for controlling the operation of the device. The control means may be adapted to control the opening/closure of the inlet port of the first container and, if applicable, the outlet port of the humidity adjusting device. The control means may include an electrical or an electromechanical actuator. The control means may include an electronic control module for controlling the opening/closure of the or each port. The electronic control module preferably includes a programmable electronic processor. A number of ways to provide a control means would be apparent to a person skilled in the art.

In one arrangement, in order to test the ERH of a sample, the sample is placed into the test chamber and humidity adjusting device is activated to establish a predetermined %RH outside the test chamber. Once the predetermined %RH is reached, the test chamber and the humidity adjusting device are allowed to communicate to establish humidity equilibrium therebetween. Once humidity equilibrium has been established, the ERH of the sample is recorded. The sample is preferably placed into the test chamber through the open end of the first container and the closure member is placed over the open end to sealingly close the open end of the first container. In the arrangement comprising the sealed enclosure structure and the humidity adjusting device including the outlet port, in order to test the ERH of a sample, the control means is configured to control opening/closure of the inlet port of the first container and the outlet port of the source of moisture such that: after the sample has been placed into the test chamber, the inlet port of the first container initially remains closed while the outlet port of the humidity adjusting device is opened to establish a predetermined %RH in the enclosure structure; once the predetermined %RH is reached in the enclosure structure, the outlet port of the humidity adjusting device is closed and the inlet port of the first container is opened so that moisture vapour is allowed to migrate between the enclosure structure and the test chamber; and once humidity equilibrium has been reached in the enclosure structure and in the test chamber, the inlet port is closed and the ERH of the sample is recorded. In one arrangement, the inlet port of the first container is provided by two or more portions of the first container arranged to move relative to each other wherein in a first position a gap is defined between the two portions and moisture vapour is allowed to access or leave the test chamber and in a second position the gap is closed and the moisture vapour is prevented from accessing or leaving the test chamber. The two or more portions of the first container may comprise telescopic tubular portions.

In one arrangement, the humidity adjusting device may be provided in the form of a second container defining a moisture chamber. The second container may include an open end for receiving a source of moisture or a moisture absorbing means therethrough. The second container may include a closure member placeable over the open end of the second container for closing and sealing the open end. The open end of the second container may be located on an external side of the enclosure structure to allow moist matter or moisture absorbing means to be placed into the second container from outside the enclosure structure. The second container may be sealingly connected with the enclosure structure around the open end of the second container. In this way, access into the second container from outside the enclosure structure is only allowed though the open end of the second container. The outlet port of the second container may be provided by two or more portions of the second container arranged to move relative to each other wherein in a first position a gap is defined between the two portions and moisture vapour is allowed to egress or access the second container and in a second position the gap is closed and the moisture vapour is prevented from egressing or accessing the second container. The two or more portions of the second container may comprise telescopic tubular portions. Other ways of implementing the humidity adjusting device in the enclosure are possible as will be appreciated by a person skilled in the art.

Preferably, the or each %RH sensor is also operable to test temperature.

The device of the present invention is particularly suitable for testing and characterising pharmaceutical materials. The pharmaceutical material may be in any suitable form. For example, the pharmaceutical material may be a one piece object, such as, for example, a tablet or a capsule. The pharmaceutical material may also be in the form of a flowable substance, such as a powder or viscous liquid, for example, a gel, cream or lotion. Preferably, the or each %RH sensor serves as the means for recording the

ERH.

The closure member for closing and sealing the open end of the first container and, if applicable, the second container, may comprise a cap which may be, for example, a screw cap or a plug.

It will be appreciated that the first container, the second container and the enclosure structure may be of any suitable shape as long as the shapes allow the enclosure structure to accommodate therein the first container and the second container.

The first container and, if applicable, the second container, may be made of any suitable material including metal, glass or plastic, such as High Density Polyethylene (HDPE) or laminated materials, wherein same or different materials may be laminated. For example only, a plastic container may be coated with a layer of metal or other suitable moisture barrier material to enhance its moisture impermeability.

The material to be tested may be a drug active substance, other powder or a mixture/formulation thereof, cosmetic, agrochemical, herbal, excipient or other pharmaceutical material.

According to a second aspect of the present invention, there is provided a method of measuring the ERH of a sample of pharmaceutical material, the method comprising the steps of:

a) providing a device comprising

a first container defining an enclosed test chamber for receiving the sample;

a relative humidity (%RH) sensor and a means for recording the ERH in communication with the test chamber; and

a humidity adjusting device arranged in communication with the first container to adjust %RH in the test chamber;

b) placing the sample into the test chamber;

c) activating the humidity adjusting device to adjust %RH in the test chamber; d) measuring the %RH and recording the ERH of the sample.

The method may include the step of locating the first container and the humidity adjusting device within a sealed enclosure structure.

In one arrangement, the first container has an open end for receiving the sample therethrough; and the method may include the step of placing the sample into the test chamber through the open end and placing a closure member over the open end of the first container to close and seal the open end.

In one arrangement, the open end of the first container is located on an external side of the enclosure structure and the method includes placing the sample into the test chamber through the open end from outside the enclosure structure.

In one arrangement, the method includes the step of activating the humidity adjusting device to establish a predetermined %RH outside the test chamber and once the predetermined %RH is reached, allowing the test chamber and the humidity adjusting device to communicate to establish humidity equilibrium therebetween; and once humidity equilibrium has been established, recording the ERH of the sample.

In one arrangement, the first container includes an inlet port arranged in communication with the humidity adjusting device and the method includes the step of opening the inlet port prior to, simultaneously with or after the step c), to allow moisture vapour to access or leave the test chamber.

In one arrangement, the humidity adjusting device includes an outlet port and the step c) includes opening the outlet port to allow moisture vapour to egress or access the humidity adjusting device and once the predetermined %RH has been reached, closing the outlet port to prevent the moisture vapour from egressing or accessing the humidity adjusting device.

Preferably, the inlet port of the first container and the outlet port of the humidity adjusting device are located within the sealed enclosure structure and the method includes the steps of:

after placing the sample into the test chamber, opening the outlet port of the humidity adjusting device to establish the predetermined %RH therein while keeping the inlet port of the first container closed;

once the predetermined %RH is reached in the enclosure structure, closing the outlet port of the humidity adjusting device and opening the inlet port of the first container so that moisture vapour is allowed to migrate between the enclosure structure and the test chamber;

once humidity equilibrium has been reached in the enclosure structure and in the test chamber, closing the inlet port, measuring the %RH and recording the ERH of the sample.

In one arrangement, the humidity adjusting device may be provided in the form of a second container defining a moisture chamber. The second container may include an open end for receiving a source of moisture or a moisture absorbing means therethrough; and the method may include the step of delivering moist matter or a moisture absorbing means into the moisture chamber through the open end and placing a closure member over the open end of the second container to close and seal the open end.

The open end of the second container may be located on an external side of the enclosure structure and the method includes placing the moist matter or the moisture absorbing means into the second container through the open end from outside the enclosure structure.

The present invention provides an advantage over existing devices in that it allows a pre-determined starting %RH to be controlled and provides an arrangement for setting up a sample for testing and keeping it isolated within the test chamber until the starting %RH has been established within the test chamber. Once achieved, the %RH is maintained until the test chamber is opened. At that point, the %RH will change until humidity equilibrium is established with the interior of test chamber, including the sample. The change in %RH is recorded prior to and including the point of ERH. At this point several readings of similar value of %RH will be made until the test is terminated.

As a result, accuracy and precision of the test result is increased. This is achieved in the present invention by sealing the container of the device after the interior of the test chamber has been exposed to the surrounding atmosphere and bringing the %RH within the chamber to the level necessary for conducting the test and maintaining the %RH at that level during the test. This has not been possible heretofore with the existing devices. Furthermore, the present invention provides a portable, self-contained device which, unlike some known systems, does not require complicated stationary connections, such as, for example, manifolds or cables, thereby rendering the device very easy to manipulate and transport.

All essential, preferred or optional features or steps of the first aspect of the invention can be provided in conjunction with the features of the second aspect of the invention, and vice versa, as appropriate.

BRIEF DESCRIPTION OF THE DRAWINGS

Embodiments of the present invention are described hereinafter with reference to the accompanying drawings in which:

Figure 1 is a schematic side view of a prior art device for ERH measurement; Figure 2 is a schematic side view of a device for ERH measurement in accordance with the invention in a first state; and

Figure 3 is a schematic side view of the device of Figure 2 in a second state. DETAILED DESCRIPTION OF THE INVENTION

Referring to Figures 2 and 3, an embodiment of a device for and method of ERH measurement in accordance with the invention will now be jointly described. The device of the invention is indicated generally by reference numeral 7. The device 7 comprises a first container 9 defining an enclosed test chamber (not indicated by a numeral) for receiving a sample (not shown). The device 7 comprises a humidity adjusting device 1 1 which may be arranged to release or absorb moisture vapour. The first container 9 includes an inlet port 15 arranged in communication with the humidity adjusting device 1 1 as will be described in more detail below. The inlet port 15 is operable between an open state (Figure 3) in which moisture vapour is allowed to access or leave the test chamber and a closed state (Figure 2) in which the moisture vapour is prevented from accessing or leaving the test chamber.

The first container 9 and the humidity adjusting device 1 1 are located within a sealed enclosure structure 17. A relative humidity (%RH) sensor 27 and a means for recording the ERH (not shown) are located within the enclosure structure 17. The %RH sensor may also serve as the means for recording the ERH. Preferably, the %RH sensor is also operable to test temperature.

The first container 9 has an open end 19 (shown closed in the drawings) for receiving the sample therethrough and a closure member 21 , provided in the presently described embodiment in the form of a cap, which may be, for example, a screw cap or a plug, placeable over the open end 19 of the first container 9 for closing and sealing the open end 19.

The open end 19 of the first container 9 is located on an external side 23 of the enclosure structure 17 to allow the sample to be placed into the test chamber from outside the enclosure structure 17. The first container 9 is sealingly connected with the enclosure structure 17 around the open end 19 of the first container 9. In this way, access into the test chamber from outside the enclosure structure 17 is only allowed though the open end 19 of the first container 9.

The humidity adjusting device 1 1 includes an outlet port 25 operable between an open state (Figure 2) in which moisture vapour is allowed to egress or access the humidity adjusting device 1 1 and a closed state (Figure 3) in which the moisture vapour is prevented from egressing or accessing the humidity adjusting device 1 1 .

The moisture vapour can be provided by any suitable method apparent to a person skilled in the art. For example only, although not shown in the drawings, a heating element and a volume of liquid may be provided in the humidity adjusting device 1 1 humidity adjusting device 1 1 wherein on activation of the heating element liquid begins to evaporate; or a volume of liquid alone can provide moisture vapour through unaided evaporation. Alternatively, damp or wet salt can be provided as a source of moisture vapour. It will be appreciated that the humidity adjusting device 1 1 may also be operable to remove moisture from the test chamber in order to establish the required %RH in the test chamber. In this variation, salt can act as a moisture absorbing substance.

Both the inlet port 15 of the first container 9 and the outlet port 25 of the humidity adjusting device 1 1 are located within the sealed enclosure structure 17.

A separate %RH sensor (not shown) may be provided in the first container

9to monitor the level of %RH in the first container 9 in addition to the %RH sensor 27.

The device 7 includes a control unit 29 for controlling the opening/closure of the inlet port 15 of the first container 9 and the outlet port 25 of the humidity adjusting device 1 1 . Although not shown in the drawings, the control unit 29 may include an electrical or an electromechanical actuator and an electronic control module for controlling the opening/closure of the ports 15, 25. The electronic control module preferably includes a programmable electronic processor. A number of ways to provide a control means would be apparent to a person skilled in the art.

In order to test the ERH of a sample, the sample is placed into the test chamber of the first container 9 through the open end 19 of the first container 9 and the closure member 21 is placed over the open end 19 to sealingly close the open end 19 of the first container 9. The control unit 29 then controls opening/closure of the inlet port 15 of the first container 9 and the outlet port 25 of the humidity adjusting device 1 1 as follows: after the sample has been placed into the test chamber, the inlet port 15 of the first container 9 initially remains closed while the outlet port 25 of the humidity adjusting device 1 1 is opened to establish a predetermined %RH therein (Figure 2); once the predetermined %RH is reached in the enclosure structure 17, the outlet port 25 of the humidity adjusting device 1 1 is closed and the inlet port 15 of the first container 9 is opened so that moisture vapour from the enclosure structure 17 is allowed to migrate between the test chamber and the interior of the enclosure structure 17 (Figure 3); once humidity equilibrium has been reached in the enclosure structure 17 and in the test chamber, the inlet port 15 is closed and the ERH of the sample is recorded.

In the presently described embodiment, the inlet port 15 of the first container

9 is provided by two telescopic tubular upper and lower portions 31 , 33 arranged to move relative to each other between a closed position and an open position. In a first, open, position (Figure 3) the portions 31 , 33 are moved apart and a gap 35 is defined between the two portions 31 , 33 and moisture vapour is allowed to access or leave the test chamber. In a second, closed, position (Figure 2) the lower portion 33 is moved upwards so that upper portion 31 is received in the lower portion 33 and the gap is closed and the moisture vapour is prevented from accessing or leaving the test chamber.

In the presently described embodiment, the humidity adjusting device 1 1 is provided in the form of a second container 37, similar to the first container 9. The second container 37 defines a moisture chamber (not indicated by a numeral) for accommodating a source of moisture or a moisture absorbing means and an open end 39 (shown closed in the drawings) for receiving a source of moisture or a moisture absorbing means therethrough. The second container 37 includes a closure member 41 placeable over the open end 39 of the second container 37 for closing and sealing the open end. The open end 39 of the second container 37 is located on 17 external side 23 of the enclosure structure 17 to allow moist matter to be placed into the second container 37 from outside the enclosure structure 17. The second container 37 is sealingly connected with the enclosure structure 17 around the open end 39 of the second container 37. In this way, access into the second container 37 from outside the enclosure structure 17 is only allowed though the open end 39 of the second container 37.

In the presently described embodiment, the outlet port 25 of the second container 37 is provided by two telescopic tubular upper and lower portions 43, 45 arranged to move relative to each other between a closed position and an open position. In a first, open, position (Figure 2) the portions 43, 45 are moved apart and a gap 47 is defined between the two portions 43, 45 and moisture vapour is allowed to egress or access the second container 37. In a second, closed, position (Figure 3) the lower portion 45 is moved upwards so that the upper portion 43 is received in the lower portion 45 and the gap is closed and the moisture vapour is prevented from egressing or accessing the second container 37.

Other ways of implementing the humidity adjusting device 1 1 and the outlet port in the enclosure 17 are possible as will be appreciated by a person skilled in the art.

The device 7 of the present invention is particularly suitable for testing and characterising pharmaceutical materials. The pharmaceutical material may be in any suitable form. For example, the pharmaceutical material may be a one piece object, such as, for example, a tablet or a capsule. The pharmaceutical material may also be in the form of a flowable substance, such as a powder or viscous liquid, for example, a gel, cream or lotion. The material to be tested may be a drug active substance, other powder or a mixture/formulation thereof, cosmetic, agrochemical, herbal, excipient or other pharmaceutical material.

It will be appreciated that the first container 9, the second container 37 and the enclosure structure 17 may be of any suitable shape as long as the shapes allow the enclosure structure 17 to accommodate therein the first container 9 and the second container 37.

The first container 9 and the second container 37 may be made of any suitable material including metal, glass or plastic, such as High Density Polyethylene (HDPE) or laminated materials, wherein same or different materials may be laminated. For example only, a plastic container may be coated with a layer of metal or other suitable moisture barrier to enhance its moisture impermeability.

Modifications are possible within the scope of the invention as will be apparent to a person skilled in the art, the invention being defined in the appended claims.