METHOD AND APPARATUS FOR MECHANICAL PROCESSING OF A SAMPLE AND A MEMBER OF SUCH AN APPARATUS

Abstract: A method for mechanical processing of a plastic or elastic pharmaceutical or confectionery sample for the release of substances from said sample into a surrounding liquid medium, comprises immersing a reinforcing member into said medium, immersing said sample into said medium and subjected said sample and said member essentially simultaneously to repeated compression and shearing forces. An apparatus for carrying out said method comprises a substantially vertical container (1) releasably mounted on a base (2) and a first jaw (7) for receiving said sample (17) fixed on said base (2) and arranged in the lower end of said container (1). The lower end of said container (1) is sealed against leakage of said liquid medium. A second jaw (15) faces said first jaw (7) and is vertically movable and rotatable for subjecting said sample (17) to compression and shearing forces. The apparatus further comprises drive means (14, 16) for said second jaw (15) and a separate member (18) for reinforcing the sample (17).

Description: METHOD AND APPARATUS FOR MECHANICAL PROCESSING OF A SAMPLE AND A MEMBER OF SUCH AN APPARATUS. The present invention relates to a method and an apparatus for mechanical processing of a plastic or elastic sample and to a member of such an apparatus. For studying the properties of a plastic or elastic sample when subjected to mechanical processing, an apparatus is needed which makes it possible to carry out reproducible tests. Present-day techniques comprise e.g. a masticating device as disclosed by Kleber et al. in Journal of Dental Research, 60 (1981) :2, pp 109-114, which is used for in vitro assessment of the abrasive effects of chewing gum on teeth, and a measuring device as described by Christrup et al. in Arch. Pharm. Chem. Sci., 1986, 14, pp 30-36, which is used for in vitro measurements of the release of substances included in a chewing gum. The prior art devices comprise two mutually reci- procatory jaws or pistons which are disposed in a con¬ tainer and between which the sample is to be processed. The properties which may be of interest to deter- mine thus are, inter alia, the action exerted by the sample on the pistons or some part thereof, the plas¬ ticity of the sample and/or the release of substances included in the sample to a liquid surrounding it, all as a function of the processing time and/or the processing technique. The purpose of the determina¬ tion may be comparative, i.e. primarily for quality control, and/or imitative, e.g. with respect to in vivo processing by chewing. A particularly interesting field for using such mechanical processing apparatus is the processing of pharmaceutical preparations in the form of plastic samples, preferably chewing gums, in which case it should be possible in a reproducible manner to deter- mine the period of time during which active substances in the sample are released to a liquid surrounding the sample. In addition to the processing technique, the re- lease of substances may be affected by the components included in the chewing gum, such as consistency agents, softeners, preservatives, gum bases, flavourings, as well as active substances in the form of drugs or nico¬ tine, but also by the method of making the chewing gum. Further, the release is affected by the environment in which it takes place, i.e. the temperature and the com¬ position of the liquid surrounding the sample, and the apparatus should be able to maintain at least the tem¬ perature constant. One drawback of the prior art devices is the problem of cleaning the container or reservoir in which the sample is processed. The tendency of the sample to move or spread outside the processing area of the pistons or jaws has also been observed in the prior art devices. Another problem concerns the fact that the sample tends to adhere sometimes to one jaw, sometimes to the other and, above all, to separate parts floating freely in the liquid and escaping further processing. ι n view of these problems, it is therefore very difficult to obtain an exact and reproducible processing of the samples by using the prior art devices. From this of course follows that it will not be possible to obtain reliable and reproducible release rates which can be used for scientific or manufacturing purposes. The most important object of the present invention thus is to provide an apparatus and a method for mechani¬ cal processing of a pharmaceutical or confectionery sample in a reproducible manner. To sum up, the present invention concerns an apparatus for mechanical processing of a pharmaceutical or confectionery plastic or elastic sample for the release of substances from the sample into a surrounding liquid medium. The apparatus includes a substantially vertical container releasably mounted on a base. The apparatus also comprises a first jaw for receiving the sample. This jaw is fixed to the base and arranged in the lower end of the container. Means for sealing the lower end of the container against leakage of the liquid are also provided. A second jaw facing the first jaw is vertically movable and rotatable for subjecting the sample to compression and shearing forces. The apparatus also includes means for driving the second jaw. Preferably, the apparatus also includes means for controlling the temperature of the liquid medium. According to the invention, it has also been found that in cases where a high degree of accuracy and reproducibility is required, a separate reinforcing member which may be in the form of a flat and/or disc¬ shaped device or member should be processed at the same time as the sample. By using this disc-shaped device or reinforcing member the sample will hold together and can be prevented from splitting up into several pieces or from otherwise moving outside the processing area between the jaws. To permit a substantially free movement within the material of the sample during processing, the disc-shaped member suitably is foraminated. This also increases the adherence between the member and the sample, making it more vigorous than the adherence be- tween the sample and the jaws. The disc-shaped member may advantageously be a net or a perforated disc and consist of plastic, e.g. nylon or any other material which is inert to the components in the sample and to the liquid in which the sample is processed. It is furthermore preferred that the container is double-walled and made of a transparent material, such as glass or plastic. The flexibility of the appa¬ ratus is further increased if the distance between the jaws can be adjusted and, to this end, the upper jaw is preferably mounted in such a way that it is vertically adjustable. The surfaces of the jaws facing each other suitably are friction surfaces, i.e. exhibit a relatively large friction with respect to the sample. A particularly suitable feature is however using smooth friction sur¬ faces, in which case the necessary friction may optional¬ ly be achieved by blasting. Completely smooth surfaces may however also be used. In such case, the jaws will be very easy to clean, which is of importance to prevent a sample from contaminating the following sample and so forth. In order to ensure stirring of the liquid in the container during processing, at least one jaw suitably forms a gap with the inner wall of the container. The movement of the upper jaw may be purely reci- procating, but in order to imitate in vivo processing of a chewing gum, the apparatus may preferably have means for rotating the jaws relative to each other when in their turning positions closest to each other. The invention also comprises a method for mechanical processing of a plastic or elastic pharmaceutical or confectionery sample for the release of substances from the sample into a surrounding liquid medium, comprising immersing a reinforcing member in the medium, immersing the sample in the medium, and subjecting the sample and the member essentially simultaneously to repeated compression and shearing forces. Preferred embodiments of the invention will now be described in more detail hereinbelow with reference to the accompanying drawing in which Fig. 1 is a longi- tudinal section of an apparatus according to the inven¬ tion, and Fig. 2 is a top plan view of a device accord¬ ing to the invention. Fig 3 is a diagram showing release of nicotine versus time. The embodiment shown in Fig. 1 of an apparatus according to the invention comprises a cylindrical, double-walled container 1. A base 2 consists of a base plate 3, a spacer plate 4 and a sealing plate 5 which are held together by a stud bolt 6 on which a fixed jaw 7 can also be screwed. A spacer sleeve 8 encloses the jaw 7 and is removably mounted and non- rotatably connected to the jaw 7 by means of a stop screw 9. The lower open end of the container 1 can be passed over the sleeve 8 with liquid-tight fit with respect thereto. A collar 10 with a flange 11 is glued to the lower end of the container 1. An O-ring 12 is mounted in mating grooves in the flange 11 and the sealing plate 5 which are pressed against each other by means of a clamping member 13. A second jaw 15 is removably mounted on a reciproca- tory piston 14, such that the jaw 15 is located above the jaw 7. The jaw 15 can be reciprocated relative to the jaw 7 by drive means (indicated at 16) and has adjust¬ able stroke length, stroke velocity and stroke frequency. The drive means 16 can also be arranged to rotate the jaw 15 relative to the jaw 7, especially when the jaw 15 is in its turning position closest to the jaw 7. In Fig. 1, there is also shown a sample 17 which partly encloses a disc-shaped member 18 according to the invention. The disc-shaped member 18 more spe¬ cifically is in the form of a net, as shown in more detail in Fig. 2, and is circular, having a slightly smaller diameter than the inner diameter of the con¬ tainer 1, for instance 1 mm less. The net 18 has a higher adhesive capacity with respect to the sample 17 than the jaws 7, 15. Instead of a net, the disc-shaped member 18 may consist of any other foraminated member, for instance a perforated disc. The member 18 should be substantially two-dimensional, i.e. have but a small extent in the direction of movement of the jaw 15. Alternatively, the member 18 could however also be a spacer element determining the minimum distance between the jaws 7 and 15, i.e. the lower end position of the jaw 15. - Since the container 1 is double-walled, it can be used for thermostatting a liquid contained therein, such as water or artificial saliva. The container may consist of glass, plastic or other suitable mate¬ rial that does not react with the liquid used or any of the components in the sample 17. The surfaces 19, 20 of the jaws 7, 15 facing each other are friction surfaces which may be formed with grooves, notches or other irregularities to re¬ tain the sample 17 when it is subjected to pressure and rotation by the jaws 7, 15. However, the required friction can also be achieved by means of smooth sur¬ faces, which of course makes it easier to clean the jaws 7, 15 between different processing operations. It is desirable to have a gap between the piston 15 and the inner wall of the container 1. The size of this gap is suitably determined empirically on the basis of e.g. the desired stroke frequency, the volume of the sample and the liquid volume to be dis¬ placed. Since it is often desirable to have liquid solutions with as high a concentration as possible of substances released from the sample during the processing, the liquid volume in the container should be relatively small and thus also said gap. For analysing substances released from the sample 17, the apparatus may comprise different types of probes for measuring pH and temperature, and for auto¬ matic measurements of the composition of the liquid etc. To determine e.g. the release of different sub¬ stances in a sample 17, the apparatus described above can be used in the following way. The sample 17 and the member 18 are placed on the jaw 7, whereupon a suitable liquid is supplied to and thermostatted in the container 1. The jaw 15 is thereafter set in mo¬ tion according to a predetermined movement pattern, and sampling from the liquid container 1 is perform¬ ed at preselected points of time, whereupon the sample or liquid phase is analysed with respect to the sub¬ stance or substances the release of which should be measured. During processing, the plastic sample 17 will be flattened and partly enclose the member 18 thus perform- ing a reinforcing function and holding the sample 17 to¬ gether. If, nevertheless, parts of the sample 17 should be torn loose from the side thereof located below the member 18, this will prevent the separated parts from moving upwards into the liquid. In this way, the sepa- rated parts can again be easily integrated with the sample reinforced by the member 18. Since the spacer sleeve 8 extends higher than the jaw 7, the member 18 tends to lift the sample 17 off the jaw 7 between each stroke of the jaw 15. The invention is further illustrated by the follo¬ wing Examples Example 1 Samples of Nicorette chewing gum were weighed. The casing of a double-walled container in an apparatus according to the invention was filled with water to be circulated and having a temperature of 37°C. An aqueous solution containing 0,1% artificial saliva was heated to 37°C and poured in the container. A sample of Nicorette was immersed into the aqueous medium in the container and placed on the jaw. The upper jaw was actuated to move to a depressed position for fixing the sample. After about 5 min, temperature equilibrium between medium and sample had been reached, and the upper jaw was actuated to move up and down, executing a rotary movement when in its lowest turning position in order to repeatedly subject the sample to compression and shearing forces. Example 2 Example 1 was repeated, however with a disc-shaped net immersed into the medium in the container together with the Nicorette sample. Volumes of 0.5 ml of the medium were withdrawn from the container after respecti¬ vely 2, 5, 10, 20, 30 and 45 min, and the amount of nicotine in each volume was analysed by standard methods. The results (mean values of 6 samples) are given in the diagram of fig 3. It is evident to a person skilled in the art that several different modifications of the embodiments described above are possible within the scope of the invention, such as it is defined in the accompanying claims.

Claims: CLAIMS 1. Apparatus for mechanical processing of a pharma¬ ceutical or confectionery plastic or elastic sample (17) for the release of substances into a surrounding liquid medium, comprising a substantially vertical con- tainer (1) releasably mounted on a base (2); a first jaw (7) for receiving said sample (17) which is fixed on said base (2) and arranged in the lower end of said container (1) ; means (8, 10-12) for sealing said lower end of said container (1) against leakage of said liquid medium; a second jaw (15) facing said first jaw (7), said second jaw (15) being vertically movable and rotatable for subjecting said sample (17) to compression and shearing forces; and drive means (14, 16) for said second jaw (15). 2. Apparatus according to claim 1, wherein the container (1) is a cylinder. 3. Apparatus according to claim 2, wherein the cylinder (1) is double-walled and made of a transparent material, preferably glass. 4. Apparatus according to any one of the preceding claims, further comprising a separate member (18) for reinforcing the sample (17). 5. Member for reinforcing a pharmaceutical or con- fectionery, plastic or elastic sample to be mechanically processed, c h a r a c t e r i s e d in that it is essentially disc-shaped and foraminated. 6 . Member according to claim 5 , c h a r a c t e ¬ r i s e d in that it is a net . 7. Method for mechanical processing of a plastic or elastic pharmaceutical or confectionery sample for the release of substances from said sample into a surroun¬ ding liquid medium, comprising immersing a reinforcing member in said medium, immersing said sample in said medium and subjecting said sample and said member essen¬ tially simultaneously to repeated compression and shearing forces.

Inventors: LILJEWALL LARS RAGNAR, LILJEWALL, LARS, RAGNAR
Applicants: LEO AB, AKTIEBOLAGET LEO
Application year: 1988
Main classification: G01N1
IPC codes: G01N1, G01N33