GB2308184A

GB2308184A - Detecting particles in suspension

Info

Publication number: GB2308184A
Application number: GB9525426A
Authority: GB
Inventors: Philip Anthony Jinks; Robert Bent
Original assignee: Individual
Current assignee: Individual
Priority date: 1995-12-13
Filing date: 1995-12-13
Publication date: 1997-06-18
Also published as: GB9525426D0

Description

A NOVEL APPARATUS FOR DETECTING PARTICLES IN SUSPENSION Field of the invention This invention concerns apparatus for detecting particles and changes in particle size in a suspension and inter alia is concerned with an optical detection system enabling samples in transparent vials, in particular of metered dose inhaler suspension formulations, to be analysed.

Background to the invention Apparatus for detecting changes in particle size in suspension is described in British Patent Specifications 21 29549A and 21 82432B. The specifications concern apparatus and improvements to apparatus for detecting particles in suspension.

The apparatus consists of a clamping arrangement for a flexible tube through which suspension is forced to flow. The clamping arrangement allows a narrow light pathway to be formed across the sample tubing and a photodetector provides output in the form of a continuous analogue signal.

The suspension formulations of pressurised metered dose inhalers present a challenge to characterisation in terms of the measurement of aggregation rates and creaming or sedimentation rates. It is important however, to understand such suspension behaviour since the dosing uniformity of these products and their stability characteristics are largely influenced by these dynamics. The high pressure of the formulations renders techniques such as the flow through apparatus described in the previous paragraph unsuitable for such measurements. In addition, such apparatus only provides information on the degree of aggregation of the suspension at set flow rates in the environment of a narrow tube and not the degree of aggregation that would occur in the metered dose inhaler product itself.The latter is the important measure, since flow through a tube can easily break up the weakly bound aggregates which are a typical feature of metered dose inhaler suspension formulations.

In addition to the degree of particle aggregation of a metered dose inhaler suspension, the rate of aggregation after agitation of the inhaler formulation and the creaming or sedimentation rate after agitation, are of key importance to both the dosing performance and the stability of the product. There are however, currently, no effective means of quantification of these parameters.

This invention addresses the latter issue and relates to apparatus for the measurement of the degree and rate of aggregation and of creaming or sedimentation of suspensions. The technique is of particular application to metered dose inhaler suspension formulations where the suspension characteristics can be measured in the environment of a closed transparent vial of circular cross section, of similar dimensions to those of typical metered dose inhaler products.

Description of the invention The invention relates to an apparatus consisting of one or more height adjustable aligned photoemitters and photodetectors whereby light is emitted and received in a narrow beam across a pathway into which a transparent vial is inserted. The photoemitters and photodetectors may preferably be situated remotely from the sensing zone and connected to the sensing zone by fibre-optic cable, terminating in aligned probes of narrow dimension.

A specific embodiment of the invention will now be described by way of example.

With reference to Figure 1, two infra-red emitter/detector units utilising light of 880 nm are linked by fibre optic cable 1, to two pairs of aligned emitter/detector probes 2, of tip diameter 1 mum. Each pair of aligned emiter/detector probes is held in a rigid, height adjustable mounting 3. An important feature of the emitter/detector probes is that they feature a small cross sectional area, resulting in the emission and detection of light in a narrow beam, such that interruption of the light by particle aggregates, creates fluctuations in the measured light intensity. The signal fluctuation characteristics relate to the size of aggregates in the suspension.In addition to signal fluctuations, the gross change in signal with time indicates the creaming or sedimentation rate of the suspension, since the light detected by the detector unit will increase almost exponentially as the suspension becomes more dilute. A further feature of the probes is that they are positioned to form a minimum clearance between their sensing tips and the walls of an inserted transparent test vial. This is in order to minimise the collection of stray light The use of two emitter/sensor probe units; one close to the base and one close to the surface of the suspension in the test vial, allows simultaneous measurement of events occurring at these two critical regions and thus makes the apparatus sensitive in the monitoring of creaming and sedimentation behaviour.

The accurate positioning of the emitter/detector probes is important to allow reproducibility in the test conditions. The positioning of each height adjustable mounting is controllable using the knurled knobs 4, which raise and lower the positions of the probe mountings relative to the sample holder 5, and simultaneously activate digital encoders mounted beneath the sample holder baseplate 6. Each digital encoder is linked to a digital display which registers the vertical movement changes in millimetres of the probe mounting relative to the sample in the sample holder. The sample holder is designed to accommodate a transparent test vial (15ml) of circular cross section. Such vials when fabricated from polyethylene terephthalate (PET) are capable of containing safely, the pressure generated by metered dose inhaler formulations and are able to transmit light from the apparatus. The two matched pairs of emitter/detector units are used to provide simultaneous signals from accurately selectable points on the suspension column. The voltage signals from the photodetectors are processed through analogue to digital converters and the digital information is then sampled over experimental run times of selectable duration using custom written software, to create files of 1000 data points. The files are then processed using readily available software for the creation of charts.

The apparatus has the additional feature of adjustable incident light intensity and this enables effective measurement on suspensions over a wide concentration range.

Claims

1. A particle analyser which comprises a housing for the vertical placement of a transparent test vial containing a suspension, a light source and one or more height adjustable photosensors which feature a detection region of small surface area.

2. A particle analyser according to claim 1 in which the height of a photosensor is adjustable using a digital encoder linked to a mechanical height adjustment mechanism.

3. A particle analyser which comprises a vial housing for the vertical placement of a transparent test vial containing a suspension and one or more height adjustable aligned matched pairs of light emitterisensor probes which create a narrow optical light pathway across a sensing region.

4. A particle analyser according to claim 1 or to claim 3 in which the vial housing is designed for the insertion of a transparent vial of circular cross section and, after insertion of said vial there is a minimum gap formed between the walls of the vial and the emitting and receiving probes.

5. A particle analyser according to claim 1 in which the light source and the means of detection are situated remotely from the suspension vial housing.

6. A particle analyser according to claim 1 or to claim 3, in which one or more light sources can be varied in intensity.

7. A particle analyser according to claim 1 or to claim 3, in which the signal from one or more photosensors is converted from an analogue to a digital signal.

8. A particle analyser according to claim 7, in which the digital signal is sampled over variable run durations and stored in a data file.

9. A kit of parts comprising an analyser according to any one of claims 1 to 8.

10. A method of analysing particles in suspension in which a suspension sample in a transparent vial is placed vertically in a housing and one or more height adjustable photosensors which feature a detection region of small surface area, are used to detect changes in suspension particle size.

11. A particle analyser substantially as herein described with reference to the accompanying drawing.