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February 1997

Tablet sampling - a new process for quality control and general tablet development

Cambridge Consultants Ltd (CCL®) has patented and developed a novel automated process for tablet dissolution known as the Tablet Processing System (TPS).

The idea arose from a site visit to a major Swedish pharmaceutical company together with marketing discussions with UK-based companies which confirmed that the opportunity was genuine. In fact, the requirement was so evident that CCL invested funds and has built a prototype demonstrator which is being used in laboratory trials.

The objective of the machine is to accept a tablet, release its contents and dissolve it for subsequent auto-sampling or similar test. Automated homogenisers and grinders which perform this function have been in existence for some time but these processes have been shown to destroy some of the more delicate compounds in the tablets. Inevitably these machines also generate waste solvents and the potential for contamination between samples.

This process has two main applications: where a guarantee of absolute precision is required, such as in the development of tablets, or where automated on-line sampling is essential, such as in Quality Control of tablet production

Method of Operation

The machine uses two webs of laminate-reinforced polypropylene (other materials are possible) to form a sachet. The tablet is dropped into the sachet, during which time it comes into contact only with its own sachet material. The tablet is then crushed through the sides of the sachet, using vibration and compression up to 10,000 Newtons. Even so, this action is very gentle - only just enough force is used. As the pill cracks, the crusher control loop senses the decrease in force and the crushing jaws may be retracted according to a menu-selectable crushing strategy.

Next, the solvent and any reagents may be added from a syringe pump directly onto the crushed tablet. The sachet is then sealed and dispensed, but not before it has been date-stamped and barcoded by an in-built thermal transfer printer.

As one sachet is being dispensed, the next is being created. The machine may then power down to a dormant state if it is not required. But the sachet is always ready for the next tablet and the instant that one is detected, the TPS switches on and starts to process it.

By this method, we have a carefully controlled process which retains 100% of the tablet contents and can use a minimum quantity of solvent. There is absolutely no chance of carry-over, since a new sachet is created every time. To comply with FDA stipulations, the inside of the sachet touches no part of the web-feeding process. The sachet webs are passed around the outside of the equipment so that there is no part of the machinery above the sachet material. Finally, the polypropylene sachet material has been chosen for its inertness and sealing qualities and it is specified in an approved pure form.

Any number of solvents may be introduced at the addition stage. Equally, reagents can be added in precise quantities to assist with subsequent analysis. For example, colorimetric reagents may be added at this time for subsequent spectrophotometric evaluation. The sachet walls are transparent and on-line photometry is possible.

What has been achieved so far

A prototype machine has been under trial by the Swedish company. To date, all of the features and benefits have been demonstrated. This includes working with genuine test samples and solvents. So far, the tests have enabled the Swedish company to detect the lowest concentrations of active ingredient in the dissolved tablets, using combinations of tablets and solvents which have previously not yielded satisfactory results.

The potential is there to examine the sachets for signs of undissolved samples. After the sachet has been dispensed, it can be shaken, 'sonicated', manipulated or even warmed to assist dissolving. The machine equipment has the facility to sonicate the sachet before it is dispensed, using the in-built variable-frequency vibrator.

Throughput and Cost

Currently, the machine generates 2 samples per minute at a cost of 10p per sachet. The speed can be greatly increased if required. More than half of the time taken, for instance, can be attributed to the solvent addition stage; for more easily dissolved pills, quicker crushing cycles can be specified.

What remains to be completed

The machine is currently being modified according to a specification which has been agreed with the Swedish company. The specification details how the prototype will be converted into the fully developed machine. For the core machine, this includes the design of the screen menus and modifications to the way the data will be presented.

The Swedish company requires the 'front end' of the machine to be enhanced with a bowl feeder and weighing station so that the machine can automatically feed batches of multiple tablets.

The output from the machine has not been decided. Manually feeding a HPLC using a hypodermic is sufficient for a development laboratory; the company is also keen to match the development investment with a Quality Control system for its production equipment. In this case, CCL may be asked to add a post-processor sampling and resealing module.

Future plans

The process has been patented and development has been entirely funded by Cambridge Consultants Limited. The prototype machine is available for evaluation by all interested parties and CCL now seek further trial work from interested pharmaceutical companies.

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