Most of the drugs people take every day are in tablet form. As ubiquitous as tablets are, their manufacture, from tablet press to coating, is challenging. They’re vulnerable not only to the effects of moisture, but also to changes in tablet press settings, or dryer or coating temperature changes.
Between 2008 and 2011, according to Fette Compounding Inc., FDA issued 42 Warning Letters to pharmaceutical manufacturers involving the recall of tablets. These problems, Fette says, could have been caused by a failure to use improved features on presses themselves, such as security features that prevent setting changes, but might also be traced to operator errors, which may have been caused by incomplete training.
A number of companies are using process analytical technology (PAT) to help control the drying and coating processes and reduce variability in tablet operations.
As Benoit Igne, of Duquesne University (Pittsburgh), discussed in a September webcast on spectroscopy for PharmaManufacturing.com, closer control of the tableting process demands a better understanding of critical process parameters and critical quality attributes.
Igne summarized research undertaken with Daichi Sankyo Co. At the university, the researchers determined that the critical process parameters included pan rotation speed (the wrong speed could lead to erosion, breakage or winning), batch size, inlet and exhaust air temperature, inlet air volume, spray rate and time.
Researchers monitored the coating and drying endpoint temperature, and applied Near Infrared Spectroscopy (NIR) in situ within the pan coater to estimate weight gain, moisture and tablet coater temperature.
Other PAT methods are also being used to improve tableting. Teraherz imaging, for instance, is being used to study coating thickness, to optimize that parameter, and with it, dissolution time.
Three-dimensional imaging, using Innopharma Labs’ eyecon analyzer, allows for better particle characterization to improve tableting, while hyperspectral imaging, combining the strengths of spectroscopy and imaging, is also being applied to improve tableting.
In the meantime, process equipment is being improved to ensure reproducibly high standards of tablet quality. Here is a sampling of recent tableting equipment introductions that seek to maintain final product quality.
Monitor Four Critical Tableting Parameters at Once
Fette Compacting’s Checkmaster has been designed to allow users to measure, automatically, the four key tablet parameters that affect product quality: Weight, thickness, hardness and diameter. A washable version of the equipment is also available.
The Checkmaster can be integrated completely into the in-process control system. With this, measurements are continuously assessed and recorded. In this manner, the self-regulation of the tablet press is also possible. FETTE • www.fetteamerica.com
More Affordable Tablet Analysis
Natoli Engineering Company has introduced an affordable range of tablet analysis equipment, including tap density, dissolution, friability, powder flow and tablet hardness testers. Measuring 10 by 3 inches, the company’s new, portable, handheld hardness tester can be used in the laboratory or manufacturing areas. Although this device is powered by batteries, there is an option for printer attachment, when validation is required. The tester is capable of measuring 2mm to 28mm tablets with a hardness range up to 500 Newtons. NATOLI • www.natoli.com
Press Designed for Large Tablets
In the past, the production of large tablets could lead to even larger problems such as low production rates on the one hand and worn out presses and tooling on the other. But this 51-station, double-sided Hata press allows for both high compression and high output, even with one-inch-diameter tablets. When used with D-sized triple-cavity tooling, the press can produce up to 21,420 tablets per minute at 70 rpm, depending upon tablet size and granulation characteristics. ELIZABETH-HATA INTERNATIONAL • www.eliz.com/Hata/hata.php
Press Features Integrated Control, Helps Prevent Cross-Contamination
The Express 700 double-sided press offers automatic weight control of each layer and complete segregation of different materials, preventing cross contamination and applying a well-defined demarcation line. A single layer tablet press can be converted to the bi-layer version at any time in the future by means of a retrofit conversion kit.
The company’s mpower integrated control technology provides for the control and adjustment of all the main press parameters and acts as the means of communication to ancillary equipment, and facilitates detailed batch reporting on compression data, online sampling analysis, rejected tablet details, all machine adjustments, product information and alarms. MANESTY • www.manesty.com
Resources: Improving Tableting Operations & Product Quality