June 20, 2013

The tablet remains the most popular dosage form and tabletting equipment has evolved significantly over the last decade to accommodate the ongoing demand for its advancement. Big pharma and their generic opponents increasingly seek to gain the competitive edge, producing tablets that boast improved ‘drug delivery’ capabilities, attained through the application of taste-masking, enhanced solubility and timed/delayed release technologies.

EPM Editor Elizabeth Valero consulted key representatives at tabletting equipment providers on current trends and key factors for achieving the fast and economical production of high-quality tablets.

Participants:

Ryan Keefer, General Manager at Elizabeth-Hata International, a division of Elizabeth Companies.

Steve Deakin, Business Development Director at I Holland Ltd.

Stefania Barzanti, Marketing Manager at IMA S.p.A.-IMA Active.

Charles Kettler, Director at Natoli Scientific, a division of Natoli Engineering Company, Inc.


‘Sticking’ and ‘picking’ (where product adheres to the punch faces or within the embossing of the tooling), are cited as the most common and costly issues during tablet production, resulting in substantial losses of product and lengthy periods of downtime, how can their occurrence be minimised or eliminated?

Keefer: Elizabeth’s tablet design staff work with customers to maximise the overall tablet design and eliminate areas in the tablet configuration that could cause sticking and picking. Certain tablet design characteristics can be utilised on the punch face to reduce and eliminate these issues.  

Another alternative method is the use of specific tool steel coatings that can be used to reduce sticking and picking on the punches. Depending on the product application and type of tool steel being used to manufacture the punches, there are several good coatings that can be used to help resolve these issues.

Deakin: Good tablet design can often reduce the possibility of both sticking and picking. Whilst picking can normally be eliminated completely by design changes, the root cause of sticking can be attributed to many different factors associated directly with the type of formulation; Van der Waal Forces and capillary action for example. The use of anti-stick tool coatings is now accepted across the industry as these new and innovative coatings or treatments can eliminate sticking.

It has always been difficult to persuade people to try different coatings owing to the additional costs involved, but now there are good case studies available showing the increased production value of such coatings.

Specialised coatings can significantly increase the price of tooling but when successful, the savings clearly outweigh the additional costs as the increase in product yield and manufacturing efficiency is easily quantifiable.

When selecting the correct coating, it is essential to share the full details of the problems being experienced so the correct recommendation can be made.

Barzanti: Reasons for sticking and picking can be related to the product to be compressed, like quality and characteristics of the raw materials — for example, particle size and moisture content — plus inconsistent wetting and drying during granulation, lack of lubricant or inefficient blending.

A careful drying process is essential to achieve a more consistent blend. Lubricants must be properly screened to remove over-sized particles and must be evenly blended into the formulation. When sticking is related to a melting and/or hygroscopic powder, achieving compression at a low temperature and low humidity can help a lot in solving the problem.

Also, the tablet press can be adjusted to minimise these problems, reducing punch penetration and increasing dwell time; while with a gravity press to extend dwell time it is necessary to reduce the speed, with our Comprima tablet press dwell time can be easily extended by playing with the compaction and pre-compression axis.

In some cases, changing the tool surface finish is enough to stop sticking and picking; chrome plating, for instance, produces a smooth and non-adherent face on punches and this can be a solution.

Kettler: Many of the sticking and picking problems that we see are due to required changes in process variables as the product moves from clinical supply production to larger scale product launch manufacturing, often after the formulation has been submitted and accepted by the regulatory agency.

The desire to have a direct compression formulation, driven by the perceived capital and labour cost reduction, often prompts a speed to market mentality that limits the R&D required to design a formulation that runs with minimal problems at both production scales.

Adhering to a well-thought out drug product design process and flowchart can minimise future problems by identifying the potential risks and addressing them through thoughtful studies. Having qualified and experienced drug formulators who can utilise their experience of past successes and failures is key to knowing what studies are required and what the consequences are when data are not generated to address the risks identified during the drug product failure mode and effects analysis (FMEA).


To what extent is quality and consistency of tablets contributable to choice of excipient and granulation specs and flow?

June 20, 2013

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