Production and QC Challenges with mini-tabs
The continued growth in demand for mini tablets (micro-tablets or mini-tabs) is hardly surprising given the benefits that they can deliver for healthcare professionals and their patients. Their small size makes them more suitable for paediatrics and those with dysphagia (difficulty swallowing). But perhaps more interesting is the flexibility that they offer for combining multiple drugs, in easily varied quantities, either within a single capsule or combined with suitable excipients to create modified release profiles, similar to multiple unit pellet systems (MUPS).
However, whilst mini-tabs are manufactured using proven processes and much of the same equipment as larger tablets, they do present some substantial production and quality control challenges.
A common thread running through the development, formulation, trialling and quality control of pharmaceutical products is the need to check and ensure uniformity of weight. With mini-tabs, both manual and automated weighing operations become significantly more difficult and, in some cases, require new approaches:
Tighter tolerances demand greater precision
As with other solid forms, weight uniformity of mini-tabs is crucial for accurate dosing. However, the tolerance for weight variability in mini-tabs is less than for larger tablets, because small absolute weight variations equate to larger relative variations in potency.
Individual weight
Precision required for ±5% control
7mg mini-tab
± 0.35mg
20mg mini-tab
± 1.00mg
300mg tablet
± 15.00mg
Fig 1. Examples of absolute vs relative weight variability
As demonstrated in Fig.1 above, the precision required in manufacturing mini-tabs can be an order of magnitude greater than for regular sized tablets. This means that far greater consistency is required from process equipment. It also means that existing process controls are unlikely to provide sufficient advance warning of issues such as variability and drift. Sampling which relies on monitoring the average of multiple tablets is unlikely to provide the insight needed to foresee and correct against batch failure.
Manufacturers of mini-tabs will almost certainly require more frequent in-process sampling, using automated check weighing of individual mini-tabs, to a high degree of precision.
Relative weight of coatings presents checking challenges
Coatings can be applied to mini-tabs using the same techniques as with larger tablets. However, due to the much higher surface to volume ratio of mini-tabs, it takes proportionally much more weight of coating to achieve the required thickness.
Consequently, with the coating comprising as much as 10-15% of the final product weight, variance in the coating could cause an otherwise acceptable batch to be nudged beyond the acceptable weight limit. There is also a real concern that an out of tolerance batch could be accepted if variance in the coating balanced out the under or over weight in the active product.
Given these issues, it may be necessary to carry out check-weighing of mini-tabs before they are coated.
Very small sizes rule out many handling approaches
The exceptionally small size of mini-tabs can present substantial handling issues. In small scale laboratory settings, where manual weighing may have been the preferred approach, picking up mini tabs with tweezers can be exceptionally challenging and become a lot more time-consuming and prone to accidents.
With larger production volumes, inline tablet weighing machines are simply not designed to handle and weigh mini-tabs. With no direct substitute, the best alternative will probably involve in-process sampling (as described above), with high precision weighing machines that balance speed with the ability to handle a wide range of solid dose forms.
Increased friability may cause issues with machinery
Mini-tabs tend to be more prone to chipping, abrasion and breakage than larger tablets. This is in part because a greater proportion of the tablet is exposed as surface area, but also because it is harder to achieve structural integrity within such a small size.
As well as leading to unnecessarily rejected batches, broken mini-tabs can cause some machines to fail and require time-consuming cleaning before operation can resume. This is not just a problem for process machinery; in quality control, it is essential that automated weighing machines are resilient against fragments and dust and can also distinguish broken tablets within a batch.
Other considerations
With a high surface area and low weight, mini-tabs can develop significant static charge. In some situations this may be problematic as they attract more airborne contaminants, so necessitating containment solutions which make manual weighing particularly difficult.
Static charge can also prevent mini-tabs moving properly through some handling equipment. From a QC perspective it is particularly important that automated checking and weighing machines are able to separate out the individuals and weigh them correctly in these circumstances.
Conclusions
Mini-tabs can represent a substantial opportunity for pharmaceutical research and manufacturing organisations. However, the challenges of precision weighing are substantial. At CI Precision we are a long-established provider of precision weighing solutions for the pharmaceutical industry. Our machines perform extremely well with mini-tabs and provide outstanding ROI.
Please read more about our precision weighing machines at www.ciprecision.com or contact us at www.ciprecision.com/contact to discuss how we could help.
