With tablet splitting gaining greater attention from FDA and other regulators, what will be the challenges for tablet manufacturers?
The challenge for pharmaceutical tablet manufacturers with the advent of the new regulations is to prove that their products
meet or exceed the proposed requirements. This challenge can only be met by custom designing formulation and tablet tooling
to meet the enhanced testing required of split-tablet segments following tablet breakage. For those manufacturers desirous
of labelling a product as 'functionally scored,' the new regulations will require additional diligence during product development,
the generation of appropriate data to provide regulators with the confidence to approve the 'functionally scored' tablet,
and continued enhanced testing after approval to demonstrate that the 'functionally scored' product continues, in commercial
manufacture, to meet the required specifications.
Nearly half of all Americans aged 55 and above are taking at least one prescription drug, and 25% of those above 55 are taking
four or more prescription drugs. The elderly demographic as a whole is responsible for approximately 30% of prescriptions
filled in the US. The need for dose flexibility, especially within this demographic, is indisputable. We recognized a paradox
in the pharmaceutical industry: while dose flexibility is clearly important, most manufacturers were not commercializing dosage
forms that enabled easy and accurate dose adjustment. The vast majority (estimated to be greater than 85%) of oral dosage
forms were marketed as either unscored tablets or capsules. Many of the remaining scored tablets often bear a cosmetic score
that indicates the middle of the tablet, but that score has proven to be poorly functioning.
The European Union recognized the need for functional scoring over a decade ago and implemented the European Pharmacopeia's
Monograph 0478. In the US, the need for the efficacious and consistent scoring of tablets has recently come into sharp focus
with the USP's publication of Pharmacopeial Standards for the Subdivision Characteristics of Scored Tablets, and the FDA's guideline titled Guidance for Industry, Tablet Scoring: Nomenclature, Labeling, and Data Evaluation.
Our Accu-Break technologies were designed to create dosage forms that could be subdivided easily by hand into exact smaller
doses. In developing the various technologies, we focused on adhering to the following parameters for our tablets:
- The tablets must split into exact partial doses, including ¼ doses if desired.
- The partial doses must pass content uniformity.
- The tablets must be easy to break by patients.
- The tablets and partial doses must pass friability, dissolution, and stability tests.
- The intact tablet must be swallowable (i.e., not too large).
- The unit production cost per tablet must be comparable to conventional tablets.
- Controlled-release formulations and film-coating must be an option.
We have developed two distinct multilayer-tablet technologies, known as 'Accu-B' and 'Accu-T,' both of which incorporate a
strategic drug-free layer that serves as a break layer within the tablets.
With the Accu-B technology, the dosage form has two layers, one of which is drug-free. The second layer contains drug and
is deeply scored. The drug-free layer provides several unique features: first and foremost, given the deep score in the drug
layer, the drug-free layer forms a backbone that gives the finished dosage form mechanical strength to withstand packaging
and shipping operations. Secondly, the drug-free layer is the fracture plane for the Accu-B tablet. The tablet can be broken
through the score, and the fracture occurs in the drug-free layer. Compared with a conventionally scored tablet, the Accu-B
bilayer design ensures partial dosing accuracy and eliminates concerns over loss of mass. The scored tablets can also satisfy
the testing and data requirements for both the EP's Monograph 0478 and the FDA's new scored tablet guidance.
Our Accu-T technology uses up to five layers in a taller-than-wide tablet, and the incorporation of drug-free layers serve
one of two purposes:
A drug-free breaking layer is incorporated into the middle of an Accu-T tablet and is used to separate the drug-containing
layers. Since the drug-containing layers are physically located at the 'top' and 'bottom' of this taller-than-wide tablet,
breaking the tablet through the middle placebo layer separates the dose into exact halves.
The drug-free layer provides a physical barrier between active ingredients. This barrier allows the formulation of incompatible
actives with no worries about co-mixing and resultant physical or chemical stability issues. The technology utilizes machinery
that can produce tablets with up to five compressed layers so the use of more than one drug-free layer can facilitate a 'poly
pill' with three different API-containing formulations.
1. Freeman Technology, Blending white paper, http://www.freemantech.co.uk/en/literature-and-downloads/articles-and-white-papers.html#white-papers