Snapshots of Doctoral Research at University College Cork 2011 Manufacturing challenges in the production of high quality modified-release tablets Denis Ring School of Engineering, UCC Knowledge is the only instrument of production that is not subject to diminishing returns (John Maurice Clarke) Introduction The pharmaceutical industry is obliged and regulated to ensure that manufactured medicines (i.e., tablets) meet the highest quality standards. However, no system is perfect. The Euro- pean Medicines Agency (EMEA) state that somewhere between 5-10% of pharmaceutical production batches must be either reworked or discarded, because they do not fully meet the stringent final quality specifications. Poor production quality, often due to inflexible manufacturing and insufficient process understanding represents an unnecessary burden in both time and expense. According to Cedar Management Consulting, the bulk of the global top 16 pharmaceutical companies’ budgets are spent on manufacturing (~36%), whereas the research and development (R&D) expenses (often considered to be the major cost burden) can be less than half of this (~16%). Therefore, there is great interest in making manufacturing more effective and optimising processes in order to deliver consis- tent high quality. Research objective The goal of this research is to facilitate greater process/production understanding and knowledge through the systematic evaluation of the manufacture of a modified-release (MR) oral tablet. The active ingredient in the MR tablet investigated in this research, along with many of the more recently developed drugs, exhibits low solubility, which pro- vides additional challenges for consistent drug release and absorption. Pharmaceutical oral tablets remain the most popular drug delivery mechanism. MR tablets are principally used when the duration of action of a short-acting drug needs to be prolonged. Pharma- ceutical companies also reinvent existing drugs by creating modified-release versions, as a legitimate means of patent extension, thus protecting their product and income integrity. The simplest method for modified-release in oral tablets is a matrix delivery system which incorporates hydrophilic polymers (hypromellose) that swells in the presence of water to 193