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Coated particles or pellets?  Matrix pellets?  Filled into capsules, or compressed into tablets?  Coated tablets?  Matrix tablets?  Orally disintegrating tablets?  A variety of alternatives for modified release solid dosage forms, indeed!  Glatt Pharmaceutical Services’s team of scientists has experience in all of these areas, using our proprietary and conventional technologies. 
 
The patented HS Wurster is a platform technology, not only for pellet and particle coating, but also for drug pellet formation via solution or suspension layering.  Applications include taste masking, coating for enteric properties or for sustained release, or simply for protection against light or moisture.  Particle sizes range from 100 microns to more than a millimeter.  
 
Pellets produced for compression into tablets must be robust ‘to the core’.  Compression often deforms them, causing cracks in the film, or destruction of the pellets, dramatically altering their release properties.  Where possible, Cellets (micro-crystalline cellulose cores) are used as a core material due to their superior hardness.  Final pellet size is also an issue, and for potent pellets, a very small core must be used.  Cellets as small as 100-200 microns in size are selected for drug layering and film coating, with final pellet size a mere 300-400 microns.  The HS Wurster is, again, an excellent choice for applying both the drug layer and film coating.
 
A modified form of the Wurster system has been developed specifically for tablet coating, and is the recipient of 5 US patents.  A fiber scope and high speed camera were used to visually characterize the flow properties of tablets in the Wurster, and to identify problematic areas which include regions of slow or no flow.  These areas typically result in poor distribution uniformity of either applied films or active materials.  Additionally, areas of high velocity impact between the machine components and the tablets were identified and prototypes produced to correct these problems.  Test results include the absence of thinly coated or uncoated tablets, good distribution uniformity, and the tablet hardness requirement reduced to 10 kP for tablets weighing 400 mg.
 
The recently introduced CPS™ system can produce placebo or active loaded pellets in a wide range of sizes.  For oral suspensions, or orally disintegrating tablets, final pellet size is generally limited to 100-200 microns.  For compression into a more traditional tablet, the threshold is approximately 400 microns to assure content uniformity.  Properties of the pellet may be altered by the addition of pH controlling agents or modified release polymers.  In some cases, uncoated pellets produced by the CPS™ system have been compressed into tablets and yielded sustained release properties, including zero-order.
 
The variety of modified release dosage forms requires creativity in formulation and processing.  The assortment of process techniques available to the development staff at Glatt Pharmaceutical Services has allowed us to achieve our goals with a minimum of time and effort.
Is it scale-able?  This is a frequently asked question, often from a formulator who has successfully developed a product on the bench, and is now responsible for shepherding it into pilot and commercial scale equipment.  The answer is sometimes not comforting - it depends!  It is reasonable to expect that as machines and batch size increase, that there may be an impact: spray nozzle considerations, mass effects, etc., may lead to somewhat different behaviour than initially anticipated.  However, with a good understanding of the process, supported by data acquired using DOE (design of experiments), it is possible to develop a robust product, which will yield a reproducible process at the production scale.
 
Evaluation of a process in large equipment should include a number of steps. Fluidization air flow is a key variable for productivity - in general, the higher it is, the faster the spray rate may be when using either water or organic solvent based systems.  Glatt’s Wurster HS systems are designed with interchangeable bottom plates so that the up bed and down bed behaviours may be treated independently.  For dense or tacky substrates and films, a comparatively permeable down bed plate would be selected.  For small or free flowing materials, it would be  less permeable.  With this type of flexibility, it is prudent to conduct a ‘mass-flow’ study - examine the bed behaviour at a variety of process air volumes, and partition heights using several iterations of orifice plates.  Once satisfied, this value is used for the duration of the scale-up activity.  Major process variables such as spray rate, atomizing air pressure (and/or volume), and product temperature are related to the increase in drying capacity and laboratory experience at the small scale (influence on product properties must be well known). 
 
A recent Tech Transfer for a sustained release product  into a 32" HS Wurster yielded encouraging results - some degree of variation in batch size (target +/- 8%) did not impact dissolution; for replicate batches, the dissolution profiles were nearly identical; productivity was nearly doubled and the amount of agglomerates per batch averaged less than 10 g.  When the question “is it scalable?” is asked about the Wurster HS process, the answer is a resounding ‘yes’.  But then again, it depends on the robustness of the formulated product.