Dr. Sinka's Talk

Aug 20, 2009 - 17:00

Aug 20, 2009 - 18:30

Creativity Hall (Room No. 118)

Seminars

Dr. Csaba Sinka University of Leicester UK

Abstract: 80% of all medication is delivered in tablet form. Tablets are manufactured by compacting a powder blend. The development of a pharmaceutical formulation involves formulation design (e.g. choosing the composition of the powder blend) and process development (e.g. selection of manufacturing processes and equipment) so that the final tablet has the required bioavailability and that the manufacturing processes are robust. The simplest manufacturing process includes a mixing operation and a compaction stage although additional processes are often necessary. In this talk we focus on the scientific challenges involved in the compaction stage. Tablets are made using high speed rotary presses where one machine can produce in excess of 1 million tablets/hour. The process comprises of filling a die with powder compaction in a die using rigid punches and ejection from the die which take place within a few milliseconds. Tablets have tight requirements in terms of bioavailability of drug weight uniformity content uniformity chemical and physical stability mechanical integrity etc. The challenges in achieving these quality criteria are discussed while considering that the manufacturing processes must be robust scaleable transferable and of low cost. The operation cycle of the rotary tablet press presents a rich range powder flow and densification mechanisms with unique features. Powder flow for example has been studied extensively in the context of hopper design however in die fill the material is discharged into a closed cavity where the air pressure is increased as more and more material is deposited. Using high speed video we observe and discuss the dynamic processes created by the interplay between the granular skeleton and air for a range of die fill mechanisms characteristic to single station and rotary tablet presses. Then we examine the process of powder compaction from a continuum mechanics point of view.The challenge in this area is to develop appropriate constitutive models that capture the evolution of the material as it is densified from a loose powder state into a dense compact. We present experimental characterisation methods for model calibration as well review the state of the art in modelling of powder compaction. We discuss the implementation of classic incremental plasticity models as well as the development of deformation plasticity models for practical loading cycles. The coupling between the deformation of the powder aggregate and compression of air in the pore space as well as a coupled thermo-mechanical analysis are presented. The application of the models in formulation design and process development is presented using a range of case studies centred on the density distribution in simple and complex solid dosage forms. Finally we discuss strategies for the development of an integrated approach for modelling the full suite of processes involved in tablet manufacturing such as mixing granulation drying milling handling compression coating and packaging with focus on meeting the required quality attributes of the final product.