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Anastasiya Zakhvatayeva

My publications


Zakhvatayeva A., Zhong W., Makroo H.A., Hare C., Wu C. (2018) An experimental study of die filling of pharmaceutical powders using a rotary die filling system,International Journal of Pharmaceutics553(1-2)pp. 84-96 Elsevier
Die filling is a critical process step in pharmaceutical tablet manufacturing. Mass and content uniformity of the tablets as well as production throughput depend upon the die filling performance of the formulations. The efficiency of the die filling process is influenced by powder properties, such as flowability, cohesion, particle size and morphology, as well as the process conditions. It is hence important to understand the influence of powder properties on the die filling performance. The purpose of the present study is to identify the critical material attributes that determine the efficiency of die filling. For this purpose, a model rotary die filling system was developed to mimic the die filling process in a typical rotary tablet press. The system consists of a round die table of 500/mm diameter, equipped with a rectangular die. The die table can rotate at an equivalent translational velocity of up to 1.5/m/s. The filling occurs when the die passes through a stationary shoe positioned above the die table. Using this system, die filling behaviours of 7 commonly used pharmaceutical excipients with various material characteristics (e.g. particle size distribution, sphericity and morphology) and flow properties were examined. The efficiency of die filling is evaluated using the concept of critical filling velocity. It was found that the critical filling velocity is strongly dependent on such properties as cohesion, flowability, average particle size and air sensitivity index. In particular, the critical filling velocity increases proportionally as the mean particle size, flow function, air permeability and air sensitivity index increase, while it decreases with the increase of specific energy and cohesion.
Zakhvatayeva Anastasiya, Hare Colin, Wu Chuan-Yu (2019) Suction filling of pharmaceutical powders,Powder Technology Elsevier
Die filling is an important process step in manufacturing of tablets. An important mechanism in the die filling process is suction that is developed with the downward motion of the bottom punch once the die is covered by powder. However, the contribution of suction to the die filling performance is still poorly understood. Hence, the present study aimed to experimentally investigate the flow behaviour of powders during suction filling. Four different types of pharmaceutical powders were used and a model suction filling system was developed. Effects of filling and suction velocities, as well as powder properties, on the efficiency of die filling were systematically investigated. Cohesive and free-flowing powders behaved differently at various filling-to-suction velocity ratios. The filling behaviour of cohesive powders was improved at high filling-to-suction ratios due to acceleration-induced densification. Free-flowing powders performed better at low filling-to suction ratios.
Zakhvatayeva A., Hare C., Wu C.Y. (2019) Size-induced segregation during die filling,International Journal of Pharmaceutics: X1100032 Elsevier B V
The present study investigated particle size-induced segregation during die filling of binary pharmaceutical blends, consisting of fine and coarse particles in various fractions. Coarse fraction was made of milled and sieved acetylsalicylic acid, whereas the fine fraction was mannitol. The die filling process was carried out in gravity filling and suction filling. The segregation was assessed through determination of the coarse component concentration using UV?Visible spectrophotometry. The obtained values of concentration, determined for ten units of identical volume inside the die, were used to calculate the segregation index (SI), which was an indicator of uniformity of the powder blend deposited into the die. It was found that high segregation tendency was generally observed during gravity filling at a low velocity, due to the effect of air drag, and during gravity filling at a high velocity, as it was carried out through three consecutive filling steps. The lowest segregation tendency was generally observed during suction filling at a low velocity. The horizontal segregation was mostly observed in the top layers of the die, due to mainly two mechanisms: coarse particles cascading down the heap formed by the powder in the final steps of die filling, which produces higher coarse concentration at the near side of the die, observed at low coarse concentration; or coarse particle cascading down the top surface of the flowing powder stream into the die, which increases the coarse concentration at the far end of the die.