A Quality by Experimental Design Approach to Assess the Effect of Formulation and Process Variables on the Extrusion and Spheronization of Drug-Loaded Pellets Containing Polyplasdone® XL-10

Abstract

Abstract. Successful pellet production has been reported in literature with cross-linked poly(vinylpyrrolidone), Polyplasdone ® XL-10 and INF-10. In the present study, a quality by experimental design approach was used to assess several formulation and process parameter effects on the characteristics of Polyplasdone ® XL-10 pellets, including pellet size, shape, yield, usable yield, friability, and number of fines. The hypothesis is that design of experiments and appropriate data analysis allow optimization of the Polyplasdone product. High drug loading was achieved using caffeine, a moderately soluble drug to allow in vitro release studies. A five-factor, two-level, half-fractional factorial design (Resolution V) with center point batches allowed mathematical modeling of the influence of the factors and their two-factor interactions on five of the responses. The five factors were Polyplasdone ® level in the powder blend, volume of water in the wet massing step, wet mixing time, spheronizer speed, and spheronization time. Each factor and/or its two-factor interaction with another factor influenced pellet characteristics. The behavior of these materials under various processing conditions and component levels during extrusionspheronization have been assessed, discussed, and explained based on the results. Numerical optimization with a desirability of 0.974 was possible because curvature and lack of fit were not significant with any of the model equations. The values predicted by the optimization described well the observed responses. The hypothesis was thus supported.

An Outline of Variables in Pelletization by Extrusion and Spheronization

“…A more extended spheronization time with the lower spheronizer speed provides a suitable environment, resulting in an improved total yield of pellets. A more spheronization time at low spheronizer speed allows moist extrudate particles to aggregate with fine particles and decreases the loss of fine particles from the spheronizer [20]. Hardness, roundness, porosity, bulk densities, tapped densities, friability, flow rate and surface structure of the pellets were also influenced by a change in the spheronization speed [21].…”

Efficient surrogates construction of chemical processes: Case studies on pressure swing adsorption and gas‐to‐liquids

“…Data‐driven surrogates can represent the original physical models by building relationship between inputs and outputs (responses). For some complex systems, there are even no physical models available, and thus surrogates together with the design of experiments (DoEs) seem to be the only choice 5–7 . Surrogates are cheap‐to‐evaluate and can directly be employed for optimization, control, and design in many engineering fields, for example, chemical engineering, 8–11 pharmaceutical manufacturing, 12 supply chain management, 13,14 and aerospace engineering 15–17 …”