Development of a Design Space for a Unit Operation: Illustration Using Compression-Mix Blending Process for the Manufacture of a Tablet Dosage Form

Kapsi, Shiva G.; Castro, Lan D.; Muller, Francis X.; Wrzosek, Thomas J.

doi:10.1007/s12247-012-9122-1

Cited by 9 publications

(1 citation statement)

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“…The orthogonal design space for a unit operation is more feasible than the one that is mathematically expressed, and makes it simple for manufacturing process control. Actually, if creating an orthogonal space dose not significantly narrow the design space, then an orthogonal design space can be proposed (32). As a large part of the desirable parameter ranges has been covered ( Fig.…”

Section: Discussionmentioning

confidence: 99%

Application of Quality by Design to the Process Development of Botanical Drug Products: A Case Study

et al. 2013

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This paper was designed to assess the value of quality by design (QbD) to improve the manufacturing process understanding of botanical drug products. Ethanol precipitation, a widely used unit operation in the manufacture of botanical drug products was employed to illustrate the use of QbD, taking the process of danshen (the dry root of Salvia miltiorrhiza Bunge) as an example. The recovery of four active pharmaceutical ingredients (APIs) and the removal of saccharides were used to represent the performance of ethanol precipitation. Potentially critical variables, including density of concentrate, ethanol consumption, and settling temperature were identified through risk assessment methods. Design of experiments (DOE) was used to evaluate the effects of the potentially critical factors on the performance of ethanol precipitation. It was observed that higher density of concentrate leads to higher removal of saccharides, but results in lower recovery of APIs. With the rise of ethanol consumption, the recovery of different APIs behaves in different ways. A potential design space of ethanol precipitation operation was established through DOE studies. The results in this work facilitate the enhanced understanding of the relationships between multiple factors (material attributes and process parameters) and the performance of ethanol precipitation. This case study demonstrated that QbD is a powerful tool to develop manufacturing process of botanical drug products.

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Section: Discussionmentioning

confidence: 99%